Effects of an XXXX inhibitor on esophageal motility in @entity1 .

@entity1 @entity19353 @entity2282
Enkephalins are short lived peptides which are rapidly cleaved by 2 membrane peptidases: an @entity2282 and a carboxypeptidase. Enkephalin-like immuno-reactivity has been demonstrated in the smooth muscle and in the myenteric plexus of the @entity1 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. @entity19353 is an @entity2282 inhibitor which prevents, at least to some extent, the hydrolysis of endogenous enkephalins. Thus, the present work was designed to study the effect of @entity19353 on esophageal motility. Ten healthy volunteers (mean age: 23 years) were studied. On 2 separate days, each subject received in random order @entity19353 (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. @entity19353 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 @entity19353 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. @entity19353 an @entity2282 inhibitor, is able to reproduce the effect of IV exogenous enkephalins on LES relaxation in @entity1 . This result suggest that endogenous enkephalins might play a role in the normal control of the LES relaxation.
