ABSTRACT
The discovery of cyclic AMP by Sutherland and Rail (1) in 1956 provided the initial impetus from which the scaffolding of drug receptor pharmacology with the discipline of physiology was extended to include biochemical assessment of receptor-promoted drug action. Receptor activation subsequently has been described in increasingly molecular terms, and the often inexact approach of measuring drug-receptor interactions at the intact animal or intact tissue level now can be complemented by inherently more precise approaches associated with direct biochemical assay of receptor responses. A major chapter in the history of drug development in the first half of this century involved discovery of molecules that mimic or block the effects of biogenic amines at their cognate receptors. The initial biochemical observation of an agonist-receptor interaction by Sutherland and Rail (1) was made for the biogenic amine epinephrine, and the elucidation of the biochemical basis of the glycogenolytic effects of ,8-adrenoceptor activation in the liver proved a harbinger of eventual identification of similar adenylyl cyclase-activating responses to many other receptors (2). Promotion of other second-messenger signaling responses, e.g., activation of guanylyl cyclase or phospholipase C and inhibition of adenylyl cyclase, subsequently
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