{{Short description|American pharmacist and pharmacologist (1914–1983)}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox scientist |name = Raymond Perry Ahlquist | image = Raymond P Ahlquist.jpg | caption = Courtesy of the National Library of Medicine. | birth_date ={{birth date|1914|7|26|df=yes}} | birth_place = Missoula, Montana, United States | death_date = {{death date and age|1983|4|15|1914|7|26|df=yes}} | death_place = Augusta, Georgia | death_cause = | residence = | field = Pharmacology | work_institution = Medical College of Georgia | alma_mater = University of Washington | known_for = Discovery of adrenoceptor subtypes | prizes =Lasker award (1976) }}
'''Raymond Perry Ahlquist''' (July 26, 1914 – April 15, 1983) was an American pharmacist and pharmacologist. He published seminal work in 1948 that divided adrenoceptors into α- and β-adrenoceptor subtypes. This discovery explained the activity of several existing drugs and also laid the groundwork for new drugs including the widely prescribed beta blockers.<ref>{{cite journal | vauthors = Sutherland JH, Carrier GO, Greenbaum LM | title = Dr. Raymond P. Ahlquist | journal = The Pharmacologist | volume = 25 | issue = 1 | pages = 73 | year = 1983 }}</ref><ref name="Wenger_1984">{{cite journal | vauthors = Wenger NK, Greenbaum LM | title = From adrenoceptor mechanisms to clinical therapeutics: Raymond Ahlquist, Ph.D., 1914-1983 | journal = Journal of the American College of Cardiology | volume = 3 | issue = 2 Pt 1 | pages = 419–421 | date = February 1984 | pmid = 6141195 | doi = 10.1016/s0735-1097(84)80029-7 | doi-access = free }}</ref>
==Early life and education== Ahlquist was born on July 26, 1914, in Missoula, Montana. Both of his parents came from Sweden. His father was an auditor at the railway company Northern Pacific Railway. In 1940, Ahlquist graduated with a Ph.D. degree in pharmacology from the University of Washington in Seattle, the first person to be awarded such a degree from that institution.
==Career and research== Ahlquist spent four years as a faculty member at South Dakota State University in Brookings. In 1944 he became assistant professor of pharmacology at the Medical College of Georgia in Augusta. In 1946 he was appointed associate professor in the same institution and from 1948 to 1963 he was the chair of pharmacology. In 1963 he was appointed associate dean for basic sciences and research coordinator for the medical college. Between 1970 and 1977 he was again chair of pharmacology and in 1977 he was appointed Charbonnier Professor of Pharmacology, a post he held until his death.<ref name="Little_1988">{{cite journal | vauthors = Little RC | title = Raymond P. Ahlquist (1914-1983) | journal = Clinical Cardiology | volume = 11 | issue = 8 | pages = 583–584 | date = August 1988 | doi = 10.1002/clc.4960110815 | s2cid = 74396544 }}</ref>
===Adrenoceptors=== While working on a project in western South Dakota, Ahlquist searched for a substitute for the Chinese plant-derived and scarce ephedrine.<ref>{{cite journal | vauthors = Ahlquist RP | title = Historical perspective. Classification of adrenoreceptors | journal = Journal of Autonomic Pharmacology | volume = 1 | issue = 1 | pages = 101–106 | date = November 1980 | pmid = 6122687 | doi = 10.1111/j.1474-8673.1980.tb00445.x }}</ref> It has similar activity to that of adrenaline and noradrenaline - a sympathomimetic, i.e. a substance that stimulates the sympathetic nervous system. The actions of the sympathomimetics confused pharmacologists and physiologists at the time as they could not explain how a single agent could have both excitatory and inhibitory effects.
In his famous work<ref name="Ahlquist_1948" /> Ahlquist chose six agonists, including epinephrine, norepinephrine, α-methyl noradrenaline and isoprenaline, and examined their effects on several organs, including blood vessels and the heart. He found that the six substances possessed different rank orders of potency that differed depending on the tissue. For example, the rank order of potency was "adrenaline > noradrenaline > α-methyl noradrenaline > isoprenaline" in promoting contraction of blood vessels, but the rank order was "isoprenaline > adrenaline > α-methyl noradrenaline > norepinephrine" in the heart. Ahlquist concluded that there were two different receptors. The receptors with the first rank order (that is, for example, for blood vessel contraction), he called α-adrenoceptors (alpha adrenotropic receptor) receptors, while the second rank order (for instance, for the promotion of cardiac activity), he called β-adrenoceptors.
Simultaneously both cautious and forward-looking, he wrote: "Although little can be said at the present time as to the fundamental nature of the adrenotropic receptor and the difference between the ''alpha'' and ''beta'' types, this concept should be useful when studying the various actions of epinephrine, the actions and interactions of the sympathomimetic agents, and the effects of sympathetic nerve stimulation."<ref name="Ahlquist_1948">{{cite journal | vauthors = Ahlquist RP | title = A study of the adrenotropic receptors | journal = The American Journal of Physiology | volume = 153 | issue = 3 | pages = 586–600 | date = June 1948 | pmid = 18882199 | doi = 10.1152/ajplegacy.1948.153.3.586 | s2cid = 1518772 }}</ref>
Ahlquist's classification was initially dismissed and took some time to be accepted,<ref>{{cite journal | vauthors = Bylund DB | title = Alpha- and beta-adrenergic receptors: Ahlquist's landmark hypothesis of a single mediator with two receptors | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 293 | issue = 6 | pages = E1479–E1481 | date = December 2007 | pmid = 17957033 | doi = 10.1152/ajpendo.00664.2007 }}</ref> but it went on to have a major impact on pharmacology.<ref name="Little_1988" /><ref name="Rubin_2007" /> The manuscript was first rejected by the ''Journal of Pharmacology and Experimental Therapeutics'', but was subsequently accepted for publication by the ''American Journal of Physiology''.<ref name="Little_1988" /><ref name="Rubin_2007" /> As for Ahlquist's inquiry into the nature of adrenoceptors, we now know that they are G protein-coupled receptors and humans possess a total of nine different adrenoceptors (α1A, α1B, α1D, α2A, α2B α2C, β1, β2, β3). In the field of therapeutics, his discovery laid the foundation for the development of beta blockers by Sir James Black<ref>{{cite journal | vauthors = Quirke V | title = Putting theory into practice: James Black, receptor theory and the development of the beta-blockers at ICI, 1958-1978 | journal = Medical History | volume = 50 | issue = 1 | pages = 69–92 | date = January 2006 | pmid = 16502872 | pmc = 1369014 | doi = 10.1017/s0025727300009455 }}</ref> to treat heart disease and reduce high blood pressure.<ref name="Rubin_2007">{{cite journal | vauthors = Rubin RP | title = A brief history of great discoveries in pharmacology: in celebration of the centennial anniversary of the founding of the American Society of Pharmacology and Experimental Therapeutics | journal = Pharmacological Reviews | volume = 59 | issue = 4 | pages = 289–359 | date = December 2007 | pmid = 18160700 | doi = 10.1124/pr.107.70102 | s2cid = 33152970 }}</ref><ref name="Starke_2011">{{cite journal | vauthors = Starke K | title = [The history of the α-adrenoceptor agonists] | journal = Pharmazie in unserer Zeit | volume = 40 | issue = 6 | pages = 456–461 | date = November 2011 | pmid = 22028128 | doi = 10.1002/pauz.201100439 | language = de }}</ref>
===Other work=== Ahlquist's other scientific work also included studies on the pharmacology of the sympathetic nervous system. His research contributed to the discovery of tolazoline, a non-selective α-adrenergic receptor antagonist with a completely different chemical structure from adrenaline and noradrenaline<ref name="Ahlquist_1947">{{cite journal | vauthors = Ahlquist RP, Huggins RA, Woodbury RA | title = The pharmacology of benzyl-imidazoline (Priscol) | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 89 | issue = 3 | pages = 271–288 | date = March 1947 | doi = 10.1016/S0022-3565(25)05856-2 | pmid = 20290430 }}</ref> and in 1958, dichloroisoprenaline, the first beta-blocker. He also contributed to the discovery that peristalsis is enhanced by α-adrenoceptors and inhibited by β-adrenoceptors.<ref name="Ahlquist_1959">{{cite journal | vauthors = Ahlquist RP, Levy B | title = Andrenergic receptive mechanism of canine ileum | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 127 | pages = 146–149 | date = October 1959 | issue = 2 | doi = 10.1016/S0022-3565(25)25671-3 | pmid = 13792127 }}</ref>
In his last published article in 1980, he looked back to the 1948 publication.<ref name="Ahlquist_1980">{{cite journal | vauthors = Ahlquist RP | title = Historical perspective. Classification of adrenoreceptors | journal = Journal of Autonomic Pharmacology | volume = 1 | issue = 1 | pages = 101–106 | date = November 1980 | pmid = 6122687 | doi = 10.1111/j.1474-8673.1980.tb00445.x }}</ref> The impact of the 1948 publication is evident by the number of times it has been cited (5,220 times as of 28-01-2025).<ref>{{Cite web | title = Articles citing: Ahlquist (1948) A study of the adrenotropic receptors | work = Google Scholar | url = https://scholar.google.com/scholar?hl=en&as_sdt=2005&sciodt=0,5&cites=13600575638503446025&scipsc=&as_ylo=1900&as_yhi=2024 | access-date = 2025-01-28 }}</ref>
==Awards== Ahlquist was awarded the Oscar B. Hunter Memorial Award in Therapeutics,<ref name="urlOscar B. Hunter Award">{{cite web | title = Oscar B. Hunter Award | url = http://www.ascpt.org/AboutUs/Awards/OscarBHunterAward/tabid/6745/Default.aspx | publisher = American Society for Clinical Therapeutics and Pharmacology | access-date = 2012-05-24 }}</ref> the Ciba Award for Hypertension Research and the Albert Lasker Award for Clinical Medical Research.<ref name="urlThe Lasker Foundation - 1976 Clinical Medical Research Award">{{cite web | title = The Lasker Foundation - 1976 Clinical Medical Research Award | url = http://www.laskerfoundation.org/awards/1976_c_description.htm | publisher = The Lasker Foundation | access-date = 2012-05-24 | archive-date = 2010-07-16 | archive-url = https://web.archive.org/web/20100716184614/http://www.laskerfoundation.org/awards/1976_c_description.htm | url-status = dead }}</ref>
==Personal==
Ahlquist met his wife Dorothy Duff Ahlquist in Seattle.
==Death==
Ahlquist died on April 15, 1983, in Augusta, Georgia
== References == {{Reflist}}
== External links == * [http://www.southalabama.edu/ishr/hn&v/hnv8_1.pdf Biography on southalabama.edu] {{Webarchive|url=https://web.archive.org/web/20160304195009/http://www.southalabama.edu/ishr/hn%26v/hnv8_1.pdf |date=2016-03-04 }}
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{{DEFAULTSORT:Ahlquist, Raymond P.}} Category:1914 births Category:1983 deaths Category:American people of Swedish descent Category:Recipients of the Lasker–DeBakey Clinical Medical Research Award Category:American pharmacologists Category:20th-century American chemists Category:South Dakota State University faculty Category:Augusta University faculty