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  • Title: Effects of an enkephalinase inhibitor on esophageal motility in man.
    Author: Chaussade S, Hamm R, Lecomte JM, Couturier D, Guerre J.
    Journal: Gastroenterol Clin Biol; 1988 Nov; 12(11):793-6. PubMed ID: 3220232.
    Abstract:
    Enkephalins are short lived peptides which are rapidly cleaved by 2 membrane peptidases: an enkephalinase and a carboxypeptidase. Enkephalin-like immuno-reactivity has been demonstrated in the smooth muscle and in the myenteric plexus of the human lower esophageal sphincter (LES). Opioid receptors have been found in the gastrointestinal tract and recently an enkephalin analog has been shown to inhibit LES relaxation and modify the peristaltic progression of the esophageal contractions. Acetorphan is an enkephalinase inhibitor which prevents, at least to some extent, the hydrolysis of endogenous enkephalins. Thus, the present work was designed to study the effect of acetorphan on esophageal motility. Ten healthy volunteers (mean age: 23 years) were studied. On 2 separate days, each subject received in random order acetorphan (2.5 mg/kg intravenously at a constant rate in 20 min) or placebo. Esophageal manometry was performed with a Dentsleeve. Wet swallows (5 ml) were performed at 1 min intervals during 80 min and results were pooled in 10 min periods. Acetorphan inhibited significantly (p less than 0.02) LES relaxation 20 min after the beginning of the infusion and throughout the study. The maximal effect occurred 50 min after the beginning of acetorphan infusion and LES relaxation (m +/- SEM) was reduced from 92 +/- 2.6 to 79.5 +/- 2.9 p. 100 (p less than 0.01). Duration, amplitude, and velocity of esophageal contractions were not modified. Acetorphan an enkephalinase inhibitor, is able to reproduce the effect of IV exogenous enkephalins on LES relaxation in man. This result suggest that endogenous enkephalins might play a role in the normal control of the LES relaxation.
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