Following the subcutaneous administration of R(-)N6-(2-phenylisopropyl)adenosine(600 nmol/kg/hr) to rats for 1 week using tAlzet？？ mini-osmotic pumps, A1 adenosine receptor functions were determined using [3H]DPCPX binding, [35S]GTPγS binding, and adenylyl cyclase assays. A1 adenosine receptor binding and the inhibition of adenylyl cyclase activity by PIA was not altered in cerebrocortical membranes prepared from PIA-treated rats. However, there was a significant decrease in the A1 adenosine receptor-mediated stimulation of [35S]GTPγS binding to cerebrocortical membranes prepared from PIA-treated rats(22.0% decrease in basal activity; 19.7% decrease in maximal activity). These results suggest that the desensitization of A1 adenosine receptors following chronic administration involves agonist-induced uncoupling of the receptors from G proteins rather than alteration of A1 adenosine receptor molecules. It is also suggested that the determination of stimulation of [35S]GTPγS binding to G proteins is a suitable tool in studying the receptor regulation including desensitization
