Agonist-induced desensitization of adenosine A(1) receptor-mediated inhibition of adenylyl cyclase has been studied in cerebellar granule cells. Exposure of cells to the adenosine A(1) receptor agonist R-phenylisopropyl adenosine (R-PIA) from 2 to 48 h brings about desensitization of this signal transduction pathway. Associated with the desensitization process, a decrease in radioligand binding performed in intact cells 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 microsomes also has been detected during the desensitization process. These 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 adenosine A(1) agonist R-PIA, suggesting a post-transcriptional regulation of this receptor during long-term desensitization.
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|Titolo:||Desensitization of adenosine A(1) receptor-mediated inhibition of adenylyl cyclase in cerebellar granule cells|
SANZ MOLINA, Juana Maria (Secondo)
|Data di pubblicazione:||1998|
|Appare nelle tipologie:||03.1 Articolo su rivista|