Raymond P. Ahlquist
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Raymond Perry Ahlquist (July 26, 1914 – April 15, 1983) was an American
pharmacist A pharmacist, also known as a chemist (Commonwealth English) or a druggist (North American and, archaically, Commonwealth English), is a healthcare professional who prepares, controls and distributes medicines and provides advice and instructi ...
and
pharmacologist Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemic ...
. 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 A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalati ...
including the widely prescribed
beta blockers Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack ( secondary prevention). They are ...
.


Early life and education

Ahlquist was born on July, 26 1914 in Missoula,
Montana Montana () is a state in the Mountain West division of the Western United States. It is bordered by Idaho to the west, North Dakota and South Dakota to the east, Wyoming to the south, and the Canadian provinces of Alberta, British Columb ...
. Both of his parents came from
Sweden Sweden, formally the Kingdom of Sweden,The United Nations Group of Experts on Geographical Names states that the country's formal name is the Kingdom of SwedenUNGEGN World Geographical Names, Sweden./ref> is a Nordic countries, Nordic c ...
. His father was an auditor at the Railway Company
Northern Pacific Railway The Northern Pacific Railway was a transcontinental railroad that operated across the northern tier of the western United States, from Minnesota to the Pacific Northwest. It was approved by Congress in 1864 and given nearly of land grants, wh ...
. In 1940, Ahlquist graduated with a Ph.D. degree in
pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
from the
University of Washington The University of Washington (UW, simply Washington, or informally U-Dub) is a public research university in Seattle, Washington. Founded in 1861, Washington is one of the oldest universities on the West Coast; it was established in Seatt ...
in
Seattle Seattle ( ) is a seaport city on the West Coast of the United States. It is the seat of King County, Washington. With a 2020 population of 737,015, it is the largest city in both the state of Washington and the Pacific Northwest region o ...
, 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 South Dakota State University is a public land-grant research university in Brookings, South Dakota. Founded in 1881, it is the state's largest and most comprehensive university and the oldest continually-operating university in South Dakota. The ...
in Brookings. In 1944 he became
Assistant Professor Assistant Professor is an academic rank just below the rank of an associate professor used in universities or colleges, mainly in the United States and Canada. Overview This position is generally taken after earning a doctoral degree A docto ...
of
Pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
at the
Medical College of Georgia The Medical College of Georgia (often referred to as MCG) is the flagship medical school of the University System of Georgia, the state's only public medical school, and one of the top 10 largest medical schools in the United States. Established ...
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.


Adrenoceptor

In South Dakota, Ahlquist searched for a substitute for the Chinese plant-derived and scarce
ephedrine Ephedrine is a central nervous system (CNS) stimulant that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in ...
. It has similar activity to that of
adrenaline Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands an ...
and
noradrenaline Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
- a
sympathomimetic Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in hea ...
, i.e. a substance that stimulates the
sympathetic nervous system The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of t ...
. 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 Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...
, 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 Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
. The
manuscript A manuscript (abbreviated MS for singular and MSS for plural) was, traditionally, any document written by hand – or, once practical typewriters became available, typewritten – as opposed to mechanically printed or reproduced i ...
was first rejected by the ''
Journal of Pharmacology and Experimental Therapeutics The ''Journal of Pharmacology and Experimental Therapeutics'' (a.k.a. JPET) is a peer-reviewed scientific journal covering pharmacology. It has been published since 1909 by the American Society for Pharmacology and Experimental Therapeutics (ASPET) ...
'', but was subsequently accepted for publication by the ''
American Journal of Physiology The ''American Journal of Physiology'' is a peer-reviewed scientific journal on physiology published by the American Physiological Society. Vols. for 1898–1941 and 1948-56 include the Society's proceedings, including abstracts of papers present ...
''. As for Ahlquist's inquiry into the nature of adrenoceptors, we now know that they are
G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
s 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 blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack ( secondary prevention). They are ...
s to treat heart disease and also reduce high
blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure ...
.


Other work

Ahlquist's other scientific work also includes the
pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
of the sympathetic
nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes ...
. His research contribute to the discovery of
tolazoline Tolazoline is a non-selective competitive α-adrenergic receptor antagonist. It is a vasodilator that is used to treat spasms of peripheral blood vessels (as in acrocyanosis). It has also been used (in conjunction with sodium nitroprusside) ...
, a substance with a completely different
chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of ...
than the adrenaline and noradrenaline and in 1958,
dichloroisoprenaline Dichloroisoprenaline (DCI), also known as dichloroisoproterenol, was the first beta blocker ever to be developed. It is non-selective for the β1-adrenergic and β2-adrenergic receptors. DCI has low potency and acts as a partial agonist/antagoni ...
the first clinically useful beta-blocker. It was discovered with his help that the
peristalsis Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, whi ...
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).


Awards

Ahlquist was awarded the Oscar B. Hunter Memorial Award in Therapeutics, the Ciba Award for Hypertension Research and the
Albert Lasker Award The Lasker Awards have been awarded annually since 1945 to living persons who have made major contributions to medical science or who have performed public service on behalf of medicine. They are administered by the Lasker Foundation, which was f ...
for Clinical Medical Research.


Personal

Ahlquist met his wife Dorothy Duff Ahlquist in
Seattle Seattle ( ) is a seaport city on the West Coast of the United States. It is the seat of King County, Washington. With a 2020 population of 737,015, it is the largest city in both the state of Washington and the Pacific Northwest region o ...
.


Death

Ahlquist died on April 15, 1983 in Augusta,
Georgia Georgia most commonly refers to: * Georgia (country), a country in the Caucasus region of Eurasia * Georgia (U.S. state), a state in the Southeast United States Georgia may also refer to: Places Historical states and entities * Related to the ...


References


External links


Biography on southalabama.edu
{{DEFAULTSORT:Ahlquist, Raymond P. 1914 births 1983 deaths 20th-century scientists American people of Swedish descent Recipients of the Lasker-DeBakey Clinical Medical Research Award American pharmacologists