DESENSITIZATION OF ADENOSINE A(1) RECEPTOR-MEDIATED INHIBITION OF ADENYLYL-CYCLASE IN CEREBELLAR GRANULE CELLS

Agonist-induced desensitization of adenosine A(1) receptor-mediated in hibition of adenylyl cyclase has been studied in cerebellar granule ce lls. Exposure of cells to the adenosine A(1) receptor agonist R-phenyl isopropyl adenosine (R-PIA) from 2 to 48 h brings about desensitizatio n of this signal transduction pathway. Associated with the desensitiza tion process, a decrease in radioligand binding performed in intact ce lls with the adenosine A(1) receptor agonist [H-3]cyclohexyladenosine (CHA) has been detected. Simultaneously, an increase of adenosine A(1) radioligand binding has also been detected in microsomes. A decrease in the steady-state level of alpha-Gi in both, plasma membrane and mic rosomes also has been detected during the desensitization process. The se data may account for the desensitization of the inhibitory pathway of the adenylyl cyclase in cerebellar granule cells described herein. After a transient increase in adenosine A(1) receptor mRNA, no changes were observed in this parameter after 12 hr of treatment with the ade nosine A(1) agonist R-PIA, suggesting a post-transcriptional regulatio n of this receptor during long-term desensitization.