Dynamic involvement of the inducible type of nitric oxide synthase in acid-induced duodenal mucosal alkaline secretion in the rat

It has previously been shown that mucosal nitric oxide synthase (NOS) is in volved in acid-induced duodenal mucosal alkaline secretion. The primary aim of the present study was to elucidate which isoform of NOS is responsible in rats. Immunohistochemistry showed that inducible NOS (iNOS) was constitu tively expressed in villous epithelial cells. Exposing the duodenal mucosa to 10 mM HCl resulted in an increased duodenal mucosal alkaline secretion. This response was totally inhibited by intraluminal administration of a sel ective inhibitor of iNOS (L-N-6-1-iminoethyl-lysine). One hour after the ac id exposure, western blot technique showed a marked increase in mucosal iNO S expression. A second acid exposure resulted in a further stimulation of a lkaline secretion. These data suggest that exposure of the duodenal mucosa to HCl initiates an increased mucosal alkaline secretion, via NO synthesis mediated by iNOS located in the epithelial cells of the villi. In addition, luminal acid stimulates expression of iNOS.