Molecular Pharmacology, Vol 11, 340-351, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Differential Effects of Protein-Modifying Reagents on Receptor Binding of Opiate Agonists and Antagonists

¹ Departments of Pharmacology and Experimental Therapeutics and Psychiatry and the Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Opiate receptor binding is enhanced by prior incubation, which removes an endogenous inhibitor of receptor binding. Protein-modifying reagents which affect sulfhydryl groups differentially influence the binding of agonists and antagonists to the opiate receptor. These reagents, including iodoacetamide, N-ethylmaleimide, mercuriacetate, mersalyl acid, p-aminophenylmercuric acetate, and p-chloromercuribenzoate, strongly inhibit [³H]dihydromorphine binding at concentrations which do not affect [³H]naloxone binding. Prior treatment with opiates protects the receptor binding from reagents. The reagents decrease the apparent number of dihydromorphine binding sites without altering their affinity, and also increase the sensitivity of agonist binding to the inhibitory effects of sodium.

Note:
ACKNOWLEDGMENT The authors are grateful to Adele Snowman for her inspired technical assistance.

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