Editing Acetylcholine (section)

==History==
In 1867, [[Adolf von Baeyer]] resolved the structures of [[choline]] and acetylcholine and synthesized them both, referring to the latter as ''acetylneurin'' in the study.<ref name=b>{{Cite journal|vauthors=Baeyer A|date=1867|title=I. Üeber das neurin|journal=Justus Liebigs Ann Chem|language=de|volume=142|issue=3|pages=322–326|doi=10.1002/jlac.18671420311|url=https://zenodo.org/record/2483316}}</ref><ref name=c>{{cite journal|vauthors=Kawashima K, Fujii T, Moriwaki Y, Misawa H, Horiguchi K|title=Non-neuronal cholinergic system in regulation of immune function with a focus on α7 nAChRs|journal=International Immunopharmacology|volume=29|issue=1|pages=127–34|date=2015|pmid=25907239|doi=10.1016/j.intimp.2015.04.015|doi-access=free}}</ref> Choline is a precursor for acetylcholine. Acetylcholine was first noted to be biologically active in 1906, when [[Reid Hunt]] (1870–1948) and René de M. Taveau found that it decreased [[blood pressure]] in exceptionally tiny doses.<ref>{{Cite journal|vauthors=Hunt R, Taveau M|date=1906|title=On the physiological action of certain choline derivatives and new methods for detecting choline|journal=BMJ|volume=2|pages=1788–1791}}</ref><ref name=c/><ref>{{cite journal|vauthors=Dorkins HR|title=Suxamethonium-the development of a modern drug from 1906 to the present day|journal=Medical History|volume=26|issue=2|pages=145–68|date=April 1982|pmid=7047939|pmc=1139149|doi=10.1017/s0025727300041132 }}</ref> This was after [[Frederick Walker Mott]] and [[William Dobinson Halliburton]] noted in 1899 that choline injections decreased the blood pressure of animals.<ref>{{Cite journal|vauthors=Mott FW, Halliburton WD|date=1899|title=VII. The physiological action of choline and neurine|journal=Philosophical Transactions of the Royal Society of London. Series B, Containing Papers of a Biological Character|volume=191|issue=2001|pages=211–267|doi=10.1098/rstb.1899.0007|pmid=20758460|pmc=2463419|doi-access=free}}</ref><ref name=c/>

In 1914, Arthur J. Ewins was the first to extract acetylcholine from nature. He identified it as the blood pressure-decreasing contaminant from some ''[[Claviceps purpurea]]'' [[ergot]] extracts, by the request of [[Henry Hallett Dale]].<ref name=c/> Later in 1914, Dale outlined the effects of acetylcholine at various types of peripheral synapses and also noted that it lowered the blood pressure of cats via [[subcutaneous injection]]s even at doses of one [[nanogram]].<ref name=a>{{Cite journal|vauthors=Dale HH|date=1914|title=The action of certain esters and ethers of choline, and their relation to muscarine|url=http://jpet.aspetjournals.org/content/6/2/147|journal=J Pharmacol Exp Ther|volume=6|issue=2|pages=147–190|doi=10.1016/S0022-3565(25)08268-0 }}</ref><ref name=c/>

The concept of [[neurotransmitter]]s was unknown until 1921, when [[Otto Loewi]] noted that the [[vagus nerve]] secreted a substance that inhibited the [[heart muscle]] whilst working as a professor in the [[University of Graz]]. He named it ''[[vagusstoff]]'' ("vagus substance"), noted it to be a [[structural analog]] of choline and suspected it to be acetylcholine.<ref>{{Cite journal|vauthors=Loewi O|date=1922|title=Über humorale übertragbarkeit der herznervenwirkung|journal=Pflug Arch Ges Phys|language=de|volume=193|issue=1|pages=201–213|doi=10.1007/BF02331588|s2cid=34861770}}</ref><ref name="his"/> In 1926, Loewi and E. Navratil deduced that the compound is probably acetylcholine, as vagusstoff and synthetic acetylcholine lost their activity in a similar manner when in contact with tissue [[lysate]]s that contained acetylcholine-degrading enzymes (now known to be [[cholinesterase]]s).<ref>{{Cite journal|vauthors=Loewi O, Navratil E|date=1926|title=Über humorale übertragbarkeit der herznervenwirkung|journal=Pflug Arch Ges Phys|language=de|volume=214|issue=1|pages=678–688|doi=10.1007/BF01741946|s2cid=43748121}}</ref><ref name="d">{{cite journal|vauthors=Zimmer HG|title=Otto Loewi and the chemical transmission of vagus stimulation in the heart|journal=Clinical Cardiology|volume=29|issue=3|pages=135–6|date=March 2006|pmid=16596840|pmc=6654523|doi=10.1002/clc.4960290313 }}</ref> This conclusion was accepted widely. Later studies confirmed the function of acetylcholine as a [[neurotransmitter]].<ref name="his">{{cite journal|vauthors=Zeisel SH|title=A brief history of choline|journal=Annals of Nutrition & Metabolism|volume=61|issue=3|pages=254–8|date=2012|pmid=23183298|pmc=4422379|doi=10.1159/000343120}}</ref>

In 1936, H. H. Dale and O. Loewi shared the [[Nobel Prize in Physiology or Medicine]] for their studies of acetylcholine and nerve impulses.<ref name=c/>