Effect of caffeine on mucus secretion and agonist-dependent Ca2+ mobilization in human gastric mucus secreting cells.

Effect of caffeine on mucus secretion and agonist-dependent Ca2+ mobilization in human gastric mucus secreting cells.
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咖啡因对人胃粘液分泌细胞中粘液分泌和激动剂依赖性 Ca2+ 动员的影响。

DOI:
10.1016/s0167-4889(96)00177-2
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发表时间:
1997
期刊:
Biochimica et Biophysica Acta
影响因子:
--
通讯作者:
M. Omata
M. Omata
中科院分区:
--
文献类型:
--
作者:
E. Hamada;T. Nakajima;Y. Hata;H. Hazama;K. Iwasawa;M. Takahashi;S. Ota;M. Omata

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已知咖啡因会刺激胃酸分泌,但是咖啡因对胃粘液分泌的影响尚未阐明。为了阐明咖啡因对胃粘蛋白产生细胞的作用及其潜在机制,我们在人胃粘蛋白分泌细胞(JR-I细胞)中检查了咖啡因对粘液糖蛋白分泌和激动剂诱导的[Ca2+]固定化的影响。采用Indo-1和全细胞电压钳技术测量[Ca2+]。通过[3H]葡萄糖胺的释放来评估粘液糖蛋白分泌。咖啡因本身不能增加[Ca2+]并影响膜电流,但它剂量依赖性地抑制激动剂(乙酰胆碱(ACh)或组胺)诱导的[Ca2+]虹膜,从而抑制激动剂诱发的Ca2+依赖性K+电流(IK.Ca)的激活。咖啡因的作用是可逆的,半数抑制浓度约为0.5 mM。但是,咖啡因不会抑制 A23187 或肌醇三磷酸 (IP3) 诱导的 [Ca2+]iris 和 IK.Ca 激活。茶碱或 3-异丁基-1-甲基-黄嘌呤 (IBMX) 不能模拟咖啡因的效果。咖啡因不能刺激粘液分泌,但它显着减少乙酰胆碱诱导的粘液分泌。这些结果表明,咖啡因选择性抑制人胃上皮细胞中激动剂介导的[Ca2+]虹膜,可能是通过阻断受体-IP3信号通路,从而影响粘蛋白分泌。 © 1997 Elsevier Science B.V. 保留所有权利。
Caffeine is known to stimulate gastric acid secretion, but, the effects of caffeine on gastric mucus secretion have not been clarified. To elucidate the action of caffeine on gastric mucin-producing cells and its underlying mechanism, the effects of caffeine on mucus glycoprotein secretion and agonist-induced [Ca2+]imobilization were examined in human gastric mucin secreting cells (JR-I cells). The measurement of [Ca2+]iusing Indo-1 and the whole cell voltage clamp technique were applied. Mucus glycoprotein secretion was assessed by release of [3H]glucosamine. Caffeine by itself failed to increase [Ca2+]iand affect membrane currents, while it dose-dependently inhibited agonist (acetylcholine (ACh) or histamine)-induced [Ca2+]irise, resulting in inhibiting activation of Ca2+-dependent K+current (IK.Ca) evoked by agonists. The effect of caffeine was reversible, and the half maximal inhibitory concentration was about 0.5 mM. But, caffeine did not suppress [Ca2+]irise and activation of IK.Cainduced by A23187 or inositol trisphosphate (IP3). Theophylline or 3-isobutyl-1-methyl-xanthine (IBMX) did not mimic the effect of caffeine. Caffeine failed to stimulate mucus secretion, while it significantly decreased ACh-induced mucus secretion. These results indicate that caffeine selectively inhibits agonist-mediated [Ca2+]irise in human gastric epithelial cells, probably through the blockade of receptor-IP3signaling pathway, which may affect the mucin secretion. © 1997 Elsevier Science B.V. All rights reserved.