We showed previously that exposure of cerebellar granule cells to the A1 adenosine receptor (A1AR)selective agonist, cyclopentyladenosine, decreases A1AR density and G protein coupling corresponding to blunted agonist- induced adenylyl cyclase (EC 18.104.22.168) inhibition. We have now determined that AiAR-mediated adenylyl cyclase inhibition was desensitized in a homologous manner. Carbachol- and baclofen-induced inhibition of adenylyl cyclase was unaffected by 48-h exposure to 10 μM cyclopentyladenosine. Expression of G protein α subunits was not affected dramatically by agonist exposure. The fraction of sequestered A1AR was increased significantly at 4, 24, and 48 h of cyclopentyladenosine exposure (35, 57, and 81% increase over control, respectively). The time course of agonist-induced A1AR sequestration was slower than that reported for other G protein-coupled receptors. Incubation with the adenosine receptor antagonist, 8-p-sulfophenyltheophylline or adenosine deaminase did not alter sequestration significantly. Neither steady-state AiAR mRNA levels nor transcript stability was affected by 48-h agonist exposure. We determined that A1AR half-life in cerebellar granule cells is 20.9 h, which is considerably longer than that reported for several other G protein-coupled receptors. The slow time course of A1AR sequestration and the stability of the corresponding mRNA may be a reflection of the tonic inhibitory tone exerted by adenosine in brain.
|Original language||English (US)|
|Number of pages||10|
|Journal||Journal of Neurochemistry|
|State||Published - Jul 1 1998|
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience