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

✍ Scribed by Kyung-sun Park; Carsten Hoffmann; Hea Ok Kim; William L. Padgett; John W. Daly; Roberta Brambilla; Cristina Motta; Maria P. Abbracchio; Kenneth A. Jacobson

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 212 KB
• Volume: 44
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/(sici)1098-2299(199806/07)44:2/3<97::aid-ddr7>3.0.co;2-5

✦ Synopsis

Xanthine and adenosine derivatives, known to bind to recombinant rat A 3 adenosine receptors stably expressed in Chinese hamster ovary cells, were characterized in a functional assay consisting of activation of A 3 receptor-stimulated binding of [ 35 S]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 A 3 receptors with full efficacy, appeared to be a partial agonist at the rat A 3 receptor of RBL-2H3 cells. Full agonists, such as Cl-IB-MECA or I-AB-MECA, were more potent and effective than the partial agonist DBXRM in causing desensitization of rat A 3 receptors, as indicated by loss of [ 35 S]GTPγS binding. At A 1 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 A 3 receptors. A new xanthine riboside (3′-deoxyDBXRM, 7c) was synthesized and found to be a partial agonist at rat A 3 receptors and an antagonist at rat A 1 receptors. Thus, it is possible for the same compound to stimulate one adenosine receptor subtype (A 3 ) and block another subtype (A 1 ) within the same species.