Elevated levels of enkephalin in morphine-dependent rats

Abstract

NUMEROUS theories propose mechanisms regulating opiate dependence. Hughes1,2 elegantly identified a morphine-like factor “enkephalin” which mimics effects of morphine on nerve, plexus in smooth muscle in a fashion that can be antagonised by opiate antagonists, while a compound with the same properties has been identified in brain extracts by competition for opiate receptor binding3–6. Enkephalin activity has a regional and subcellular distribution similar to that of the opiate receptor7,8 and was first shown to be a mixture of two peptides H–Tyr–Gly–Gly–Phe–Met–OH and H–Tyr–Gly–Gly–Phe–Leu–OH by Hughes et al.9 with a preponderance of the methionine peptide in pig brain9. Independently, we identified the same two peptides in bovine brain but with four times more of the leucine than of the methionine peptide10,11. Brain enkephalin differs from substances in pituitary gland and hypothalamic extracts which mimic morphine12,13.

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