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Molecular Pharmacology

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Research ArticleArticle

Temperature and Ionic Influences on Opiate Receptor Binding

RABI SIMANTOV, ADELE M. SNOWMAN and SOLOMON H. SNYDER
Molecular Pharmacology November 1976, 12 (6) 977-986;
RABI SIMANTOV
Departments of Pharmacology and Experimental Therapeutics and Psychiatry and the Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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ADELE M. SNOWMAN
Departments of Pharmacology and Experimental Therapeutics and Psychiatry and the 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 Psychiatry and the Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Abstract

Treatment of brain membranes by preliminary incubation with sodium or at elevated temperature increases opiate receptor binding of both the agonist [3H]dihydromorphine and the antagonist [3H]naloxone about 2-fold. Enhancement of receptor binding is elicited by sodium but not potassium and cesium, which coincides with the ability of sodium selectively to accelerate dissociation of opiate agonists from receptor sites. Augmented receptor binding associated with elevated preliminary incubation temperature is antagonized markedly by manganese, to a lesser extent by magnesium, and not by calcium, which coincides with the selectivity of divalent cations in increasing opiate agonist binding. Elevated receptor binding produced by these treatments is associated with an increase in the number of binding sites, with minimal changes in affinity. The "new receptors" unmasked by these preliminary incubation conditions have an augmented sensitivity to degradation by protein-modifying reagents. The characteristics of preliminary incubation conditions that increase opiate receptor binding suggest that enhancement of binding is related to dissociation from the receptor of an endogenous inhibitor of binding with the characteristics of an opiate agonist. Regardless of preliminary incubation conditions, manganese reduces both [3H]naloxone and [3H]dihydromorphine binding at 0°, indicating a direct effect on the opiate receptor. The present observations emphasize the importance of defining experimental conditions for opiate receptor binding.

  • Copyright © 1976 by Academic Press, Inc.

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Molecular Pharmacology
Vol. 12, Issue 6
1 Nov 1976
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Research ArticleArticle

Temperature and Ionic Influences on Opiate Receptor Binding

RABI SIMANTOV, ADELE M. SNOWMAN and SOLOMON H. SNYDER
Molecular Pharmacology November 1, 1976, 12 (6) 977-986;

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Research ArticleArticle

Temperature and Ionic Influences on Opiate Receptor Binding

RABI SIMANTOV, ADELE M. SNOWMAN and SOLOMON H. SNYDER
Molecular Pharmacology November 1, 1976, 12 (6) 977-986;
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