Regulation of Al adenosine receptors EM cerebellar granule cells

B. D. Hettinyer-Smith, M. Leid, Thomas F. Murray

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Abstract

Adenosine, a central nervous system neuromodulator, acts via Al, A2a, A2b and A3 adenosine receptors which are members of the G protein coupled receptor superfamily. Al adenosine receptors (AI AR) are coupled to the inhibition of adenylyl cyclase. Primary cultures of cerebellar granule cells from 8 day old Sprague Dawley rat pups were established and used to study Al AR regulation in response to chronic exposure to agonists, antagonists, forskolin and dexamethasone. Treatment of cells for 72 hours with the A1AR agonist, cyclopentyladenosine (CPA) resulted in a decrease in Bmax while the receptor affinity remained unchanged, as measured by saturation binding with the AI AR selective antagonist, [3H]dipropylcyclopentylxanthine. Additionally, CPA treatment resulted in a loss of sensitivity to A1AR agonist-induced inhibition of adenylyl cyclase. Chronic antagonism of A1 AR by 8-parasulfophenyltheophylline resulted in an increase in Bmax as well as a sensitization of the A l AR agonist-induced adenylyl cyclase inhibition. In order to assess the role of cAMP in receptor regulation, cells were treated with forskolin. Forskolin exposure did not affect AI AR density or affinity. These results indicate that intracellular cAMP does not modulate the expression of AI AR. In contrast dexamethasone exposure effected an upregulation of A1AR in cerebellar granule cells. These data suggest that the promoter region of the AI AR may possess a steroid but not a cAMP response element. (Supported by NIDA grant F31 DA05631-02 to BBS).

Original languageEnglish
JournalFASEB Journal
Volume10
Issue number3
Publication statusPublished - 1996
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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