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Research ArticleArticle

The Effect of Disulfide Bond Reduction on the Properties of Cholinergic Receptors in Chick Muscle

H. P. RANG and J. M. RITTER
Molecular Pharmacology November 1971, 7 (6) 620-631;
H. P. RANG
University Department of Pharmacology, Oxford, England
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J. M. RITTER
University Department of Pharmacology, Oxford, England
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Abstract

The effect of treatment with the disulfide bond-reducing agent dithiothreitol on the responsiveness of isolated strips of chick muscle to cholinergic agonists and antagonists has been studied. After reduction, the muscle became less sensitive to carbachol, acetylcholine, and several other monoquaternary agonists, but more sensitive to bisquaternaries of the decamethonium series with chain lengths from C6 to C9. Hexamethonium, normally a weak antagonist, became an agonist. The relation between chain length and potency within two homologous series was only slightly modified by reduction of the receptors. The effects of reduction could be fully reversed by reoxidation with 5,5'-dithiobis(2-nitrobenzoic acid). The stimulant actions of caffeine and potassium ions were unaffected by reduction. Tubocurarine did not protect the receptors against the action of dithiothreitol.

Reduction increased the affinity of tubocurarine for the receptors, by a factor of 2.4. It also greatly increased the blocking potency of the alkylating agent diphenyldecamethonium mustard and, to a smaller extent, that of the corresponding dinaphthyl compound.

These results, which are comparable to those obtained on electroplax cells, suggest that the receptor possesses a disulfide bond, reduction of which modifies the selectivity of the receptor without markedly affecting its function.

  • Copyright ©, 1971, by Academic Press, Inc.

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Molecular Pharmacology
Vol. 7, Issue 6
1 Nov 1971
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Research ArticleArticle

The Effect of Disulfide Bond Reduction on the Properties of Cholinergic Receptors in Chick Muscle

H. P. RANG and J. M. RITTER
Molecular Pharmacology November 1, 1971, 7 (6) 620-631;

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Research ArticleArticle

The Effect of Disulfide Bond Reduction on the Properties of Cholinergic Receptors in Chick Muscle

H. P. RANG and J. M. RITTER
Molecular Pharmacology November 1, 1971, 7 (6) 620-631;
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