Editing Adrenergic receptor (section)

==History==
{{Main|History of catecholamine research}}

{{multiple image
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| image1 = Adrenalin - Adrenaline.svg
| caption1 = [[Epinephrine]]
| image2 = Noradrenalin - Noradrenaline.svg
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| caption2 = [[Norepinephrine]]
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By the turn of the 19th century, it was agreed that the stimulation of sympathetic nerves could cause different effects on body tissues, depending on the conditions of stimulation (such as the presence or absence of some toxin). Over the first half of the 20th century, two main proposals were made to explain this phenomenon:

# There were (at least) two different types of neurotransmitters released from sympathetic nerve terminals, or
# There were (at least) two different types of detector mechanisms for a single neurotransmitter.

The first hypothesis was championed by [[Walter Bradford Cannon]] and [[Arturo Rosenblueth]],<ref>{{cite journal | vauthors = Cannon WB, Rosenbluth A | date= 31 May 1933| title = Studies On Conditions Of Activity In Endocrine Organs XXVI: Sympathin E and Sympathin I | journal = American Journal of Physiology | volume= 104 | issue = 3 | pages = 557–574 | doi= 10.1152/ajplegacy.1933.104.3.557}}</ref> who interpreted many experiments to then propose that there were two neurotransmitter substances, which they called sympathin E (for 'excitation') and sympathin I (for 'inhibition').

The second hypothesis found support from 1906 to 1913, when [[Henry Hallett Dale]] explored the effects of adrenaline (which he called adrenine at the time), injected into animals, on blood pressure.  Usually, adrenaline would increase the blood pressure of these animals. Although, if the animal had been exposed to [[ergot]]oxine, the blood pressure decreased.<ref>{{cite journal | vauthors = Dale HH | title = On some physiological actions of ergot | journal = The Journal of Physiology | volume = 34 | issue = 3 | pages = 163–206 | date = May 1906 | pmid = 16992821 | doi =  10.1113/jphysiol.1906.sp001148 | pmc=1465771}}</ref><ref>{{cite journal | vauthors = Dale HH | title = On the action of ergotoxine; with special reference to the existence of sympathetic vasodilators | journal = The Journal of Physiology | volume = 46 | issue = 3 | pages = 291–300 | date = Jun 1913 | pmid = 16993202 | doi = 10.1113/jphysiol.1913.sp001592 | pmc=1420444}}</ref> He proposed that the ergotoxine caused "selective paralysis of motor myoneural junctions" (i.e. those tending to increase the blood pressure) hence revealing that under normal conditions that there was a "mixed response", including a mechanism that would relax smooth muscle and cause a fall in blood pressure. This "mixed response", with the same compound causing either contraction or relaxation, was conceived of as the response of different types of junctions to the same compound.

This line of experiments were developed by several groups, including DT Marsh and colleagues,<ref>{{cite journal | vauthors = Marsh DT, Pelletier MH, Rose CA | title = The comparative pharmacology of the N-alkyl-arterenols | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 92 | issue = 2 | pages = 108–20 | date = Feb 1948 | pmid = 18903395 }}</ref> who in February 1948 showed that a series of compounds structurally related to adrenaline could also show either contracting or relaxing effects, depending on whether or not other toxins were present. This again supported the argument that the muscles had two different mechanisms by which they could respond to the same compound. In June of that year, [[Raymond Ahlquist]], Professor of Pharmacology at Medical College of Georgia, published a paper concerning adrenergic nervous transmission.<ref>{{cite journal | vauthors = Ahlquist RP | s2cid = 1518772 | title = A study of the adrenotropic receptors | journal = The American Journal of Physiology | volume = 153 | issue = 3 | pages = 586–600 | date = Jun 1948 | pmid = 18882199 | doi =  10.1152/ajplegacy.1948.153.3.586}}</ref> In it, he explicitly named the different responses as due to what he called α receptors and β receptors, and that the only sympathetic transmitter was adrenaline. While the latter conclusion was subsequently shown to be incorrect (it is now known to be noradrenaline), his receptor nomenclature and concept of ''two different types of detector mechanisms for a single neurotransmitter'', remains.  In 1954, he was able to incorporate his findings in a textbook, ''Drill's Pharmacology in Medicine'',<ref>{{cite book|last=Drill|first=Victor Alexander|name-list-style=vanc|date=1954|title=Pharmacology in medicine: a collaborative textbook|url=https://archive.org/details/pharmacologyinme00dril|url-access=registration|location=New York|publisher=McGraw-Hill}}</ref> and thereby promulgate the  role played by α and β receptor sites in the adrenaline/noradrenaline cellular mechanism. These concepts would revolutionise advances in pharmacotherapeutic research, allowing the selective design of specific molecules to target medical ailments rather than rely upon traditional research into the efficacy of pre-existing herbal medicines.