Following the subcutaneous administration of R(-)N6-(2-phenylisopropyl)adenosine (600 nmol/kg/hr) to rats for 1 week using Alzet® mini-osmotic pumps, A1 adenosine receptor functions were determined using [3H]DPCPX binding, GTP(γ)S 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(γ)S 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(γ)S binding to G proteins is a suitable tool in studying the receptor regulation including desensitization.
|Number of pages||8|
|Journal||Korean Journal of Pharmacology|
|Publication status||Published - 1996|
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