Array ( [0] => {{short description|Hormone and medication}} [1] => {{About|the natural hormone|this substance when used as a medication|Epinephrine (medication)||Adrenaline (disambiguation)}} [2] => {{Use dmy dates|date=April 2020}} [3] => {{cs1 config|name-list-style=vanc|display-authors=6}} [4] => {{trim|{{#section:Epinephrine (medication)|Drugbox}}}} [5] => [6] => '''Adrenaline''', also known as '''epinephrine''', is a [[hormone]] and [[Epinephrine (medication)|medication]]{{cite book | vauthors = Lieberman M, Marks A, Peet A | title=Marks' Basic Medical Biochemistry: A Clinical Approach | date = 2013 | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | isbn = 9781608315727 | page = 175 | edition = 4th | url = https://books.google.com/books?id=3FNYdShrCwIC&pg=PA175 }}{{cite web |url= http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=479|title=Adrenaline|date=21 August 2015 }} which is involved in regulating visceral functions (e.g., respiration).{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York, USA | isbn = 9780071481274 | page = 157 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin | quote = Epinephrine occurs in only a small number of central neurons, all located in the medulla. Epinephrine is involved in visceral functions, such as the control of respiration. It is also produced by the adrenal medulla.}} It appears as a white microcrystalline granule.{{cite book | vauthors = Larrañaga M |title=Hawley's Condensed Chemical Dictionary |date=2016 |publisher=John Wiley & Sons, Incorporated |location=New Jersey |page=561}} Adrenaline is normally produced by the [[adrenal gland]]s and by a small number of [[neurons]] in the [[medulla oblongata]].{{Cite web |title=Adrenaline: physiology and pharmacology {{!}} DermNet |url=https://dermnetnz.org/topics/the-physiology-and-pharmacology-of-adrenaline |access-date=2023-03-20 |website=dermnetnz.org}} It plays an essential role in the [[fight-or-flight response]] by increasing blood flow to muscles, [[Cardiac output|heart output]] by acting on the [[SA node]],{{cite journal | vauthors = Brown HF, DiFrancesco D, Noble SJ | title = How does adrenaline accelerate the heart? | journal = Nature | volume = 280 | issue = 5719 | pages = 235–236 | date = July 1979 | pmid = 450140 | doi = 10.1038/280235a0 | s2cid = 4350616 | bibcode = 1979Natur.280..235B }} [[Pupillary response|pupil dilation response]], and [[blood sugar level]].{{cite book | vauthors = Bell DR | title=Medical physiology : principles for clinical medicine|date=2009|publisher=Lippincott Williams & Wilkins|location=Philadelphia|isbn=9780781768528|page=312|edition=3rd|url=https://books.google.com/books?id=tBeAeYS-vRUC&pg=PA312}} It does this by binding to [[alpha receptor|alpha]] and [[beta receptors]].{{cite book| vauthors = Khurana I |title=Essentials of Medical Physiology|date=2008|publisher=Elsevier India|isbn=9788131215661|page=460|url=https://books.google.com/books?id=Cm_kLhU1AP0C&pg=PA460}} It is found in many animals, including humans, and some [[Protozoa|single-celled organisms]].{{cite book| vauthors = Buckley E |title=Venomous Animals and Their Venoms: Venomous Vertebrates|date=2013|publisher=Elsevier|isbn=9781483262888|page=478|url=https://books.google.com/books?id=3SrLBAAAQBAJ&pg=PA478}}{{cite book|title=Animal Physiology: Adaptation and Environment|date=1997|publisher=Cambridge University Press|isbn=9781107268500|page=510|edition=5th|url=https://books.google.com/books?id=hcw2AAAAQBAJ&pg=PA510}} It has also been isolated from the plant ''[[Scoparia dulcis]]'' found in Northern Vietnam.{{cite journal | vauthors = Phan MG, Phan TS, Matsunami K, Otsuka H | title = Chemical and biological evaluation on scopadulane-type diterpenoids from Scoparia dulcis of Vietnamese origin | journal = Chemical & Pharmaceutical Bulletin | volume = 54 | issue = 4 | pages = 546–549 | date = April 2006 | pmid = 16595962 | doi = 10.1248/cpb.54.546 | doi-access = free }} [7] => [8] => ==Medical uses== [9] => {{Main|Epinephrine (medication)}} [10] => [11] => As a medication, it is used to treat several conditions, including [[Allergy|allergic reaction]] [[anaphylaxis]], [[cardiac arrest]], and superficial bleeding.{{cite web|title=Epinephrine|url=https://www.drugs.com/monograph/epinephrine.html|work=The American Society of Health-System Pharmacists|access-date=15 August 2015}} [[nebulizer|Inhaled]] adrenaline may be used to improve the symptoms of [[croup]].{{cite journal | vauthors = Everard ML | title = Acute bronchiolitis and croup | journal = Pediatric Clinics of North America | volume = 56 | issue = 1 | pages = 119–133, x–xi | date = February 2009 | pmid = 19135584 | doi = 10.1016/j.pcl.2008.10.007 }} It may also be used for [[asthma]] when other treatments are not effective. It is given [[intravenously]], by [[Intramuscular injection|injection into a muscle]], by inhalation, or by [[Subcutaneous injection|injection just under the skin]]. Common side effects include shakiness, [[anxiety (mood)|anxiety]], and sweating. A fast heart rate and high blood pressure may occur. Occasionally it may result in an [[Arrhythmia|abnormal heart rhythm]]. While the safety of its use during [[pregnancy]] and [[breastfeeding]] is unclear, the benefits to the mother must be taken into account. [12] => [13] => A case has been made for the use of adrenaline infusion in place of the widely accepted treatment of [[inotrope]]s for preterm infants with clinical cardiovascular compromise. Although sufficient data strongly recommends adrenaline infusions as a viable treatment, more trials are needed to conclusively determine that these infusions will successfully reduce [[morbidity]] and [[Mortality rate|mortality]] rates among preterm, cardiovascularly compromised infants.{{cite journal | vauthors = Paradisis M, Osborn DA | title = Adrenaline for prevention of morbidity and mortality in preterm infants with cardiovascular compromise | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD003958 | date = 2004 | pmid = 14974048 | doi = 10.1002/14651858.CD003958.pub2 }} [14] => [15] => Epinephrine can also be used to treat open-angle glaucoma, as it has been found to lower the outflow of aqueous humor in the eye. This lowers the intraocular pressure in the eye and thus aids in treatment. {{cite journal | vauthors = Erickson-Lamy KA, Nathanson JA | title = Epinephrine increases facility of outflow and cyclic AMP content in the human eye in vitro | journal = Investigative Ophthalmology & Visual Science | volume = 33 | issue = 9 | pages = 2672–2678 | date = August 1992 | pmid = 1353486 | url = https://iovs.arvojournals.org/article.aspx?articleid=2178975 }} [16] => [17] => ==Physiological effects== [18] => The [[adrenal medulla]] is a major contributor to total circulating [[catecholamines]] ([[L-DOPA|L-DOPA]] is at a higher concentration in the [[Blood plasma|plasma]]),{{cite journal | vauthors = Rizzo V, Memmi M, Moratti R, Melzi d'Eril G, Perucca E | title = Concentrations of L-dopa in plasma and plasma ultrafiltrates | journal = Journal of Pharmaceutical and Biomedical Analysis | volume = 14 | issue = 8–10 | pages = 1043–1046 | date = June 1996 | pmid = 8818013 | doi = 10.1016/s0731-7085(96)01753-0 }} though it contributes over 90% of circulating adrenaline. Little adrenaline is found in other tissues, mostly in scattered [[chromaffin cells]] and in a small number of [[neuron]]s that use adrenaline as a [[neurotransmitter]].{{cite journal | vauthors = Fuller RW | title = Pharmacology of brain epinephrine neurons | journal = Annual Review of Pharmacology and Toxicology | volume = 22 | issue = 1 | pages = 31–55 | date = April 1982 | pmid = 6805416 | doi = 10.1146/annurev.pa.22.040182.000335 }} Following [[adrenalectomy]], adrenaline disappears below the detection limit in the bloodstream.{{cite journal | vauthors = Cryer PE | title = Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system | journal = The New England Journal of Medicine | volume = 303 | issue = 8 | pages = 436–444 | date = August 1980 | pmid = 6248784 | doi = 10.1056/nejm198008213030806 }} [19] => [20] => Pharmacological doses of adrenaline stimulate [[Alpha-1 adrenergic receptor|α1]], [[Alpha-2 adrenergic receptor|α2]], [[Beta-1 adrenergic receptor|β1]], [[Beta-2 adrenergic receptor|β2]], and [[Beta-3 adrenergic receptor|β3]] adrenoceptors of the [[sympathetic nervous system]]. Sympathetic nerve receptors are classified as adrenergic, based on their responsiveness to adrenaline.{{cite journal | vauthors = Barger G, Dale HH | title = Chemical structure and sympathomimetic action of amines | journal = The Journal of Physiology | volume = 41 | issue = 1–2 | pages = 19–59 | date = October 1910 | pmid = 16993040 | pmc = 1513032 | doi = 10.1113/jphysiol.1910.sp001392 }} The term "adrenergic" is often misinterpreted in that the main sympathetic neurotransmitter is [[noradrenaline]], rather than adrenaline, as discovered by [[Ulf von Euler]] in 1946.{{cite journal| vauthors = Von Euler US |title=A specific sympathomimetic ergone in adrenergic nerve fibres (sympathin) and its relations to adrenaline and nor adrenaline|journal=Acta Physiologica Scandinavica|year=1946|volume=12|pages=73–97|doi=10.1111/j.1748-1716.1946.tb00368.x}}{{cite journal | vauthors = Von Euler US, Hillarp NA | title = Evidence for the presence of noradrenaline in submicroscopic structures of adrenergic axons | journal = Nature | volume = 177 | issue = 4497 | pages = 44–45 | date = January 1956 | pmid = 13288591 | doi = 10.1038/177044b0 | s2cid = 4214745 | bibcode = 1956Natur.177...44E }} Adrenaline has a β2 adrenoceptor-mediated effect on [[metabolism]] and the [[airway]], with no direct neural connection from the [[sympathetic ganglia]] to the [[airway]].{{cite journal | vauthors = Warren J | title = The adrenal medulla and the airway | journal = British Journal of Diseases of the Chest | volume = 80 | issue = 1 | pages = 1–6 | date = January 1986 | pmid = 3004549 | doi = 10.1016/0007-0971(86)90002-1 }}{{cite journal | vauthors = Twentyman OP, Disley A, Gribbin HR, Alberti KG, Tattersfield AE | title = Effect of beta-adrenergic blockade on respiratory and metabolic responses to exercise | journal = Journal of Applied Physiology | volume = 51 | issue = 4 | pages = 788–793 | date = October 1981 | pmid = 6795164 | doi = 10.1152/jappl.1981.51.4.788 }}{{cite journal | vauthors = Richter EA, Galbo H, Christensen NJ | title = Control of exercise-induced muscular glycogenolysis by adrenal medullary hormones in rats | journal = Journal of Applied Physiology | volume = 50 | issue = 1 | pages = 21–26 | date = January 1981 | pmid = 7009527 | doi = 10.1152/jappl.1981.50.1.21 | publisher = [[American Physiological Society]] }} [21] => [22] => [[Walter Bradford Cannon]] originally proposed the concept of the adrenal medulla and the [[sympathetic nervous system]] being involved in the flight, fight, and fright response.{{cite journal| vauthors = Canon WB |title=Studies on the conditions of activity in endocrine organs xxvii. Evidence that medulliadrenal secretion is not continuous|journal=The American Journal of Physiology|year=1931|volume=98|pages=447–453|doi=10.1152/ajplegacy.1931.98.3.447}} But the adrenal medulla, in contrast to the adrenal cortex, is not required for survival. In adrenalectomized patients, hemodynamic and metabolic responses to stimuli such as hypoglycemia and exercise remain normal.{{cite journal | vauthors = Cryer PE, Tse TF, Clutter WE, Shah SD | title = Roles of glucagon and epinephrine in hypoglycemic and nonhypoglycemic glucose counterregulation in humans | journal = The American Journal of Physiology | volume = 247 | issue = 2 Pt 1 | pages = E198–E205 | date = August 1984 | pmid = 6147094 | doi = 10.1152/ajpendo.1984.247.2.E198 }}{{cite journal | vauthors = Hoelzer DR, Dalsky GP, Schwartz NS, Clutter WE, Shah SD, Holloszy JO, Cryer PE | title = Epinephrine is not critical to prevention of hypoglycemia during exercise in humans | journal = The American Journal of Physiology | volume = 251 | issue = 1 Pt 1 | pages = E104–E110 | date = July 1986 | pmid = 3524257 | doi = 10.1152/ajpendo.1986.251.1.E104 }} [23] => [24] => ===Exercise=== [25] => One physiological stimulus to adrenaline secretion is exercise. This was first demonstrated by measuring the dilation of a (denervated) pupil of a cat on a treadmill,{{cite journal | vauthors = Hartman FA, Waite RH, McCordock HA | title = The liberation of epinephrine during muscular exercise|journal=The American Journal of Physiology|year=1922|volume=62| issue = 2|pages=225–241| doi = 10.1152/ajplegacy.1922.62.2.225}} later confirmed using a biological assay of urine samples.{{cite journal | vauthors = Von Euler US, Hellner S | title = Excretion of noradrenaline and adrenaline in muscular work | journal = Acta Physiologica Scandinavica | volume = 26 | issue = 2–3 | pages = 183–191 | date = September 1952 | pmid = 12985406 | doi = 10.1111/j.1748-1716.1952.tb00900.x }} Biochemical methods for measuring catecholamines in plasma were published from 1950 onwards.{{cite journal | vauthors = Lund A | title = Simultaneous fluorimetric determinations of adrenaline and noradrenaline in blood | journal = Acta Pharmacologica et Toxicologica | volume = 6 | issue = 2 | pages = 137–146 | year = 1950 | pmid = 24537959 | doi = 10.1111/j.1600-0773.1950.tb03460.x }} Although much valuable work has been published using fluorimetric assays to measure total catecholamine concentrations, the method is too non-specific and insensitive to accurately determine the very small quantities of adrenaline in plasma. The development of extraction methods and enzyme–isotope derivate radio-enzymatic assays (REA) transformed the analysis down to a sensitivity of 1 pg for adrenaline.{{cite journal | vauthors = Johnson GA, Kupiecki RM, Baker CA | title = Single isotope derivative (radioenzymatic) methods in the measurement of catecholamines | journal = Metabolism | volume = 29 | issue = 11 Suppl 1 | pages = 1106–1113 | date = November 1980 | pmid = 7001177 | doi = 10.1016/0026-0495(80)90018-9 }} Early REA plasma assays indicated that adrenaline and total catecholamines rise late in exercise, mostly when anaerobic metabolism commences.{{cite journal | vauthors = Galbo H, Holst JJ, Christensen NJ | title = Glucagon and plasma catecholamine responses to graded and prolonged exercise in man | journal = Journal of Applied Physiology | volume = 38 | issue = 1 | pages = 70–76 | date = January 1975 | pmid = 1110246 | doi = 10.1152/jappl.1975.38.1.70 }}{{cite journal | vauthors = Winder WW, Hagberg JM, Hickson RC, Ehsani AA, McLane JA | title = Time course of sympathoadrenal adaptation to endurance exercise training in man | journal = Journal of Applied Physiology | volume = 45 | issue = 3 | pages = 370–374 | date = September 1978 | pmid = 701121 | doi = 10.1152/jappl.1978.45.3.370 }}{{cite journal | vauthors = Kindermann W, Schnabel A, Schmitt WM, Biro G, Hippchen M | title = [Catecholamines, GH, cortisol, glucagon, insulin, and sex hormones in exercise and beta 1-blockade (author's transl)] | journal = Klinische Wochenschrift | volume = 60 | issue = 10 | pages = 505–512 | date = May 1982 | pmid = 6124653 | doi = 10.1007/bf01756096 | s2cid = 30270788 }} [26] => [27] => During exercise, the adrenaline blood concentration rises partially from the increased secretion of the adrenal medulla and partly from the decreased metabolism of adrenaline due to reduced blood flow to the liver.{{cite journal | vauthors = Warren JB, Dalton N, Turner C, Clark TJ, Toseland PA | title = Adrenaline secretion during exercise | journal = Clinical Science | volume = 66 | issue = 1 | pages = 87–90 | date = January 1984 | pmid = 6690194 | doi = 10.1042/cs0660087 }} Infusion of adrenaline to reproduce exercise circulating concentrations of adrenaline in subjects at rest has little hemodynamic effect other than a slight β2-mediated fall in diastolic blood pressure.{{cite journal | vauthors = Fitzgerald GA, Barnes P, Hamilton CA, Dollery CT | title = Circulating adrenaline and blood pressure: the metabolic effects and kinetics of infused adrenaline in man | journal = European Journal of Clinical Investigation | volume = 10 | issue = 5 | pages = 401–406 | date = October 1980 | pmid = 6777175 | doi = 10.1111/j.1365-2362.1980.tb00052.x | s2cid = 38894042 }}{{cite journal | vauthors = Warren JB, Dalton N | title = A comparison of the bronchodilator and vasopressor effects of exercise levels of adrenaline in man | journal = Clinical Science | volume = 64 | issue = 5 | pages = 475–479 | date = May 1983 | pmid = 6831836 | doi = 10.1042/cs0640475 }} Infusion of adrenaline well within the physiological range suppresses human airway hyper-reactivity sufficiently to antagonize the constrictor effects of inhaled histamine.{{cite journal | vauthors = Warren JB, Dalton N, Turner C, Clark TJ | title = Protective effect of circulating epinephrine within the physiologic range on the airway response to inhaled histamine in nonasthmatic subjects | journal = The Journal of Allergy and Clinical Immunology | volume = 74 | issue = 5 | pages = 683–686 | date = November 1984 | pmid = 6389647 | doi = 10.1016/0091-6749(84)90230-6 | doi-access = free }} [28] => [29] => A link between the sympathetic nervous system and the lungs was shown in 1887 when Grossman showed that stimulation of cardiac accelerator nerves reversed muscarine-induced airway constriction.{{cite journal| vauthors = Grossman M |title=Das muscarin-lungen-odem |journal=Zeitschrift für klinische Medizin|year=1887|volume=12|pages=550–591}} In experiments in the dog, where the sympathetic chain was cut at the level of the diaphragm, Jackson showed that there was no direct sympathetic innervation to the lung, but bronchoconstriction was reversed by the release of adrenaline from the adrenal medulla.{{cite journal | vauthors= Jackson DE | title = The pulmonary action of the adrenal glands|journal=Journal of Pharmacology and Experimental Therapeutics|year=1912|volume=4|pages=59–74}} An increased incidence of asthma has not been reported for adrenalectomized patients; those with a predisposition to asthma will have some protection from airway hyper-reactivity from their corticosteroid replacement therapy. Exercise induces progressive airway dilation in normal subjects that correlates with workload and is not prevented by beta-blockade.{{cite journal | vauthors = Kagawa J, Kerr HD | title = Effects of brief graded exercise on specific airway conductance in normal subjects | journal = Journal of Applied Physiology | volume = 28 | issue = 2 | pages = 138–144 | date = February 1970 | pmid = 5413299 | doi = 10.1152/jappl.1970.28.2.138 }} The progressive airway dilation with increasing exercise is mediated by a progressive reduction in resting vagal tone. Beta blockade with propranolol causes a rebound in airway resistance after exercise in normal subjects over the same time course as the bronchoconstriction seen with exercise-induced asthma.{{cite journal | vauthors = Warren JB, Jennings SJ, Clark TJ | title = Effect of adrenergic and vagal blockade on the normal human airway response to exercise | journal = Clinical Science | volume = 66 | issue = 1 | pages = 79–85 | date = January 1984 | pmid = 6228370 | doi = 10.1042/cs0660079 }} The reduction in airway resistance during exercise reduces the work of breathing.{{cite journal | vauthors = Jennings SJ, Warren JB, Pride NB | title = Airway caliber and the work of breathing in humans | journal = Journal of Applied Physiology | volume = 63 | issue = 1 | pages = 20–24 | date = July 1987 | pmid = 2957350 | doi = 10.1152/jappl.1987.63.1.20 }} [30] => [31] => ===Emotional responses=== [32] => Every emotional response has a behavioral, an autonomic, and a hormonal component. The hormonal component includes the release of adrenaline, an adrenomedullary response to stress controlled by the [[sympathetic nervous system]]. The major emotion studied in relation to adrenaline is fear. In an experiment, subjects who were injected with adrenaline expressed more negative and fewer positive facial expressions to fear films compared to a control group. These subjects also reported a more intense fear from the films and greater mean intensity of negative memories than control subjects.{{cite journal | vauthors = Mezzacappa ES, Katkin ES, Palmer SN | year = 1999 | title = Epinephrine, arousal, and emotion: A new look at two-factor theory | journal = Cognition and Emotion | volume = 13 | issue = 2| pages = 181–199 | doi = 10.1080/026999399379320}} The findings from this study demonstrate that there are learned associations between negative feelings and levels of adrenaline. Overall, the greater amount of adrenaline is positively correlated with an aroused state of [[negative emotion]]s. These findings can be an effect in part that adrenaline elicits physiological sympathetic responses, including an increased heart rate and knee shaking, which can be attributed to the feeling of fear regardless of the actual level of fear elicited from the video. Although studies have found a definite relation between adrenaline and fear, other emotions have not had such results. In the same study, subjects did not express a greater amusement to an amusement film nor greater anger to an anger film. Similar findings were also supported in a study that involved rodent subjects that either were able or unable to produce adrenaline. Findings support the idea that adrenaline has a role in facilitating the encoding of emotionally arousing events, contributing to higher levels of arousal due to fear.{{cite journal | vauthors = Toth M, Ziegler M, Sun P, Gresack J, Risbrough V | title = Impaired conditioned fear response and startle reactivity in epinephrine-deficient mice | journal = Behavioural Pharmacology | volume = 24 | issue = 1 | pages = 1–9 | date = February 2013 | pmid = 23268986 | pmc = 3558035 | doi = 10.1097/FBP.0b013e32835cf408 }} [33] => [34] => ===Memory=== [35] => It has been found that adrenergic hormones, such as adrenaline, can produce retrograde enhancement of [[long-term memory]] in humans. The release of adrenaline due to emotionally stressful events, which is endogenous adrenaline, can modulate memory consolidation of the events, ensuring memory strength that is proportional to memory importance. Post-learning adrenaline activity also interacts with the degree of arousal associated with the initial coding.{{cite journal | vauthors = Cahill L, Alkire MT | title = Epinephrine enhancement of human memory consolidation: interaction with arousal at encoding | journal = Neurobiology of Learning and Memory | volume = 79 | issue = 2 | pages = 194–198 | date = March 2003 | pmid = 12591227 | doi = 10.1016/S1074-7427(02)00036-9 | s2cid = 12099979 }} There is evidence that suggests adrenaline does have a role in long-term stress adaptation and emotional memory encoding specifically. Adrenaline may also play a role in elevating arousal and fear memory under particular pathological conditions, including [[post-traumatic stress disorder]]. Overall, "Extensive evidence indicates that epinephrine (EPI) modulates memory consolidation for emotionally arousing tasks in animals and human subjects."{{cite journal | vauthors = Dornelles A, de Lima MN, Grazziotin M, Presti-Torres J, Garcia VA, Scalco FS, Roesler R, Schröder N | title = Adrenergic enhancement of consolidation of object recognition memory | journal = Neurobiology of Learning and Memory | volume = 88 | issue = 1 | pages = 137–142 | date = July 2007 | pmid = 17368053 | doi = 10.1016/j.nlm.2007.01.005 | s2cid = 27697668 }} Studies have also found that recognition memory involving adrenaline depends on a mechanism that depends on β adrenoceptors. Adrenaline does not readily cross the blood-brain barrier, so its effects on memory consolidation are at least partly initiated by β adrenoceptors in the periphery. Studies have found that [[sotalol]], a [[Beta blocker|β adrenoceptor antagonist]] that also does not readily enter the brain, blocks the enhancing effects of peripherally administered adrenaline on memory.{{cite journal | vauthors = Roozendaal B, McGaugh JL | title = Memory modulation | journal = Behavioral Neuroscience | volume = 125 | issue = 6 | pages = 797–824 | date = December 2011 | pmid = 22122145 | pmc = 3236701 | doi = 10.1037/a0026187 }} These findings suggest that β adrenoceptors are necessary for adrenaline to have an impact on memory consolidation.{{cite journal | vauthors = Tully K, Bolshakov VY | title = Emotional enhancement of memory: how norepinephrine enables synaptic plasticity | journal = Molecular Brain | volume = 3 | issue = 1 | pages = 15 | date = May 2010 | pmid = 20465834 | pmc = 2877027 | doi = 10.1186/1756-6606-3-15 | doi-access = free }}{{cite journal | vauthors = Ferry B, Roozendaal B, McGaugh JL | title = Basolateral amygdala noradrenergic influences on memory storage are mediated by an interaction between beta- and alpha1-adrenoceptors | journal = The Journal of Neuroscience | volume = 19 | issue = 12 | pages = 5119–5123 | date = June 1999 | pmid = 10366644 | pmc = 6782651 | doi = 10.1523/JNEUROSCI.19-12-05119.1999 }} [36] => [37] => ==Pathology== [38] => Increased adrenaline secretion is observed in [[pheochromocytoma]], [[hypoglycemia]], [[myocardial infarction]], and to a lesser degree, in [[essential tremor]] (also known as benign, familial, or idiopathic tremor). A general increase in sympathetic neural activity is usually accompanied by increased adrenaline secretion, but there is selectivity during hypoxia and hypoglycemia, when the ratio of adrenaline to noradrenaline is considerably increased.{{cite journal | vauthors = Feldberg W, Minz B, Tsudzimura H | title = The mechanism of the nervous discharge of adrenaline | journal = The Journal of Physiology | volume = 81 | issue = 3 | pages = 286–304 | date = June 1934 | pmid = 16994544 | pmc = 1394156 | doi = 10.1113/jphysiol.1934.sp003136 }}{{cite journal | vauthors = Burn JH, Hutcheon DE, Parker RH | title = Adrenaline and noradrenaline in the suprarenal medulla after insulin | journal = British Journal of Pharmacology and Chemotherapy | volume = 5 | issue = 3 | pages = 417–423 | date = September 1950 | pmid = 14777865 | pmc = 1509946 | doi = 10.1111/j.1476-5381.1950.tb00591.x }}{{cite journal | vauthors = Outschoorn AS | title = The hormones of the adrenal medulla and their release | journal = British Journal of Pharmacology and Chemotherapy | volume = 7 | issue = 4 | pages = 605–615 | date = December 1952 | pmid = 13019029 | pmc = 1509311 | doi = 10.1111/j.1476-5381.1952.tb00728.x }} Therefore, there must be some autonomy of the adrenal medulla from the rest of the sympathetic system. [39] => [40] => Myocardial infarction is associated with high levels of circulating adrenaline and noradrenaline, particularly in cardiogenic shock.{{cite journal | vauthors = Benedict CR, Grahame-Smith DG | title = Plasma adrenaline and noradrenaline concentrations and dopamine-beta-hydroxylase activity in myocardial infarction with and without cardiogenic shock | journal = British Heart Journal | volume = 42 | issue = 2 | pages = 214–220 | date = August 1979 | pmid = 486283 | pmc = 482137 | doi = 10.1136/hrt.42.2.214 }}{{cite journal | vauthors = Nadeau RA, de Champlain J | title = Plasma catecholamines in acute myocardial infarction | journal = American Heart Journal | volume = 98 | issue = 5 | pages = 548–554 | date = November 1979 | pmid = 495400 | doi = 10.1016/0002-8703(79)90278-3 }} [41] => [42] => [[Benign familial tremor]] (BFT) is responsive to peripheral β adrenergic blockers, and β2-stimulation is known to cause tremor. Patients with BFT were found to have increased plasma adrenaline but not noradrenaline.{{cite journal | vauthors = Larsson S, Svedmyr N | title = Tremor caused by sympathomimetics is mediated by beta 2-adrenoceptors|journal=Scandinavian Journal of Respiratory Diseases |year=1977|volume=58| issue = 1|pages=5–10| pmid = 190674}}{{cite journal | vauthors = Warren JB, O'Brien M, Dalton N, Turner CT | title = Sympathetic activity in benign familial tremor | journal = Lancet | volume = 1 | issue = 8374 | pages = 461–462 | date = February 1984 | pmid = 6142198 | doi = 10.1016/S0140-6736(84)91804-X | s2cid = 36267406 }} [43] => [44] => Low or absent concentrations of adrenaline can be seen in autonomic neuropathy or following adrenalectomy. Failure of the adrenal cortex, as with [[Addison's disease]], can suppress adrenaline secretion as the activity of the synthesizing enzyme, [[Phenylethanolamine N-methyltransferase|phenylethanolamine-''N''-methyltransferase]], depends on the high concentration of cortisol that drains from the cortex to the medulla.{{cite journal | vauthors = Wurtman RJ, Pohorecky LA, Baliga BS | title = Adrenocortical control of the biosynthesis of epinephrine and proteins in the adrenal medulla | journal = Pharmacological Reviews | volume = 24 | issue = 2 | pages = 411–426 | date = June 1972 | pmid = 4117970 }}{{cite journal | vauthors = Wright A, Jones IC | title = Chromaffin tissue in the lizard adrenal gland | journal = Nature | volume = 175 | issue = 4466 | pages = 1001–1002 | date = June 1955 | pmid = 14394091 | doi = 10.1038/1751001b0 | s2cid = 36742705 | bibcode = 1955Natur.175.1001W }}{{cite journal | vauthors = Coupland RE | title = On the morphology and adrenaline-nor-adrenaline content of chromaffin tissue | journal = The Journal of Endocrinology | volume = 9 | issue = 2 | pages = 194–203 | date = April 1953 | pmid = 13052791 | doi = 10.1677/joe.0.0090194 }} [45] => [46] => ==Terminology== [47] => In 1901, [[Takamine Jōkichi|Jōkichi Takamine]] patented a purified extract from the [[adrenal glands]], which was [[List of generic and genericized trademarks|trademark]]ed by [[Parke-Davis|Parke, Davis & Co]] in the US. The [[British Approved Name]] and ''[[European Pharmacopoeia]]'' term for this drug is hence ''adrenaline'' (from [[Latin]] ''[[wiktionary:ad#Latin|ad]]'', "on", and ''[[wiktionary:renalis#Latin|rēnālis]]'', "of the kidney", from ''[[wiktionary:ren#Latin|ren]]'', "kidney").European Pharmacopoeia 7.0 07/2008:2303 [48] => [49] => However, the pharmacologist [[John Jacob Abel|John Abel]] had already prepared an extract from adrenal glands as early as 1897, and he coined the name ''epinephrine ''to describe it (from [[Ancient Greek]] [[:wikt:ἐπί|ἐπῐ́]] (''epí''), "upon", and [[:wikt:νεφρός|νεφρός]] (''nephrós''), "kidney").{{cite journal | vauthors = Aronson JK | title = "Where name and image meet"—the argument for "adrenaline" | journal = BMJ | volume = 320 | issue = 7233 | pages = 506–509 | date = February 2000 | pmid = 10678871 | pmc = 1127537 | doi = 10.1136/bmj.320.7233.506 }} As the term ''Adrenaline'' was a registered trademark in the US, and in the belief that Abel's extract was the same as Takamine's (a belief since disputed), epinephrine instead became{{when|date=February 2017}} the generic name used in the US and remains the [[pharmaceutical drug|pharmaceutical's]] [[United States Adopted Name]] and [[International Nonproprietary Name]] (though the name adrenaline is frequently used{{cite web | url = https://www.genericides.org/trademark/adrenaline | title = Has adrenaline become a generic trademark? | archive-url = https://web.archive.org/web/20210501125129/https://genericides.org/trademark/adrenaline | archive-date = 1 May 2021 | work = genericides.org }}). [50] => [51] => The terminology is now one of the few differences between the INN and BAN systems of names.{{cite web|url=http://www.mhra.gov.uk/Howweregulate/Medicines/Namingofmedicines/ChangestomedicinesnamesBANstorINNs/index.htm|title=Naming human medicines – GOV.UK|website=www.mhra.gov.uk|date=6 June 2019 }} Although European health professionals and scientists preferentially use the term ''adrenaline'', the converse is true among American health professionals and scientists. Nevertheless, even among the latter, receptors for this substance are called ''adrenergic receptors'' or ''adrenoceptors'', and pharmaceuticals that mimic its effects are often called ''adrenergics''. The history of adrenaline and epinephrine is reviewed by Rao.{{cite journal | vauthors = Rao Y | title = The First Hormone: Adrenaline | journal = Trends in Endocrinology and Metabolism | volume = 30 | issue = 6 | pages = 331–334 | date = June 2019 | pmid = 31064696 | doi = 10.1016/j.tem.2019.03.005 | s2cid = 144207341 }} [52] => [53] => == Mechanism of action == [54] => {{See also|Adrenergic receptor}} [55] => {| class="wikitable" style="float:right; margin:1em" [56] => |+ {{nowrap|Physiologic responses to adrenaline by organ}} [57] => |- [58] => ! Organ [59] => ! Effects [60] => |- [61] => | [[Heart]] [62] => | Increases heart rate; contractility; conduction across AV node [63] => |- [64] => | [[Lung]]s [65] => | Increases respiratory rate; bronchodilation [66] => |- [67] => | [[Liver]] [68] => | Stimulates [[glycogenolysis]] [69] => |- [70] => |[[Muscle]] [71] => | Stimulates glycogenolysis and [[glycolysis]] [72] => |- [73] => | [[Brain]] [74] => | Increased cerebral tissue oxygenation [75] => |- [76] => | Rowspan=3| Systemic [77] => | [[Vasoconstriction]] and [[vasodilation]] [78] => |- [79] => | Triggers [[lipolysis]] [80] => |- [81] => | Muscle contraction [82] => |} [83] => [[File:Fish Melanophores Responding to Adrenaline.webm|thumb|7x speed timelapse video of fish melanophores responding to 200μ[[Molar_concentration|M]] adrenaline]] [84] => As a hormone, adrenaline acts on nearly all body tissues by binding to [[adrenergic receptor]]s. Its effects on various tissues depend on the type of tissue and expression of specific forms of [[adrenergic receptor]]s. For example, high levels of adrenaline cause [[smooth muscle]] relaxation in the airways but causes contraction of the smooth muscle that lines most [[arteriole]]s. [85] => [86] => Adrenaline is a nonselective [[agonist]] of all adrenergic receptors, including the major subtypes [[Alpha-1 adrenergic receptor|α1]], [[Alpha-2 adrenergic receptor|α2]], [[Beta-1 adrenergic receptor|β1]], [[Beta-2 adrenergic receptor|β2]], and [[Beta-3 adrenergic receptor|β3]].{{Cite book | vauthors = Shen H | title=Illustrated Pharmacology Memory Cards: PharMnemonics | year=2008 | publisher=Minireview | isbn=978-1-59541-101-3 | pages=4}} Adrenaline's binding to these receptors triggers a number of metabolic changes. Binding to α-adrenergic receptors inhibits [[insulin]] secretion by the [[pancreas]], stimulates [[glycogenolysis]] in the [[liver]] and [[muscle]],{{cite journal | vauthors = Arnall DA, Marker JC, Conlee RK, Winder WW | title = Effect of infusing epinephrine on liver and muscle glycogenolysis during exercise in rats | journal = The American Journal of Physiology | volume = 250 | issue = 6 Pt 1 | pages = E641–E649 | date = June 1986 | pmid = 3521311 | doi = 10.1152/ajpendo.1986.250.6.E641 }} and stimulates [[glycolysis]] and inhibits insulin-mediated [[glycogenesis]] in muscle.{{cite journal | vauthors = Raz I, Katz A, Spencer MK | title = Epinephrine inhibits insulin-mediated glycogenesis but enhances glycolysis in human skeletal muscle | journal = The American Journal of Physiology | volume = 260 | issue = 3 Pt 1 | pages = E430–E435 | date = March 1991 | pmid = 1900669 | doi = 10.1152/ajpendo.1991.260.3.E430 }}{{cite book | vauthors = Sircar S |title=Medical Physiology |publisher=Thieme Publishing Group |year=2007 |pages=536 |isbn=978-3-13-144061-7 }} β adrenergic receptor binding triggers [[glucagon]] secretion in the pancreas, increased [[adrenocorticotropic hormone]] (ACTH) secretion by the [[pituitary gland]], and increased [[lipolysis]] by [[adipose tissue]]. Together, these effects increase [[blood glucose]] and [[fatty acid]]s, providing substrates for energy production within cells throughout the body. Binding of β adrenergic receptor also increases the production of cyclic AMP.{{cite journal | vauthors = Vasudevan NT, Mohan ML, Goswami SK, Naga Prasad SV | title = Regulation of β-adrenergic receptor function: an emphasis on receptor resensitization | journal = Cell Cycle | volume = 10 | issue = 21 | pages = 3684–3691 | date = November 2011 | pmid = 22041711 | pmc = 3266006 | doi = 10.4161/cc.10.21.18042 }} [87] => [88] => Adrenaline causes [[hepatocyte|liver cells]] to release [[glucose]] into the blood, acting through both alpha and beta-adrenergic receptors to stimulate glycogenolysis. Adrenaline binds to β2 receptors on liver cells, which changes conformation and helps Gs, a [[heterotrimeric G protein]], exchange GDP to GTP. This trimeric G protein dissociates to [[Gs alpha subunit|Gs alpha]] and Gs beta/gamma subunits. Gs alpha stimulates [[adenylyl cyclase]], thus converting [[adenosine triphosphate]] into [[cyclic adenosine monophosphate]] (AMP). Cyclic AMP activates [[protein kinase A]]. Protein kinase A phosphorylates and partially activates [[phosphorylase kinase]]. Adrenaline also binds to α1 adrenergic receptors, causing an increase in [[inositol trisphosphate]], inducing calcium ions to enter the cytoplasm. Calcium ions bind to [[calmodulin]], which leads to further activation of phosphorylase kinase. Phosphorylase kinase phosphorylates [[glycogen phosphorylase]], which then breaks down [[glycogen]] leading to the production of glucose.{{cite book | vauthors = Berg JM, Tymoczko JL, Stryer L | title=Biochemistry |date=2002 |publisher=W.H. Freeman |location=New York |isbn=0-7167-3051-0 |edition=5th |url= https://www.ncbi.nlm.nih.gov/books/NBK22429/#:~:text=Glucagon%20and%20epinephrine%20trigger%20the%20breakdown%20of%20glycogen.&text=Epinephrine%20markedly%20stimulates%20glycogen%20breakdown,blood%2Dsugar%20level%20is%20low. | chapter=Epinephrine and Glucagon Signal the Need for Glycogen Breakdown}} [89] => [90] => Adrenaline also has significant effects on the cardiovascular system. It increases peripheral resistance via [[Alpha-1 adrenergic receptor|α1 receptor]]-dependent [[vasoconstriction]] and increases [[cardiac output]] by binding to β1 receptors. The goal of reducing peripheral circulation is to increase coronary and cerebral perfusion pressures and therefore increase oxygen exchange at the cellular level.{{cite web |title=Guideline 11.5: Medications in Adult Cardiac Arrest|url=http://resus.org.au/?wpfb_dl=55|format=PDF|work=Australian Resuscitation Council|date=December 2010|access-date=7 March 2015}}{{cite journal | vauthors = Chang YT, Huang WC, Cheng CC, Ke MW, Tsai JS, Hung YM, Huang NC, Huang MS, Wann SR | title = Effects of epinephrine on heart rate variability and cytokines in a rat sepsis model | journal = Bosnian Journal of Basic Medical Sciences | volume = 20 | issue = 1 | pages = 88–98 | date = February 2020 | pmid = 29984678 | pmc = 7029199 | doi = 10.17305/bjbms.2018.3565 }} While adrenaline does increase aortic, cerebral, and carotid circulation pressure, it lowers carotid blood flow and [[capnography|end-tidal CO2]] or ETCO2 levels. It appears that adrenaline improves microcirculation at the expense of the capillary beds where perfusion takes place.{{cite journal | vauthors = Burnett AM, Segal N, Salzman JG, McKnite MS, Frascone RJ | title = Potential negative effects of epinephrine on carotid blood flow and ETCO2 during active compression-decompression CPR utilizing an impedance threshold device | journal = Resuscitation | volume = 83 | issue = 8 | pages = 1021–1024 | date = August 2012 | pmid = 22445865 | doi = 10.1016/j.resuscitation.2012.03.018 }} [91] => [92] => ==Measurement in biological fluids== [93] => Adrenaline may be quantified in blood, plasma, or serum as a diagnostic aid, to monitor therapeutic administration, or to identify the causative agent in a potential poisoning victim. Endogenous plasma adrenaline concentrations in resting adults usually are less than 10 ng/L, but they may increase by 10-fold during exercise and by 50-fold or more during times of stress. [[Pheochromocytoma]] patients often have plasma adrenaline levels of 1000–10,000 ng/L. Parenteral administration of adrenaline to acute-care cardiac patients can produce plasma concentrations of 10,000 to 100,000 ng/L.{{cite journal | vauthors = Raymondos K, Panning B, Leuwer M, Brechelt G, Korte T, Niehaus M, Tebbenjohanns J, Piepenbrock S | title = Absorption and hemodynamic effects of airway administration of adrenaline in patients with severe cardiac disease | journal = Annals of Internal Medicine | volume = 132 | issue = 10 | pages = 800–803 | date = May 2000 | pmid = 10819703 | doi = 10.7326/0003-4819-132-10-200005160-00007 | s2cid = 12713291 }}{{cite book | vauthors = Baselt R |title=Disposition of Toxic Drugs and Chemicals in Man |edition=8th |publisher=Biomedical Publications |location=Foster City, CA |year=2008 |pages=545–547 |isbn=978-0-9626523-7-0}} [94] => [95] => ==Biosynthesis== [96] => [[File:Catecholamines biosynthesis.svg|thumb|right|upright=1.15|The biosynthesis of adrenaline involves a series of enzymatic reactions.]] [97] => [98] => In chemical terms, adrenaline is one of a group of [[monoamine]]s called the [[catecholamine]]s. Adrenaline is synthesized in the [[Medullary chromaffin cell|chromaffin cell]]s of the [[adrenal gland]]'s [[adrenal medulla]] and a small number of neurons in the [[medulla oblongata]] in the brain through a [[metabolic pathway]] that converts the [[amino acid]]s [[phenylalanine]] and [[tyrosine]] into a series of metabolic intermediates and, ultimately, adrenaline.{{cite book |vauthors=von Bohlen und Haibach O, Dermietzel R |title=Neurotransmitters and Neuromodulators: Handbook of Receptors and Biological Effects |url=https://books.google.com/books?id=AfmA_KJMjJAC&pg=PA125 |year=2006 |publisher=Wiley-VCH |isbn=978-3-527-31307-5 |page=125}} Tyrosine is first oxidized to [[L-DOPA|L-DOPA]] by [[tyrosine hydroxylase]]; this is the rate-limiting step. Then it is subsequently decarboxylated to give [[dopamine]] by DOPA decarboxylase ([[aromatic L-amino acid decarboxylase|aromatic L-amino acid decarboxylase]]). Dopamine is then converted to [[noradrenaline]] by [[dopamine beta-hydroxylase]], which utilizes ascorbic acid ([[vitamin C]]) and copper. The final step in adrenaline biosynthesis is the [[methylation]] of the [[primary amine]] of noradrenaline. This reaction is catalyzed by the enzyme [[phenylethanolamine N-methyltransferase|phenylethanolamine ''N''-methyltransferase]] (PNMT), which utilizes [[S-adenosyl methionine|''S''-adenosyl methionine]] (SAMe) as the [[methyl]] donor.{{cite journal |vauthors=Kirshner N, Goodall M |title=The formation of adrenaline from noradrenaline |journal=Biochimica et Biophysica Acta |volume=24 |issue=3 |pages=658–659 |date=June 1957 |pmid=13436503 |doi=10.1016/0006-3002(57)90271-8}} While PNMT is found primarily in the [[cytosol]] of the [[endocrine]] cells of the [[adrenal medulla]] (also known as [[chromaffin cell]]s), it has been detected at low levels in both the [[heart]] and [[brain]].{{cite journal |vauthors=Axelrod J |title=Purification and properties of phenylethanolamine-''N''-methyl transferase |journal=The Journal of Biological Chemistry |volume=237 |issue=5 |pages=1657–1660 |date=May 1962 |pmid=13863458 |doi=10.1016/S0021-9258(19)83758-4 |doi-access=free}} [99] => {{Catecholamine and trace amine biosynthesis|align=left|caption=Epinephrine is produced in a small group of neurons in the human brain (specifically, in the [[medulla oblongata]]) via the metabolic pathway shown above.}}{{clear left}} [100] => [101] => ===Regulation=== [102] => The major physiologic triggers of adrenaline release center upon [[stress (medicine)|stresses]], such as physical threat, excitement, noise, bright lights, and high or low ambient temperature. All of these stimuli are processed in the [[central nervous system]].{{cite book |vauthors=Nelson L, Cox M |year=2004 |title=Lehninger Principles of Biochemistry |edition=4th |location=New York |publisher=Freeman |page=[https://archive.org/details/lehningerprincip00lehn_0/page/908 908] |isbn=0-7167-4339-6 |url-access=registration |url=https://archive.org/details/lehningerprincip00lehn_0}} [103] => [104] => [[Adrenocorticotropic hormone]] (ACTH) and the [[sympathetic nervous system]] stimulate the synthesis of adrenaline precursors by enhancing the activity of [[tyrosine hydroxylase]] and [[Dopamine beta-hydroxylase|dopamine β-hydroxylase]], two key enzymes involved in catecholamine synthesis.{{Citation needed|date=April 2009}} ACTH also stimulates the [[adrenal cortex]] to release [[cortisol]], which increases the expression of PNMT in chromaffin cells, enhancing adrenaline synthesis. This is most often done in response to stress.{{Citation needed|date=April 2009}} The sympathetic nervous system, acting via [[splanchnic nerve]]s to the adrenal medulla, stimulates the release of adrenaline. [[Acetylcholine]] released by preganglionic sympathetic fibers of these nerves acts on [[nicotinic acetylcholine receptor]]s, causing cell depolarization and an influx of [[calcium]] through [[voltage-gated calcium channel]]s. Calcium triggers the [[exocytosis]] of chromaffin granules and, thus, the release of adrenaline (and noradrenaline) into the bloodstream.{{citation needed|date=January 2019}} For noradrenaline to be acted upon by PNMT in the cytosol, it must first be shipped out of [[chromaffin granule|granules]] of the chromaffin cells. This may occur via the catecholamine-H+ exchanger [[VMAT1]]. VMAT1 is also responsible for transporting newly synthesized adrenaline from the cytosol back into chromaffin granules in preparation for release.{{cite web|title=SLC18 family of vesicular amine transporters |url=http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=193 |access-date=21 August 2015|website=Guide to Pharmacology|publisher=IUPHAR/BPS}} [105] => [106] => Unlike many other hormones, adrenaline (as with other catecholamines) does not exert [[negative feedback]] to [[down-regulate]] its own synthesis. Abnormal adrenaline levels can occur in various conditions, such as surreptitious adrenaline administration, [[pheochromocytoma]], and other tumors of the [[sympathetic ganglia]]. [107] => [108] => Its action is terminated with reuptake into nerve terminal endings, some minute dilution, and metabolism by [[monoamine oxidase]]{{cite journal |vauthors=Oanca G, Stare J, Mavri J |title=How fast monoamine oxidases decompose adrenaline? Kinetics of isoenzymes A and B evaluated by empirical valence bond simulation |journal=Proteins |volume=85 |issue=12 |pages=2170–2178 |date=December 2017 |pmid=28836294 |doi=10.1002/prot.25374 |s2cid=5491090}} and [[catechol-O-methyl transferase|catechol-''O''-methyl transferase]] into [[3,4-Dihydroxymandelic acid]] and [[Metanephrine]]. [109] => [110] => == History == [111] => {{Main|History of catecholamine research}} [112] => Extracts of the [[adrenal gland]] were first obtained by Polish physiologist [[Napoleon Cybulski]] in 1895.{{cite book| vauthors=Szablewski L |title=Glucose Homeostasis and Insulin Resistance|date=2011 |publisher=Bentham Science Publishers|isbn=9781608051892|page=68|url=https://books.google.com/books?id=Dw3vfMM3wiIC&pg=PA68|language=en}} These extracts, which he called ''nadnerczyna'' ("adrenalin"), contained adrenaline and other catecholamines.{{cite journal | vauthors = Skalski JH, Kuch J | title = Polish thread in the history of circulatory physiology | journal = Journal of Physiology and Pharmacology | volume = 57 | issue = Suppl 1 | pages = 5–41 | date = April 2006 | pmid = 16766800 | url = http://www.jpp.krakow.pl/journal/archive/04_06_s1/articles/01_article.html }} American ophthalmologist [[William Bates (physician)|William H. Bates]] discovered adrenaline's usage for eye surgeries prior to 20 April 1896.{{cite journal | vauthors = Bates WH | title = The Use of Extract of Suprarenal Capsule in the Eye | journal = New York Medical Journal |date=16 May 1896 |pages=647–650 | quote = Read before the Section in Ophthalmology of the New York Academy of Medicine, 20 April 1896 |url=http://www.central-fixation.com/bates-medical-articles/use-of-extract-of-suprarenal-capsule.php |access-date=7 March 2015}} In 1897, [[John Jacob Abel]] (1857–1938), the father of modern pharmacology, found a natural substance produced by the adrenal glands that he named epinephrine. The first hormone to be identified, it remains a crucial, first-line treatment for cardiac arrests, severe allergic reactions, and other conditions. In 1901, Jokichi Takamine successfully isolated and purified the hormone from the adrenal glands of sheep and oxen.{{cite journal | vauthors = Takamine J |title=The isolation of the active principle of the suprarenal gland | journal = The Journal of Physiology |publisher=Cambridge University Press |location=Great Britain |year=1901|pages=xxix–xxx |url=https://books.google.com/books?id=xVEq06Ym6qcC&pg=RA1-PR29 }} Adrenaline was first synthesized in the laboratory by [[Friedrich Stolz]] and [[Henry Drysdale Dakin]], independently, in 1904.{{cite journal | vauthors = Bennett MR | title = One hundred years of adrenaline: the discovery of autoreceptors | journal = Clinical Autonomic Research | volume = 9 | issue = 3 | pages = 145–159 | date = June 1999 | pmid = 10454061 | doi = 10.1007/BF02281628 | s2cid = 20999106 }} [113] => [114] => Although secretin is mentioned as the first hormone, adrenaline is the first hormone since the discovery of the activity of adrenal extract on blood pressure was observed in 1895 before that of [[secretin]] in 1902. In 1895, George Oliver (1841–1915), a general practitioner in North Yorkshire, and Edward Albert Schäfer (1850–1935), a physiologist at University College of London published a paper about the active component of [[adrenal gland]] extract causing the increase in blood pressure and heart rate was from the medulla, but not the cortex of the adrenal gland.{{cite journal | vauthors = Ball CM, Featherstone PJ | title = The early history of adrenaline | journal = Anaesthesia and Intensive Care | volume = 45 | issue = 3 | pages = 279–281 | date = May 2017 | pmid = 28486885 | doi = 10.1177/0310057X1704500301 | doi-access = free }} In 1897, [[John Jacob Abel]] (1857–1938) of [[Johns Hopkins University]], the first chairman of the first US department of pharmacology, found a compound called epinephrine with the molecular formula of C17H15NO4. Abel claimed his principle from adrenal gland extract was active. [115] => [116] => In 1900, Jōkichi Takamine (1854–1922), a Japanese chemist, worked with his assistant, {{ill|Keizo Uenaka|ja|上中啓三}} (1876–1960), to purify a 2000 times more active principle than epinephrine from the adrenal gland, named adrenaline with the molecular formula C10H15NO3. Additionally, in 1900 Thomas Aldrich of Parke-Davis Scientific Laboratory also purified adrenaline independently. Takamine and Parke-Davis later in 1901 both got the patent for adrenaline. The fight for terminology between adrenaline and epinephrine was not ended until the first adrenaline structural discovery by Hermann Pauly (1870-1950) in 1903 and the first adrenaline synthesis by [[Friedrich Stolz]] (1860–1936), a German chemist in 1904. They both believed that Takamine's compound was the active principle while Abel's compound was the inactive one.{{citation needed|date=January 2022}} Stolz synthesized adrenaline from its ketone form (adrenalone).{{cite journal | vauthors = Arthur G | title = Epinephrine: a short history | journal = The Lancet. Respiratory Medicine | volume = 3 | issue = 5 | pages = 350–351 | date = May 2015 | pmid = 25969360 | doi = 10.1016/S2213-2600(15)00087-9 | doi-access = free }} [117] => [118] => ==Society and culture== [119] => ===Adrenaline junkie=== [120] => {{See also|Novelty seeking}} [121] => An ''adrenaline junkie'' is someone who engages in sensation-seeking behavior through "the pursuit of novel and intense experiences without regard for physical, social, legal or financial risk".{{cite book |url=https://books.google.com/books?id=RGcQAQAAIAAJ|doi=10.1016/0191-8869(93)90173-Z|vauthors=Zuckerman M|date=2007|title=Sensation seeking and risky behavior |publisher=American Psychological Association|location=Washington, DC|isbn=9781591477389}} Such activities include extreme and risky sports, substance abuse, unsafe sex, and crime. The term relates to the increase in circulating levels of adrenaline during physiological [[stress (biology)|stress]].{{cite book|vauthors=Jänig W|date=6 July 2006|title=The integrative action of the autonomic nervous system: neurobiology of homeostasis|publisher=Cambridge University Press |url=https://books.google.com/books?id=5jOZmAEACAAJ|location=England|isbn=9780521845182|pages=143–146}} Such an increase in the circulating concentration of adrenaline is secondary to the activation of the sympathetic nerves innervating the adrenal medulla, as it is rapid and not present in animals where the adrenal gland has been removed.{{cite book| vauthors=Deane WH, Rubin BL |title=The Adrenocortical Hormones Their Origin – Chemistry Physiology and Pharmacology|date=1964|publisher=Springer Berlin Heidelberg|location=Berlin, Heidelberg |isbn=9783662131329|pages=105|chapter=Absence of adrenal meduallary secretions}} Although such stress triggers adrenaline release, it also activates many other responses within the central nervous system [[reward system]], which drives behavioral responses; while the circulating adrenaline concentration is present, it may not drive behavior. Nevertheless, adrenaline infusion alone does increase alertness{{cite journal |vauthors=Frankenhaeuser M, Jarpe G, Matell G |title=Effects of intravenous infusions of adrenaline and noradrenaline on certain psychological and physiological functions |journal=Acta Physiologica Scandinavica |volume=51 |issue=2–3 |pages=175–186 |date=February 1961 |pmid=13701421 |doi=10.1111/j.1748-1716.1961.tb02126.x}} and has roles in the brain, including the augmentation of memory consolidation. [122] => [123] => ===Strength=== [124] => {{main|Hysterical strength}} [125] => Adrenaline has been implicated in feats of great strength, often occurring in times of crisis. For example, there are stories of a parent lifting part of a car when their child is trapped underneath.{{cite news|vauthors=Wise J|title=When Fear Makes Us Superhuman|url=http://www.scientificamerican.com/article/extreme-fear-superhuman/|access-date=25 August 2015|publisher=Scientific American|date=28 December 2009}}{{cite book| vauthors = Wise J |title=Extreme Fear: The Science of Your Mind in Danger|url=https://books.google.com/books?id=og9ykAB7wEsC|date=8 December 2009|publisher=[[Palgrave Macmillan]]|location=New York|isbn=9780230101807|edition=1st }} [126] => [127] => ==See also== [128] => *[[Noradrenaline]] [129] => *[[Catecholamines]] [130] => *[[Adrenal gland]] [131] => [132] => ==References== [133] => {{Reflist}} [134] => [135] => ==External links== [136] => {{Wiktionary|adrenaline junkie}} [137] => *{{Commonscatinline|Epinephrine}} [138] => *{{cite web|url=http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Epinephrine|title=U.S. National Library of Medicine: Drug Information Portal – Epinephrine|url-status=dead|archive-date=14 December 2019|archive-url=https://web.archive.org/web/20191214212813/https://druginfo.nlm.nih.gov/drugportal/name/Epinephrine}} [139] => [140] => {{Hormones}} [141] => {{Neurotransmitters}} [142] => [143] => {{Adrenergic receptor modulators}} [144] => {{Phenethylamines}} [145] => {{Emergency medicine}} [146] => {{Authority control}} [147] => [148] => [[Category:Adrenaline| ]] [149] => [[Category:Anxiety]] [150] => [[Category:Articles containing video clips]] [151] => [[Category:Alpha-adrenergic agonists]] [152] => [[Category:Beta-adrenergic agonists]] [153] => [[Category:Bronchodilators]] [154] => [[Category:Carbonic anhydrase activators]] [155] => [[Category:Cardiac stimulants]] [156] => [[Category:Catecholamines]] [157] => [[Category:Hormones of the hypothalamus-pituitary-adrenal axis]] [158] => [[Category:Hormones of the suprarenal medulla]] [159] => [[Category:Neurotransmitters]] [160] => [[Category:Norepinephrine releasing agents]] [161] => [[Category:Stress (biology)]] [162] => [[Category:Sympathomimetic amines]] [163] => [[Category:Chemical substances for emergency medicine]] [164] => [[Category:Phenylethanolamines]] [165] => [[Category:Human metabolites]] [] => )
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Adrenaline

Adrenaline is a hormone and neurotransmitter produced by the adrenal glands, as well as certain neurons within the central nervous system. It plays a crucial role in the body's response to stress and danger, commonly known as the "fight-or-flight" response.

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It plays a crucial role in the body's response to stress and danger, commonly known as the "fight-or-flight" response. When released in response to a perceived threat, adrenaline enhances physical and mental abilities, increasing heart rate, blood pressure, and energy levels. It also dilates air passages, improves muscle strength, and increases the blood flow to the brain. In addition to its role in the stress response, adrenaline is involved in various physiological processes, including regulating blood sugar levels, metabolism, and immune system function. It acts on various receptors throughout the body, affecting different organs and systems. Adrenaline is also used as a medication to treat conditions like anaphylaxis, cardiac arrest, and asthma. The production and release of adrenaline are regulated by the hypothalamus, which signals the adrenal glands to release the hormone when stress is detected. The release can be triggered by various stimuli, such as physical or emotional stress, exercise, pain, or fear. Once released, adrenaline binds to specific receptors on target cells, initiating various physiological responses. Although adrenaline is essential for survival and can bring about a temporary boost in performance, chronic exposure to stress and high levels of adrenaline can have detrimental effects on health. Prolonged stress can lead to various physical and mental health problems, such as cardiovascular disease, anxiety, and weakened immune function. Overall, adrenaline is a vital hormone that plays a central role in the body's response to stress and danger. Its effects on the body and mind help prepare individuals to handle threatening situations and perform at their best. However, maintaining a balance and effectively managing stress levels are crucial for overall health and well-being.

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