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Duodenal HCO3− secretion increases in response to luminal acid, mediated by endogenous nitiric oxide (NO) as well as prostaglandins (PGs). In this study, we examined the effects of various inhibitors of cyclooxygenase (COX) or NO synthase (NOS) on the acid-induced HCO3− secretion in rats and determined the enzyme isoforms responsible for this response. A proximal duodenal loop was perfused with saline under urethane anesthesia, and the HCO3− secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. Mucosal acidification was performed by exposing the loop to 10 mM HCl for 10 min. Indomethacin, SC-560 (a selective COX-1 inhibitor) and rofecoxib (a selective COX-2 inhibitor) were given intraduodenally 1 hr before exposure to 10 mM HCl, while NG-nitro-l-arginine methyl ester (l-NAME: a nonselective NOS inhibitor) and aminoguanidine (a relatively selective inhibitor of iNOS) were given subcutaneously 3 hr before the acidification. The mucosal acidification increased the HCO3− secretion, with a rise in mucosal PGE2 content and luminal release of NO. The HCO3− secretory and PGE2 biosynthetic responses were significantly inhibited by indomethacin and SC-560, while rofecoxib had no effect on these responses. On the other hand, l-NAME, but not aminoguanidine, attenuated NO release following the acidification, resulting in inhibition of the acid-induced HCO3− secretion in a l-arginine-sensitive manner. Neither COX-2 nor iNOS mRNAs were observed in the mucosa before and 1 hr after acidification, while the gene expression of COX-1 and nNOS was constitutively detected in the mucosa and appeared to be slightly up-regulated after the acid stimulation. These results suggest that COX-1 and cNOS play as the respective key enzyme responsible for producing PG and NO following the duodenal acidification, both of which are involved in the mechanism for the acid-induced HCO3− secretion in the duodenum.

Duodenal HCO3- secretion increases in response to luminal acid, mediated by endogenous nitric oxide (NO) as well as prostaglandins (PGs). In this study, we examined the effects of various inhibitors of cyclooxygenase (COX) or NO synthase (NOS) on the acid-induced HCO3- secretion in rats and determined the enzyme isoforms responsible for this response. A proximal duodenal loop was perfused with saline under urethane anesthesia, and the HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. Mucosal acidification was performed by exposing the loop to 10 mM HCl for 10 min. Indomethacin, SC-560 (a selective COX-1 inhibitor) and rofecoxib (a selective COX-2 inhibitor) were given intraduodenally 1 hr before exposure to 10 mM HCl, while N(G)-nitro-L-arginine methyl ester (L-NAME: a nonselective NOS inhibitor) and aminoguanidine (a relatively selective inhibitor of iNOS) were given subcutaneously 3 hr before the acidification. The mucosal acidification increased the HCO3- secretion, with a rise in mucosal PGE2 content and luminal release of NO. The HCO3- secretory and PGE2 biosynthetic responses were significantly inhibited by indomethacin and SC-560, while rofecoxib had no effect on these responses. On the other hand, L-NAME, but not aminoguanidine, attenuated NO release following the acidification, resulting in inhibition of the acid-induced HCO3- secretion in a L-arginine-sensitive manner. Neither COX-2 nor iNOS mRNAs were observed in the mucosa before and 1 hr after acidification, while the gene expression of COX-1 and nNOS was constitutively detected in the mucosa and appeared to be slightly up-regulated after the acid stimulation. These results suggest that COX-1 and cNOS play as the respective key enzyme responsible for producing PG and NO following the duodenal acidification, both of which are involved in the mechanism for the acid-induced HCO3- secretion in the duodenum.