Kato S, Abe Y, Konishi M, Kuroda N, Takeuchi K
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan.
J Clin Gastroenterol. 1997;25 Suppl 1:S48-55. doi: 10.1097/00004836-199700001-00009.
The mechanism of gastric mucosal hyperemic response during pentagastrin-induced acid secretion was investigated in anesthetized rats in relation to prostaglandins (PGs), nitric oxide (NO), and sensory neurons. A rat stomach was mounted in an ex vivo chamber and perfused with saline or glycine (200 mM), and the mucosal blood flow (GMBF), determined by laser Doppler flowmetry, and acid secretion was measured simultaneously. Intravenous infusion with a submaximal dose of pentagastrin (60 micrograms/kg/h) caused a significant increase in GMBF as well as acid secretion. Such GMBF responses were totally attenuated when acid secretion was inhibited by omeprazole and cimetidine or when the luminal H+ was buffered by mucosal perfusion with glycine (200 mM). Tripelennamine, an H1 antagonist, did not have any affect on acid secretory and GMBF responses to pentagastrin. On the other hand, prior administration of NG-nitro-L-arginine methyl ester (L-NAME), the NO synthase inhibitor, significantly mitigated the increase of GMBF induced by pentagastrin without any influence on acid secretion, and this effect was antagonized by simultaneous administration of L-arginine. The gastric hyperemic response to pentagastrin was also significantly mitigated by indomethacin or sensory deafferentation after capsaicin pretreatment, with no effect on acid secretion, and was totally inhibited by combined treatments with indomethacin plus L-NAME in addition to sensory deafferentation. Pentagastrin infusion for 8 h did not by itself cause macroscopic damage in the stomach, but additional treatments with L-NAME and indomethacin plus sensory deafferentation provoked severe lesions in the gastric mucosa. These results suggest that the gastric hyperemic response to pentagastrin (submaximal dose) is totally dependent on H+ and that this process is mediated by endogenous NO and PGs as well as by capsaicin-sensitive sensory neurons and plays a pivotal role in maintaining mucosal integrity during acid secretion.
在麻醉大鼠中，研究了五肽胃泌素诱导胃酸分泌期间胃黏膜充血反应的机制，该机制与前列腺素（PGs）、一氧化氮（NO）和感觉神经元有关。将大鼠胃置于离体腔室中，用生理盐水或甘氨酸（200 mM）灌注，通过激光多普勒血流仪测定黏膜血流量（GMBF），并同时测量胃酸分泌。静脉输注次最大剂量的五肽胃泌素（60微克/千克/小时）可导致GMBF以及胃酸分泌显著增加。当奥美拉唑和西咪替丁抑制胃酸分泌或通过用甘氨酸（200 mM）进行黏膜灌注缓冲管腔内H+时，这种GMBF反应完全减弱。H1拮抗剂曲吡那敏对五肽胃泌素引起的胃酸分泌和GMBF反应没有任何影响。另一方面，预先给予NO合酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）可显著减轻五肽胃泌素诱导的GMBF增加，而对胃酸分泌没有任何影响，并且这种作用可被同时给予L-精氨酸所拮抗。辣椒素预处理后进行消炎痛或感觉神经去传入处理，对五肽胃泌素的胃充血反应也有显著减轻作用，对胃酸分泌无影响，除感觉神经去传入外，消炎痛加L-NAME联合处理可完全抑制该反应。输注五肽胃泌素8小时本身不会引起胃的宏观损伤，但L-NAME、消炎痛加感觉神经去传入的额外处理会引发胃黏膜严重损伤。这些结果表明，对五肽胃泌素（次最大剂量）的胃充血反应完全依赖于H+，并且该过程由内源性NO、PGs以及辣椒素敏感的感觉神经元介导，在胃酸分泌期间维持黏膜完整性方面起关键作用。
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