Mascolo N, Gaginella T S, Izzo A A, Di Carlo G, Capasso F
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.
Eur J Pharmacol. 1994 Oct 13;264(1):21-6. doi: 10.1016/0014-2999(94)90630-0.
Bile salt-induced diarrhoea, net water and electrolyte secretion, gastrointestinal transit and nitric oxide (NO) synthase activity were studied in rats. NG-Nitro-L-arginine methyl ester (2.5-25 mg/kg i.p.), an inhibitor of NO synthase, and dexamethasone (0.03-0.3 mg/kg i.p.), an inhibitor of the inducible isoform of NO synthase, antagonized the diarrhoeal response. The NO precursor, L-arginine and isosorbide-5-mononitrate (an NO donor), reversed the inhibitory effect of NG-nitro-L-arginine methyl ester. The bile salt-stimulated fluid secretion, transit through the gut and NO synthase all were inhibited by NG-nitro-L-arginine methyl ester (but not NG-nitro-D-arginine methyl ester). NO synthase activity also was inhibited by dexamethasone. The results are consistent with bile salt induction of epithelial cell injury and concomitant synthesis of NO, mainly through activation of the inducible form of the enzyme. We believe that in this study NO is a mediator of intestinal secretion and motility changes that enhance transit of luminal contents through the gut, resulting in diarrhoea.
在大鼠中研究了胆盐诱导的腹泻、净水分和电解质分泌、胃肠转运及一氧化氮（NO）合酶活性。NO合酶抑制剂NG-硝基-L-精氨酸甲酯（2.5 - 25毫克/千克，腹腔注射）和诱导型NO合酶抑制剂地塞米松（0.03 - 0.3毫克/千克，腹腔注射）可拮抗腹泻反应。NO前体L-精氨酸和5-单硝酸异山梨酯（一种NO供体）可逆转NG-硝基-L-精氨酸甲酯的抑制作用。NG-硝基-L-精氨酸甲酯（而非NG-硝基-D-精氨酸甲酯）可抑制胆盐刺激的液体分泌、肠道转运及NO合酶。地塞米松也可抑制NO合酶活性。结果表明，胆盐主要通过激活诱导型酶诱导上皮细胞损伤并伴随NO合成。我们认为，在本研究中，NO是肠道分泌和运动变化的介质，可增强肠腔内物质通过肠道的转运，导致腹泻。
