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Molecular Pharmacology

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Research ArticleArticle

Selective Enhancement of [3H]Opiate Agonist Binding by Divalent Cations

GAVRIL W. PASTERNAK, ADELE M. SNOWMAN and SOLOMON H. SNYDER
Molecular Pharmacology November 1975, 11 (6) 735-744;
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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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

Manganese ions enhance binding of the tritiated opiate agonists dihydromorphine and levorphanol 78% and 64%, respectively, while binding of the tritiated antagonists naloxone, levallorphan, and diprenorphine is unaffected. Magnesium and nickel ions also selectively enhance [3H]dihydromorphine binding with no effect on [3H]naloxone binding. By contrast, cupric and ferrous ions lower the binding of [3H]dihydromorphine far more than that of [3H]naloxone. Manganese ions also enhance the ability of unlabeled agonists to inhibit the binding of [3H]naloxone. All these effects are most pronounced in the presence of sodium chloride. Ethylenediaminetetracetic acid inhibits the binding of [3H]dihydromorphine 50% without altering [3H] naloxone binding, while ethylenebis[(oxyethylenenitrilo)]tetraacetic acid and magnesium and manganese complexes of EDTA are ineffective. The EDTA effect can be reversed by subsequent addition of either manganese or magnesium ions. The divalent cations which enhance opiate agonist binding appear to counteract the ability of sodium ions to inhibit agonist binding selectively. The potency of sodium in inhibiting [3H]dihydromorphine binding is reduced 5-fold by the addition of manganese ions. There is a good correlation between the sensitivity of opiate receptor binding to sodium and manganese.

ACKNOWLEDGMENT We thank Mr. Marty Katz for his contribution to the initial phases of this study.

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

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Molecular Pharmacology
Vol. 11, Issue 6
1 Nov 1975
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Research ArticleArticle

Selective Enhancement of [3H]Opiate Agonist Binding by Divalent Cations

GAVRIL W. PASTERNAK, ADELE M. SNOWMAN and SOLOMON H. SNYDER
Molecular Pharmacology November 1, 1975, 11 (6) 735-744;

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Research ArticleArticle

Selective Enhancement of [3H]Opiate Agonist Binding by Divalent Cations

GAVRIL W. PASTERNAK, ADELE M. SNOWMAN and SOLOMON H. SNYDER
Molecular Pharmacology November 1, 1975, 11 (6) 735-744;
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