Raymond P. Ahlquist

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[4] 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: "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."[4]

The publication was initially dismissed, but went on to have a major impact on pharmacology.[3][5] 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.[3][5] 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.[5][6]

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[7] 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.[8]

In his most recent essay in 1980, he looked back to the 1948 publication.[9] The impact of the 1948 publication is evident by the number of times it has been cited (2766 times as of 2011).