Activation and desensitization of rat A3-adenosine receptors by selective adenosine derivatives and xanthine-7-ribosides

Kyung Sun Park, Carsten Hoffmann, Hea Ok Kim, William L. Padgett, John W. Daly, Roberta Brambilla, Cristina Motta, Maria P. Abbracchio, Kenneth A. Jacobson

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Xanthine and adenosine derivatives, known to bind to recombinant rat A3 adenosine receptors stably expressed in Chinese hamster ovary cells, were characterized in a functional assay consisting of activation of A3 receptor- stimulated binding of [35S]GTPγS in rat RBL-2H3 cell membranes 1,3- Dibutylxanthine-7-riboside-5'-N-methylcarboxamide (DBXRM, 7b), previously shown to inhibit adenylyl cyclase via rat A3 receptors with full efficacy, appeared to be a partial agonist at the rat A3 receptor of RBL-2H3 cells. Full agonists, such as CI-IB-MECA or I-AB-MECA, were more potent and effective than the partial agonist DBXRM in causing desensitization of rat A3 receptors, as indicated by loss of [35S]GTPγS binding. At A1 receptors, antagonism of agonist-elicited inhibition of rat adipocyte adenylyl cyclase was observed for several xanthine-7-riboside derivatives that had been shown to be full agonists at rat A3 receptors. A new xanthine riboside (3'-deoxyDBXRM, 7c) was synthesized and found to be a partial agonist at rat A3 receptors and an antagonist at rat A1 receptors. Thus, it is possible for the same compound to stimulate one adenosine receptor subtype (A3) and block another subtype (A1) within the same species.

Original languageEnglish (US)
Pages (from-to)97-105
Number of pages9
JournalDrug Development Research
Issue number2-3
StatePublished - Jun 1998
Externally publishedYes


  • Adenosine derivatives
  • Adenylyl cyclase
  • Guanine nucleotides
  • Nucleosides
  • Xanthines

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology


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