Vol. 280, Issue 5, G890-G896, May 2001
MEK inhibits secretin release and pancreatic
secretion: roles of secretin-releasing peptide and
somatostatin
James P.
Li,
Kae Yol
Lee,
Ta-Min
Chang, and
William
Y.
Chey
Konar Center for Digestive and Liver Diseases, University of
Rochester Medical Center, Rochester, New York 14642
We investigated the
mechanism of action of methionine enkephalin (MEK) on HCl-stimulated
secretin release and pancreatic exocrine secretion.
Anesthetized rats with pancreatobiliary cannulas and isolated upper
small intestinal loops were perfused intraduodenally with 0.01 N HCl
while bile and pancreatic juice were diverted. The effect of
intravenous MEK on acid-stimulated secretin release and pancreatic
exocrine secretion was then studied with or without coinfusion of
naloxone, an anti-somatostatin (SS) serum, or normal rabbit serum.
Duodenal acid perfusate, which contains secretin-releasing peptide
(SRP) activity, was collected from donor rats with or without
pretreatment with MEK, MEK + naloxone, or MEK + anti-SS serum, concentrated by ultrafiltration, and neutralized. The
concentrated acid perfusate (CAP), which contains SRP bioactivity, was
infused intraduodenally into recipient rats. MEK increased plasma SS
concentration and inhibited secretin release and pancreatic fluid and
bicarbonate secretion dose-dependently. The inhibition was partially
reversed by naloxone and anti-SS serum but not by normal rabbit serum. In recipient rats, CAP increased plasma secretin level and pancreatic secretion. CAP SRP bioactivity decreased when it was collected from
MEK-treated donor rats; this was partially reversed by coinfusion with
naloxone or anti-SS serum. These results suggest that in the rat, MEK
inhibition of acid-stimulated pancreatic secretion and secretin release
involves suppression of SRP activity release. Thus the MEK inhibitory
effect appears to be mediated in part by endogenous SS.
naloxone; anti-somatostatin serum; rats; fluid; bicarbonate
secretion
