| Co-Investigator(Kenkyū-buntansha) |
TANAKA Akiko Kyoto Pharmaceutical University, Pharmacology and Experimental Therapeutics, Research Associate, 薬学部・薬物治療学教室, 助手 (30329940)
KATO Shinichi Kyoto Pharmaceutical University, Pharmacology and Experimental Therapeutics, Assistant Professor, 薬学部・薬物治療学教室, 講師 (90281500)
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| Research Abstract |
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
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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
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