Gastro-protective action of lafutidine mediated by capsaicin-sensitive afferent neurons without interaction with TRPV1 and involvement of endogenous prostaglandins

瞄准：Lafutidine，一个组织安 H2 受体对手，展览胃保护的行动由 capsaicin 敏感的传入神经元(CSN ) 调停了。我们比较了在 lafutidine 和辣椒辣素之间的效果，关于和内长的前列腺素(PG ) 的相互作用，氮的氧化物(没有) 并且传入神经元，包括短暂受体潜力 vanilloid 子类型 1 (TRPV1 ) 。方法：男 SD 老鼠和 C57BL/6 老鼠，野类型并且 prostacyclin IP 受体大美人动物，在禁食的 18 h 以后被使用。胃的损害被 HCl/ethanol 的 po 管理导致(60% 在 150 mmol/L HCl ) 在为老鼠的 1 mL 或为老鼠的 0.3 mL 的体积。结果：lafutidine 和辣椒辣素(1-10 mg/kg， po ) 对在老鼠和老鼠的 HCl/ethanol 的负担得起的剂量依赖者保护。效果被两个稀释有 N (G)-nitro-L-arginine 甲基酉旨的 CSN 和预告的处理的脱离，然而，仅仅辣椒辣素的效果被 capsazepine， TRPV1 对手，以及消炎痛的优先的管理减轻。Lafutidine 在 IP 受体大美人老鼠保护了胃免于 HCl/ethanol，类似于野类型的动物，当辣椒辣素没能在缺乏 IP 受体的动物负担得起保护时。任何一个这些代理人都没在老鼠胃影响粘膜 PGE2 或 6-keto PGF (1alpha ) 内容。辣椒辣素唤起了增加在[Ca2+] 在老鼠 TRPV1-transfected HEK293 房间的 i 当时 lafutidine 不。结论：这些结果建议尽管 lafutidine 和辣椒辣素展出，胃保护的行动由 CSN 调停了，他们的效果的模式在内长的 PGs/IP 受体和 TRPV1 上关于相关性不同。lafutidine 在除 TRPV1 以外的还未辩别出的地点与 CSN 交往，这被假定。

AIM： Lafutidine, a histamine H2 receptor antagonist, exhibits gastro-protective action mediated by capsaicinsensitive afferent neurons （CSN）. We compared the effect between lafutidine and capsaicin, with respect to the interaction with endogenous prostaglandins （PG）, nitric oxide （NO） and the afferent neurons, including transient receptor potential vanilloid subtype 1 （TRPV1）. METHODS： Male SD rats and C57BL/6 mice, both wildtype and prostacyclin IP receptor knockout animals, were used after 18 h of fasting. Gastric lesions were induced by the po administration of HCl/ethanol （60% in 150 mmol/L HCl） in a volume of 1 mL for rats or 0.3 mL for mice. RESULTS： Both lafutidine and capsaicin （1-10 mg/kg, po） afforded dose-dependent protection against HCI/ ethanol in rats and mice. The effects were attenuated by both the ablation of CSN and pretreatment with NG-nitro- L-arginine methyl ester, yet only the effect of capsaicin was mitigated by prior administration of capsazepine, the TRPV1 antagonist, as well as indomethacin. Lafutidine protected the stomach against HCl/ethanol in IP receptor knockout mice, similar to wild-type animals, while capsaicin failed to afford protection in the animals lacking IP receptors. Neither of these agents affected the mucosal PGE2 or 6-keto PGF1α contents in rat stomachs. Capsaicin evoked an increase in [Ca^2＋]i in rat TRPV1-transfected HEK293 cells while lafutidine did not. CONCLUSION： These results suggest that although both lafutidine and capsaicin exhibit gastro-protective action mediated by CSN, the mode of their effects differs regarding the dependency on endogenous PGs/IP receptors and TRPV1. It is assumed that lafutidine interacts with CSN at yet unidentified sites other than TRPV1.