Cell membrane receptors: gateway to endogenous medicinals

Some recent developments in the author's laboratory which rely upon the techniques of radioreceptor assays (RRA) for drugs and hormones are reviewed. These receptor studies have led, for example, to (a) the identification of 17-alpha estrogens that interact with the opiate receptor, (b) the delineation of a unique class of opiate receptor that mediates explosive motor behavior and is resistant to naloxone, (c) the discovery of progesterone derivatives and active tissue fractions that compete for specific binding sites for cardiac glycosides, (d) the observation that both the opiate and digitalis RRA's permit discrimination between classes of centrally active compounds that differ only trivially in their physicochemical properties but exert opposing actions on nerve excitability, and (e) the hypothesis that the correlation between lipid solubility and potency of general anesthetics applies to the accommodation of this class of drugs by hydrophobic crypts of membrane proteins and other proteins rather than to an ill-defined hydrophobic interaction with membrane lipid. Examples are given to demonstrate that the radioreceptor technique promises (a) to continue as a major contributing methodology in the design of pharmacological agents of greater specificity with respect to organ systems and neuronal pathways affected and, thus, of potential clinical usefulness, and (b) to expose as yet unidentified physiologically important humoral factors.