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Research ArticleArticle

Serotonin and Lysergic Acid Diethylamide Binding in Rat Brain Membranes: Relationship to Postsynaptic Serotonin Receptors

JAMES P. BENNETT JR. and SOLOMON H. SNYDER
Molecular Pharmacology May 1976, 12 (3) 373-389;
JAMES P. BENNETT JR.
Departments of Pharmacology and Experimental Therapeutics and of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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SOLOMON H. SNYDER
Departments of Pharmacology and Experimental Therapeutics and of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Abstract

[3H]Serotonin (5-HT) binds to membrane preparations of rat brain in a saturable fashion and with substrate specificity and regional variations consistent with its binding to the postsynaptic serotonin receptor. The dissociation constant for [3H]5-HT binding is about 8 nM, and the total number of 5-HT binding sites in the brain is 16 pmoles/g of tissue, wet weight. There is considerable structural specificity in the affinity of various tryptamines for the [3H]5-HT binding sites, with a crucial role played by the 5-hydroxy substituent. d-[3H]Lysergic acid diethylamide (LSD) binding sites have substrate specificity requirements similar to the [3H]5-HT binding sites, but the 5-hydroxy substituent is less critical. 5-HT and related agonists have about 100 times more affinity for 5-HT than LSD binding sites, while classical 5-HT antagonists have 4-100 times greater affinity for LSD binding sites. LSD itself has a similar affinity for 5-HT and LSD binding sites. Raphe lesions which result in degeneration of 5-HT neurons do not lower [3H]5-HT binding, indicating that binding does not take place to presynaptic 5-HT neurons. Regional variations in serotonin and LSD binding are fairly similar. Highest binding occurs in the corpus striatum, hippocampus, and cerebral cortex, with lowest binding in the cerebellum. The ontogeny of 5-HT and LSD binding sites is nearly identical and does not appear to depend on functionally intact presynaptic 5-HT neuronal input.

ACKNOWLEDGMENTS We gratefully acknowledge the dedicated technical assistance of Gregory Mack.

  • Copyright © 1976 by Academic Press, Inc.

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Molecular Pharmacology
Vol. 12, Issue 3
1 May 1976
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Research ArticleArticle

Serotonin and Lysergic Acid Diethylamide Binding in Rat Brain Membranes: Relationship to Postsynaptic Serotonin Receptors

JAMES P. BENNETT and SOLOMON H. SNYDER
Molecular Pharmacology May 1, 1976, 12 (3) 373-389;

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Research ArticleArticle

Serotonin and Lysergic Acid Diethylamide Binding in Rat Brain Membranes: Relationship to Postsynaptic Serotonin Receptors

JAMES P. BENNETT and SOLOMON H. SNYDER
Molecular Pharmacology May 1, 1976, 12 (3) 373-389;
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