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Molecular Pharmacology, Vol 18, 598-601, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Adenosine Receptor-Mediated Inhibition of Rat Cerebral Cortical Adenylate Cyclase by a GTP-Dependent Process

DERMOT M. F. COOPER 1, CONSTANTINE LONDOS 1, and MARTIN RODBELL 1

1 Section on Membrane Regulation, Laboratory of Nutrition and Endocrinology, National Institute of Arthritis, Metabolism and Digestive Diseases, National Institutes of Health, Building 6, Room B1-10, Bethesda, Maryland 20205

Adenosine analogues inhibit rat cerebral cortical adenylate cyclase by a receptor-mediated GTP-dependent process. N6-Phenylisopropyladenosine and other analogues of adenosine are potent inhibitors (Ki values of 10-100 nM) of adenylate cyclase in a particulate preparation of rat cerebral cortex. The detection of such inhibitory effects is facilitated by the use of a deoxy ATP assay system. The inhibition is strictly dependent on GTP, is amplified by Na+ ions, and is antagonized by methylxanthines.

Note:
ACKNOWLEDGMENTS The authors wish to thank Drs. John Daly and Bill Padgett for helpful discussions and advice on membrane preparations. The technical assistance of Mr. James Oden and the expert secretarial assistance of Ms. Bonnie Richards are also gratefully acknowledged.

Submitted on February 11, 1980
Accepted on June 27, 1980




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