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

我们研究了前列腺素(PGs)和EP受体在辣椒素对大鼠和小鼠的胃保护作用中的作用，(2)与粘膜酸化相比，VR1在大鼠十二指肠对HCO3分泌反应中的作用；(3)VR1在胃粘膜上皮细胞的外周表达及其在细胞保护中的作用，得到以下结果：1.PGE_2和辣椒素均能显著抑制HCl/乙醇诱导的胃损伤。EP1拮抗剂AE-829可拮抗PGE_2的作用，而辣椒素的作用可被消炎痛和感觉去传入减弱，但不能被AE-829所拮抗。辣椒素以吲哚美辛抑制的方式对盐酸/乙醇诱导的WT(+/+)小鼠的胃损伤起到保护作用，在EP1(-/-)和EP3(-/-)小鼠中观察到类似的作用，但在缺乏…的动物中没有观察到这种作用更多的IP受体。因此，辣椒素表现出胃细胞保护作用，主要是通过刺激感觉神经元，而这一作用是由内源性PGs通过EP2/IP受体促进的，可能使感觉神经元对辣椒素敏感。2.辣椒素和酸都能引起十二指肠HCO3~-分泌增加，依赖于辣椒素敏感的感觉神经元，并由一氧化氮和PGs介导，但它们的作用方式不同，对Ru红或辣椒碱的敏感性不同。尽管鲁米那对十二指肠HCO3~-的分泌有一定的调节作用，但这种作用不可能是H~(++)与Ru红或卡萨西平敏感部位VR1.3的相互作用所致。在RGM-1以及大鼠的胃和脊髓中均检测到VR1蛋白和mRNA的表达。辣椒素可防止乙醇或酸引起的细胞损伤，这种作用可被辣椒碱或钌红共同加入而取消。推测VR1在胃粘膜上皮细胞中呈外周表达，具有细胞保护作用。较少

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