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Effect of melatonin on chloride secretion by human colonic T84 cells.

机译:褪黑激素对人结肠T84细胞氯化物分泌的影响。

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The effect of melatonin on human colonic T84 cells was studied using the short-circuit current (I(SC)) technique. Basolateral, as well as apical, addition of melatonin stimulated I(SC) in a concentration-dependent manner (EC50 at about 100 microM). The I(SC) response to melatonin was nearly abolished when external Cl- was removed. The increase in I(SC) was also blocked by apical addition of two Cl- channel blockers, 4,4'-diisothiocyanatostibene-2,2'-disulfonic acid (DIDS) and diphenylamine-2-carboxylic acid (DPC), indicating that melatonin stimulated Cl- secretion. The effect of different melatonin analogs was compared and the order of potency appeared to be 2-iodomelatonin > melatonin > 6-hydroxymelatonin, indicating the involvement of melatonin receptors. However, inhibitors for Gi-protein, adenylate cyclase or phospholipase C were found to be ineffective in inhibiting the melatonin-induced I(SC). Pretreatment of the cells with melatonin was also found to exert little effect on subsequent forskolin- or VIP-induced I(SC), further excluding its interaction with adenylate cyclase. Our data suggest that melatonin may play a role in regulating colonic Cl- secretion via melatonin receptors; however, the signal transduction pathway(s) involved remains to be elucidated.
机译:使用短路电流(I(SC))技术研究了褪黑激素对人结肠T84细胞的影响。褪黑激素的基础外侧和顶端均以浓度依赖性方式(约50 microM的EC50)添加褪黑激素刺激的I(SC)。去除外部Cl-后,对褪黑激素的I(SC)反应几乎消失了。 I(SC)的增加也被顶端添加了两个Cl通道阻滞剂,4,4'-二异硫氰基苯乙烯2-2,2'-二磺酸(DIDS)和二苯胺-2-羧酸(DPC)所阻止,这表明褪黑激素刺激Cl-分泌。比较了不同褪黑激素类似物的作用,效力的顺序似乎是2-碘褪黑激素>褪黑激素> 6-羟基褪黑激素,表明褪黑激素受体的参与。但是,发现Gi蛋白,腺苷酸环化酶或磷脂酶C的抑制剂在抑制褪黑激素诱导的I(SC)方面无效。还发现用褪黑激素预处理细胞对随后的福司可林或VIP诱导的I(SC)几乎没有影响,进一步排除了其与腺苷酸环化酶的相互作用。我们的数据表明,褪黑激素可能在通过褪黑激素受体调节结肠Cl-分泌中发挥作用。然而,所涉及的信号转导途径尚待阐明。

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