Cyclopentyladenosine-induced homologous down-regulation of A1 adenosine receptors (A1AR) in intact neurons is accompanied by receptor sequestration but not a reduction in A1AR mRNA expression or G protein alpha-subunit content

J Neurochem. 1998 Jul;71(1):221-30. doi: 10.1046/j.1471-4159.1998.71010221.x.


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 inhibition. We have now determined that A1AR-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 microM cyclopentyladenosine. Expression of G protein alpha-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 A1AR 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / metabolism
  • Animals
  • Cells, Cultured
  • Cerebellum / cytology
  • Down-Regulation / drug effects
  • GTP-Binding Protein alpha Subunits, Gs / metabolism
  • Gene Expression / drug effects
  • Neurons / chemistry*
  • Neurons / drug effects
  • Neurons / enzymology
  • Purinergic P1 Receptor Agonists
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P1 / genetics*
  • Receptors, Purinergic P1 / metabolism*
  • Theophylline / analogs & derivatives
  • Theophylline / pharmacology
  • Tritium
  • Xanthines / pharmacology


  • Adenylyl Cyclase Inhibitors
  • Purinergic P1 Receptor Agonists
  • RNA, Messenger
  • Receptors, Purinergic P1
  • Xanthines
  • Tritium
  • N(6)-cyclopentyladenosine
  • 8-(4-sulfophenyl)theophylline
  • 1,3-dipropyl-8-cyclopentylxanthine
  • Theophylline
  • GTP-Binding Protein alpha Subunits, Gs
  • Adenylyl Cyclases
  • Adenosine