흰쥐 대뇌피질에서 A₁ 아데노신 수용체의 탈감작

Desensitization of A₁ Adenosine Receptors in Rat Cerebral Cortex

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]GTP_γS 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]GTP_γS 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]GTP_γS binding to G proteins is a suitable tool in studying the receptor regulation including desensitization