Niki S, Rokutan K, Nakamura K, Ogihara S, Kutsumi H, Saitoh T, Aoike A, Kawai K
Department of Preventive Medicine, Kyoto Prefectural University of Medicine.
Nihon Shokakibyo Gakkai Zasshi. 1992 Aug;89(8):1484-90.
Treatment of isolated parietal cells from guinea pig gastric mucosa with ethanol caused a rapid increase in [Ca2+]i and concomitant decrease in the capacity for carbachol-stimulated acid secretion in a dose dependent manner. Carbachol rapidly increased the [Ca2+]i from trimethoxybenzoic acid 8-(diethylamino)-octyl ester sensitive intracellular pool. In contrast, the increase with ethanol was through La3+ sensitive Ca2+ channel from external source, which suppressed the Ca2+ response subsequently stimulated with carbachol. Pretreatment of the cells with EGTA or La3+ completely prevented the elevation of [Ca2+]i with ethanol and preserved the Ca2+ response to carbachol. These findings indicate that ethanol-induced elevation of [Ca2+]i may desensitize the stimulation of carbachol. Furthermore, treatment of the parietal cells with ethanol increased the activity of protein kinase C in both cytosolic and membrane fractions of the cells. Activation of protein kinase C with phorbol diester suppressed the capacity for acid secretion. These results suggest that ethanol may inhibit the carbachol-stimulated acid secretion through the desensitization of Ca2+ response and the activation of protein kinase C.
用乙醇处理豚鼠胃黏膜分离的壁细胞，会导致细胞内钙离子浓度（[Ca2+]i）迅速升高，并伴随卡巴胆碱刺激的酸分泌能力呈剂量依赖性下降。卡巴胆碱能迅速使[Ca2+]i从三甲氧基苯甲酸8 - （二乙氨基）辛酯敏感的细胞内储存库中升高。相比之下，乙醇引起的升高是通过对镧离子（La3+）敏感的细胞外钙离子通道，这随后抑制了卡巴胆碱刺激产生的钙离子反应。用乙二醇双（2 - 氨基乙基醚）四乙酸（EGTA）或La3+预处理细胞可完全阻止乙醇引起的[Ca2+]i升高，并保留对卡巴胆碱的钙离子反应。这些发现表明，乙醇诱导的[Ca2+]i升高可能使卡巴胆碱的刺激作用脱敏。此外，用乙醇处理壁细胞会增加细胞胞质和膜部分中蛋白激酶C的活性。用佛波酯激活蛋白激酶C会抑制酸分泌能力。这些结果表明，乙醇可能通过使钙离子反应脱敏和激活蛋白激酶C来抑制卡巴胆碱刺激的酸分泌。
