Pharmacological and molecular cloning studies have revealed the presen
ce 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, althoug
h one possibility is that these receptors are regulated in a subtype-s
pecific manner. In this review, we summarize our investigations into t
he mechanisms underlying the agonist-induced desensitization of inhibi
tory 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 biolog
ical studies have begun to delineate the structural requirements respo
nsible for these differences, and will provide a basis for future expe
riments 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 Lt
d.