ABSTRACT
Receptors, now recognized as chemical entities, began life as a late-19thcentury concept, proposed independently by Ehrlich and Langley. There seems to have been little enthusiasm for the concept at the beginning. Indeed, Henry Dale, the doyen of British physiologists, thought the idea was redundant. However, the concept was kept alive by a small coterie of theoretically minded pharmacologists who were interested in trying to interpret dose-response relations. Hill, a pupil of Langley, sought to interpret the dose-response curves generated by nicotine on the frog rectus abdominis preparation by applying the Law of Mass Action. To make the algebra work, he had to turn the receptor concept into a mathematical operator. That was in 1906. Over the next 50 years, quantitative pharmacology was quietly developed on the basis of the receptor-as-mathematicaloperator concept. Although the theoretical work of Clark, Gaddum, Schild, Ariens, Furchgott, and others was not ignored by mainstream pharmacologists and textbook writers, neither was it incorporated into their work until after 1950. Ahlquist complained that he failed to get his 1948 paper on adrenotropic receptors published in any of the main pharmacology journals and only succeeded in getting it published in the American Journal of Physiology because the editor, W. F. Hamilton, was a friend and colleague. Yet Ahlquist's paper was the first time that "receptor" was used as an explanatory model, was the start of the enthusiasm among pharmacologists for classification of receptor subtypes, and, as it happens, was the foundation of my own work on beta-blockers.
