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Molecular Pharmacology, Vol 16, 700-708, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Serotonin Receptor Binding Sites Affected Differentially by Guanine Nucleotides

STEPHEN J. PEROUTKA 1, RICHARD M. LEBOVITZ 1, and SOLOMON H. SNYDER 1

1 Departments of Pharmacology and Experimental Therapeutics and Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Guanosine triphosphate (GTP) and diphosphate (GDP) decrease the binding of the agonist [3H]serotonin (5-HT) to serotonin receptors in mammalian brain membranes. Binding of the antagonist [3H]spiroperidol is not affected by guanine nucleotides while the mixed agonist-antagonist [3H]lysergic acid diethylamide ([3H]LSD) is affected in an intermediate manner. GTP lowers the apparent affinity of [3H]5-HT for its receptors without changing the number of binding sites. Both the association and dissociation rates of [3H]5-HT are increased by GTP. The potency of 5-HT agonists in competing for [3H]5-HT but not [3H]LSD or [3H]spiroperidol binding sites is decreased by GTP. Competition by partial agonists and antagonists for [3H]5-HT binding sites is not affected by GTP.

Note:
ACKNOWLEDGMENTS We thank Pamela Morgan for manuscript preparation.

Submitted on April 16, 1979
Accepted on July 5, 1979




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Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics