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TRP channels as a newly emerging non-voltage-gated CA2+ entry channel superfamily.

机译:TRP通道是一种新兴的非电压门控CA2 +进入通道超家族。

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It has long been known that many chemical and physical stimuli imposed on the cell from its exterior environments elicit a long-lasting Ca2+ influx through yet poorly elucidated transmembrane pathways distinct from voltage-gated and fast ligand-gated Ca2+ entry channels, thereby activating and modulating a variety of cellular functions. Recent progress in molecularly identifying these pathways, initiated from the discovery of Drosophila's visual transduction mutants transient receptor potential (TRP) proteins, has begun to reveal the presence of an enormous superfamily of non-voltage-gated Ca2+ channels. The mammalian members of TRP superfamily are (except for two members) Ca2+-permeable non-selective cation channels which are constitutively active or gated by a multitude of physicochemical stimuli such as receptor stimulation, phospholipids, oxidants, pheromones, cell volume change/shear stress, exogenous compounds affecting sensations, and changes in ambient temperature, acidity and osmolarity and cellular metabolic status. Owing to these diversities in activation and their broad distribution from brain to peripheral organs and tissues, TRP channels are now thought to be involved in divergent physiological functions including; pain and taste transductions; thermo- and mechano-sensations; regulation of mineral absorption/reabsorption; blood pressure, gut motility and airway responsiveness; cell proliferation/death, some of which seem tightly associated with specific genetic disorders. These features will render TRP channels the attractive novel molecular targets for future drug therapy. This paper briefly overviews the current knowledge available for these channels with a main interest in their possible linkage with in vivo function.
机译:长期以来,人们已经知道,从细胞外部环境对细胞施加的许多化学和物理刺激会通过尚未充分阐明的跨膜途径(不同于电压门控和快速配体门控的Ca2 +进入通道)引发持久的Ca2 +流入,从而激活和调节多种细胞功能。从果蝇视觉转导突变体的瞬时受体电位(TRP)蛋白的发现开始,分子鉴定这些途径的最新进展开始揭示了巨大的非电压门控Ca2 +通道超家族的存在。 TRP超家族的哺乳动物成员是(两个成员除外)可渗透Ca2 +的非选择性阳离子通道,这些通道具有组成性活性或被多种物理化学刺激(如受体刺激,磷脂,氧化剂,信息素,细胞体积变化/剪切应力)控制,影响感觉,环境温度,酸度,渗透压和细胞代谢状态变化的外源性化合物。由于激活的多样性以及它们从大脑到周围器官和组织的广泛分布,现在认为TRP通道参与了多种生理功能,包括:疼痛和味觉转换;热感和机械感;调节矿物质吸收/再吸收;血压,肠动力和气道反应性;细胞增殖/死亡,其中一些似乎与特定的遗传疾病紧密相关。这些功能将使TRP通道成为未来药物治疗的有吸引力的新型分子靶标。本文简要概述了这些通道的可用现有知识,主要关注它们与体内功能的可能联系。

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