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Molecular Pharmacology, Vol 13, 662-670, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Adenosine-Sensitive Adenylate Cyclase in Rat Striatal Homogenates and Its Relationship to Dopamine- and Ca2+-Sensitive Adenylate Cyclases

JOËL PRÉMONT 1, MICHÈLE PEREZ 1, and JOËL BOCKAERT 1

1 Laboratoires de Physiologie Cellulaire, 75231 Paris Cedex 05, France

Rat striatal homogenates were found to contain adenosine-sensitive adenylate cyclase, which could be fully stimulated by endogenous adenosine under standard adenylate cyclase assay conditions. Adenosine present in the adenylate cyclase assay had two origins, the homogenate and ATP hydrolysis during incubation. Theophylline, caffeine, and isobutylmethylxanthine inhibited the adenosine-sensitive adenylate cyclase. At low concentrations, theophylline inhibition was competitive (KI = 20 µM). The adenosine present in the assay could be removed by using adenosine deaminase. It was then possible to stimulate the adenosine-sensitive adenylate cyclase by adenosine analogues resistant to adenosine deaminase treatment, such as 2-chloroadenosine, N6-phenylisopropyladenosine, and 5'-deoxyadenosine, which was a partial agonist. Adenine, inosine, 5'-AMP, and ATP were neither agonists non antagonists. In addition to adenosine-sensitive adenylate cyclase, rat striatal homogenates contain Ca2+- and dopamine-sensitive adenylate cyclases. Each of these three adenylate cyclase systems was found to be independent of the others.

Note:
ACKNOWLEDGMENTS We are indebted to Drs. J. P. Tassin, A. M. Thierry, and J. Glowinski for their helpful criticisms of this work, and to Miss M. Dreyfus and Mrs. M. Guérin for their help in the preparation of the manuscript.

Submitted on December 23, 1976
Accepted on February 28, 1977




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