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Research ArticleArticle

Opiate Receptor Binding: Enzymatic Treatments That Discriminate between Agonist and Antagonist Interactions

GAVRIL W. PASTERNAK and SOLOMON H. SNYDER
Molecular Pharmacology July 1975, 11 (4) 478-484;
GAVRIL W. PASTERNAK
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

Several enzymatic treatments differentially influence receptor binding of opiate agonists and antagonists. Low concentrations of trypsin (EC 3.4.4.4), chymotrypsin (EC 3.4.4.5), and phospholipase A (EC 3.1.1.4) reduce receptor binding of agonists more than that of antagonists, while phospholipases C (EC 3.1.4.3) and D (EC 3.1.4.4) and neuraminidase (EC 3.2.1.18) have negligible influence on the binding of agonists or antagonists. Binding of the opiate agonist [3H]dihydromorphine is more sensitive to inhibition by enzymatic treatments when assays are conducted in the presence than in the absence of sodium. Moreover, enzymatic treatments markedly reduce the concentrations of sodium required to inhibit [3H]dihydromorphine binding. The extent of reduction of [3H]dihydromorphine binding by enzymatic treatment correlates closely with the sensitivity of [3H]dihydromorphine to sodium. These observations suggest that a major action of enzymatic treatments is to enhance the sensitivity of opiate agonist binding to sodium.

ACKNOWLEDGMENTS We thank Mr. Robert Warren for his contributions to the initial phases of this study, and Mrs. Adele Snowman for her excellent technical assistance. We also thank Drs. P. Cuatrecasas, D. Coffey, I. Parikh, and P. Talalay for helpful discussions.

  • Copyright ©, 1975, by Academic Press, Inc.

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Molecular Pharmacology
Vol. 11, Issue 4
1 Jul 1975
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Research ArticleArticle

Opiate Receptor Binding: Enzymatic Treatments That Discriminate between Agonist and Antagonist Interactions

GAVRIL W. PASTERNAK and SOLOMON H. SNYDER
Molecular Pharmacology July 1, 1975, 11 (4) 478-484;

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Research ArticleArticle

Opiate Receptor Binding: Enzymatic Treatments That Discriminate between Agonist and Antagonist Interactions

GAVRIL W. PASTERNAK and SOLOMON H. SNYDER
Molecular Pharmacology July 1, 1975, 11 (4) 478-484;
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