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Cyclopentyladenosine‐Induced Homologous Down‐Regulation of A 1 Adenosine Receptors (A 1 AR) in Intact Neurons Is Accompanied by Receptor Sequestration but Not a Reduction in A 1 AR mRNA Expression or G Protein α‐Subunit Content
Author(s) -
Hettinger Barbara D.,
Leid Mark,
Murray Thomas F.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71010221.x
Subject(s) - adenylyl cyclase , adenosine , adenosine a1 receptor , medicine , endocrinology , agonist , cgs 21680 , chemistry , adenosine receptor , biology , receptor , biochemistry , stimulation
We showed previously that exposure of cerebellar granule cells to the A 1 adenosine receptor (A 1 AR)‐selective agonist, cyclopentyladenosine, decreases A 1 AR density and G protein coupling corresponding to blunted agonist‐induced adenylyl cyclase (EC 4.6.1.1) inhibition. We have now determined that A 1 AR‐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 µ M cyclopentyladenosine. Expression of G protein α‐subunits was not affected dramatically by agonist exposure. The fraction of sequestered A 1 AR 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 A 1 AR 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 A 1 AR mRNA levels nor transcript stability was affected by 48‐h agonist exposure. We determined that A 1 AR 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 A 1 AR sequestration and the stability of the corresponding mRNA may be a reflection of the tonic inhibitory tone exerted by adenosine in brain.