MECHANISM OF GASTRIC ALKALINE RESPONSE IN THE STOMACH AFTER DAMAGE - ROLES OF NITRIC-OXIDE AND PROSTAGLANDINS

被引:39
作者
TAKEUCHI, K
OKABE, S
机构
[1] From the Department of Applied Pharmacology, Kyoto Pharmaceutical University, Kyoto, 607, Misasagi, Yamashina
关键词
HYPERTONIC NACL; GASTRIC ALKALINE SECRETION; PROSTAGLANDIN; NITRIC OXIDE; INDOMETHACIN; N-G-NITRO-L-ARGININE METHYL ESTER;
D O I
10.1007/BF02064993
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The gastric mucosa responds to hypertonic NaCl by significantly decreasing acid secretion. We examined the role nitric oxide (NO) in this phenomenon in comparison with endogenous prostaglandins (PGs). A rat stomach was mounted in an ex vivo chamber, perfused with saline, and the potential difference (PD), pH, and acid/alkaline responses were measured before and after the application of hypertonic NaCl (1 mol/liter) with or without pretreatment with N-G-nitro-L-arginine methyl ester (L-NAME; an inhibitor of NO biosynthesis) or indomethacin (a cyclooxygenase inhibitor). NaCl at 1 M caused a PD reduction, a decrease in acid secretion and an increase in luminal HCO3-. Prior administration of L-NAME (5 mg/kg, intravenously) as well as indomethacin (5 mg/kg, subcutaneously) did not affect PD and HCO3- responses, but significantly attenuated the inhibitory effect of 1 M NaCl on acid secretion, although the effect of L-NAME was more potent when compared to indomethacin. This effect of L-NAME was antagonized by the simultaneous administration of L-arginine but not by D-arginine (200 mg/kg, intravenously), whereas the effect of indomethacin was completely reversed by PGE(2) (100 mu g/kg, intravenously). The histamine-stimulated acid secretion in the normal stomach was significantly decreased by nitroprusside (the exogenous NO donor; 4 mg/kg, intravenously) and PGE(2), but not by either L-NAME or indomethacin. These results suggest that in addition to PGs, NO is involved in the mechanism of the gastric alkaline response after damage with 1 M NaCl. Irritation of the gastric mucosa by hypertonic NaCl may release endogenous NO and PGs, both of which in turn inhibit acid secretion and unmask luminal alkalinization due to HCO3- flux in the damaged portion.
引用
收藏
页码:865 / 871
页数:7
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