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Pharmacological characterisation of voltage-dependent Ca2+ channels in isolated ganglia from the myenteric plexus.

机译:肌间神经丛中离体神经节中电压依赖性Ca2 +通道的药理学表征。

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摘要

Voltage-dependent Ca2+ channels of fura-2-loaded ganglionic cells from the myenteric plexus of newborn rats were pharmacologically characterised. In contrast to completely dissociated myenteric cells, intact ganglia showed a stronger loading with the Ca2+-sensitive dye and a reproducible stimulation of the fura-2 signal by the cholinergic agonist, carbachol. A depolarisation-induced increase in the intracellular Ca2+ concentration ([Ca2+]i) was induced by superfusion with 35 mmol l(-1) KCl. This increase in [Ca2+]i was sensitive to Ni2+ and Co2+ as well as omega-conotoxin MVIIA, omega-agatoxin IVA, and SNX-482. The strongest inhibition was achieved by nifedipine (5 x 10(-7) mol l(-1)) and omega-conotoxin GVIA (4.3 x 10(-7) mol l(-1)). These two blockers also inhibited the [Ca2+]i increase evoked by nicotinic receptor stimulation. Consequently, isolated myenteric ganglia in culture express different types of voltage-dependent Ca2+ channels, from which the L- and the N-type seem to be the most important.When exposed to mediators of inflammation such as tumor necrosis factor-alpha (TNF-alpha) or different prostaglandins, no pronounced alterations in the fura-2 ratio were observed suggesting that changes in the Ca2+-signalling are not centrally involved in the response of enteric ganglionic cells to these paracrine substances.
机译:新生鼠的肌间神经丛中呋喃2加载的神经节细胞的电压依赖性Ca2 +通道具有药理学特性。与完全解离的肌层细胞相反,完整的神经节显示对Ca2 +敏感的染料具有更强的负载能力,并且胆碱能激动剂卡巴胆碱对fura-2信号具有可再现的刺激。通过与35 mmol l(-1)KCl的超融合诱导去极化诱导的细胞内Ca2 +浓度([Ca2 +] i)的增加。 [Ca2 +] i的增加对Ni2 +和Co2 +以及ω-芋螺毒素MVIIA,ω-毒素毒素IVA和SNX-482敏感。硝苯地平(5 x 10(-7)mol l(-1))和ω-芋螺毒素GVIA(4.3 x 10(-7)mol l(-1))实现了最强的抑制作用。这两种阻滞剂也抑制了烟碱样受体刺激引起的[Ca2 +] i增加。因此,培养物中分离的肌间神经节表达不同类型的电压依赖性Ca2 +通道,其中L型和N型似乎是最重要的。当暴露于炎症介质(如肿瘤坏死因子-α(TNF- α)或不同的前列腺素,未观察到fura-2比率的明显变化,这表明Ca2 +信号转导的变化并不集中参与肠神经节细胞对这些旁分泌物质的反应。

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