Distribution of vanilloid receptors (VR1) in gastrointestinal tract and their role in mucosal protection mediated by capsaicin-sensitive afferent neurons

我们研究了辣椒素（Capsaicin）对大鼠和小鼠胃粘膜的保护作用中辣椒素受体（PGs）和EP受体的作用;辣椒素受体1（VR 1）在大鼠胃粘膜HCO_3分泌反应中的作用，并与粘膜酸化反应进行了比较;结果表明：（1）PGE_2和辣椒素对盐酸/乙醇诱导的胃粘膜损伤有明显的抑制作用。PGE_2的作用可被EP_1拮抗剂AE-829所拮抗，而辣椒素的作用可被消炎痛和感觉传入阻滞所减轻，但AE-829不起作用。辣椒素以吲哚美辛可耐受的方式对WT（+/+）小鼠中HCl/乙醇诱导的胃损伤提供保护作用，并且在EP 1（-/-）和EP 3（-/-）小鼠中类似地观察到该作用，但在缺乏吲哚美辛的动物中没有观察到。 关于我们 IP受体。辣椒素对胃细胞具有保护作用，其机制主要是通过刺激感觉神经元，而内源性PGs通过EP 2/IP受体促进了这一作用，可能是辣椒素使感觉神经元对辣椒素敏感。2.辣椒素和辣椒酸均通过辣椒素敏感的感觉神经元，并通过一氧化氮和PGs介导，引起十二指肠HCO_3^-分泌的增加。然而，它们的作用模式在钌红或辣椒碱敏感性方面不同。虽然腔H^+对十二指肠HCO_3^-的分泌有调节作用，但这种调节作用不可能是由于H^+与VR1.3的钌红或辣椒碱敏感位点相互作用所致。辣椒素可防止乙醇或酸引起的细胞损伤，这种作用可被辣椒平或钌红的共同加入所消除。据推测，VR 1在胃粘膜上皮细胞的外周表达，并发挥细胞保护作用。少

We investigated (1)the role prostaglandins (PGs) and EP receptors play in facilitating the gastroprotective action of capsaicin against HCl/ethanol in rats and mice, (2)the role of VR1 in the HCO_3 secretory response to capsaicin in rat duodenums, in comparison with that induced by mucosal acidification, and (3)the peripheral expression of VR1, in gastric mucosal epithelial cells as well as the role of the receptor in cellular protection, and the following results were obtained ;1.Gastric lesions induced by HCl/ethanol were significantly inhibited by PGE_2 as well as capsaicin. The effect of PGE_2 was antagonized by AE-829 (EP1 antagonist), while the capsaicin action was mitigated by indomethacin as well as sensory deafferentation but not by AE-829. Capsaicin provided a protective action against HCl/ethanol-induced gastric lesions in WT (+/+) mice in an indomethacin-inhibitable manner, and this action was similarly observed in EP1 (-/-) and EP3 (-/-) mice but not in the animals lacking … More IP receptors. Thus, capsaicin exhibits gastric cytoprotection, essentially by stimulating sensory neurons, and this action is facilitated by endogenous PGs through EP2/IP receptors, probably sensitizing the sensory neurons to capsaicin.2.Both capsaicin and acid cause an increase in duodenal HCO_3^-secretion depending on capsaicin-sensitive sensory neuron and mediated by nitric oxide and PGs, yet the mode of their action differs in terms of the ruthenium red-or capsazepine-sensitivity. Although luminal H^+ plays a modulatory role in duodenal HCO_3^-secretion, it is unlikely that the action results from the interaction of H^+ with the ruthenium red-or capsazepine-sensitive site of VR1.3.The distinct expression of VR1 protein and mRNA was detected in RGM-1 as well as the rat stomach and spinal cord. Capsaicin prevented the cell damage induced by ethanol or acid, the effect being abolished by co-addition of capsazepine or ruthenium red. It is assumed that VR1 is expressed peripherally in gastric mucosal epithelial cells and plays a cellular protective role. Less