Structure-function analysis of inhibitory adenosine receptor regulation

Pharmacological and molecular cloning studies have revealed the presence of four adenosine receptor (AR) subtypes, termed A(1), A(2A), A(2B) and A(3). Given that the A(1) and A(3)ARs can both bind adenosine and couple productively to inhibitory G-proteins, the significance of the existence of multiple inhibitory AR subtypes remains obscure, although one possibility is that these receptors are regulated in a subtype-specific manner. In this review, we summarize our investigations into the mechanisms underlying the agonist-induced desensitization of inhibitory AR function. The results of this work demonstrate that while the A(1)AR desensitizes slowly over a time course of several hours, the A(3)AR desensitizes within minutes of agonist exposure. Molecular biological studies have begun to delineate the structural requirements responsible for these differences, and will provide a basis for future experiments designed to determine whether the ability of an inhibitory AR receptor subtype to 'turn-off' at a specific rate has implications for the physiological role of that receptor. (C) 1997 Elsevier Science Ltd.