Molecular Pharmacology, Vol 12, 987-998, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Morphine-like Peptides, Leucine Enkephalin and Methionine Enkephalin: Interactions with the Opiate Receptor

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

The morphine-like peptides leucine enkephalin and methionine enkephalin compete for opiate receptor binding with affinities resembling that of morphine. In the absence of added sodium, methionine enkephalin is about twice as potent as leucine enkephalin in reducing [³H]naloxone binding, whereas binding of the agonist [³H]dihydromorphine is reduced equally by the two enkephalins. Sodium decreases competition by both enkephalins for [³H]naloxone, but with twice as great an effect on leucine enkephalin as on methionine enkephalin. In contrast, competition by the enkephalins for [³H]dihydromorphine binding is enhanced by sodium. Manganese increases the apparent affinities of both leucine and methionine enkephalins for the opiate receptor. Incubations exceeding 20 min at 25° and 5 min at 37° result in a marked apparent degradation of both leucine and methionine enkephalins, which can be prevented by bacitracin.

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ACKNOWLEDGMENTS The authors thank Drs. D. Hauser and F. Cardinaux, Sandoz, Basel, for samples of enkephalin. They also thank Adele M. Snowman for superb technical assistance, and Dr. Richard Miller for advice on enhancing bacitracin effects.