Raymond P. Ahlquist
|Raymond Perry Ahlquist|
Courtesy of the National Library of Medicine.
26 July 1914|
|Died||15 April 1983
|Institutions||Medical College of Georgia|
|Alma mater||University of Washington|
|Known for||discovery of adrenoceptor subtypes|
|Notable awards||Lasker award (1976)|
Raymond Perry Ahlquist (July 26, 1914, Missoula, Montana – April 15, 1983, Augusta, Georgia) 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 ground work for new drugs including the widely prescribed beta blockers.
Ahlquist's parents both 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. In Seattle, he met his wife Dorothy Duff Ahlquist. He then 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.
In South Dakota, Ahlquist searched for a substitute for the Chinese plant-derived and scarce ephedrine. 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 that time who could not explain how a single agent could have both excitatory and inhibitory effects.
In his famous work 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 are two different receptors for agonists. 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: "At the moment can be said about the nature of the adrenoceptors and the difference between the α-and β-types do not say much, but should the subdivision concept be useful in exploring the various effects of adrenaline and other sympathomimetic agents and the effects of the sympathetic nervous system."
The publication was initially dismissed but went on to have a major impact on pharmacology. 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. 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 drug therapy, his discovery laid the foundation for the development of beta blockers to treat heart disease and also reduce high blood pressure.
Ahlquist's other scientific work also includes the pharmacology of the sympathetic nervous system. His research contribute to the discovery of tolazoline, a substance with a completely different chemical structure than the adrenaline and noradrenaline and in 1958, dichloroisoprenaline the first clinically useful beta-blocker. It was discovered with his help that the peristalsis is enhanced by α-adrenoceptors and conversely inhibited by β-adrenoceptors.
In his most recent essay in 1980, he looked back to the 1948 publication. The impact of the 1948 publication is evident by the number of times it has been cited (2766 times as of 2011).
- Sutherland JHR, Carrier GO, Greenbaum LM (1983). "Dr. Raymond P. Ahlquist". The Pharmacologist 25 (1): 73.
- Wenger NK, Greenbaum LM (February 1984). "From adrenoceptor mechanisms to clinical therapeutics: Raymond Ahlquist, Ph.D., 1914-1983". J. Am. Coll. Cardiol. 3 (2 Pt 1): 419–21. PMID 6141195.
- Little RC (August 1988). "Raymond P. Ahlquist (1914-1983)". Clinical Cardiology 11 (8): 583–584. doi:10.1002/clc.4960110815.
- Ahlquist RP (June 1948). "A study of the adrenotropic receptors". Am. J. Physiol. 153 (3): 586–600. PMID 18882199.
- Rubin RP (December 2007). "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". Pharmacol. Rev. 59 (4): 289–359. doi:10.1124/pr.107.70102. PMID 18160700.
- Starke K (November 2011). "[The history of the α-adrenoceptor agonists]". Pharm Unserer Zeit (in German) 40 (6): 456–61. doi:10.1002/pauz.201100439. PMID 22028128.
- Ahlquist RP, Huggins RA, Woodbury RA (March 1947). "The pharmacology of benzyl-imidazoline (Priscol)". J. Pharmacol. Exp. Ther. 89 (3): 271–88. PMID 20290430.
- Ahlquist RP, Levy B (October 1959). "Andrenergic receptive mechanism of canine ileum". J. Pharmacol. Exp. Ther. 127: 146–9. PMID 13792127.
- Ahlquist RP (November 1980). "Historical perspective. Classification of adrenoreceptors". J Auton Pharmacol 1 (1): 101–6. PMID 6122687.
- "Oscar B. Hunter Award". American Society for Clinical Therapeutics and Pharmacology. Retrieved 2012-05-24.
- "The Lasker Foundation - 1976 Clinical Medical Research Award". The Lasker Foundation. Retrieved 2012-05-24.