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渗透和热敏控制大细胞神经分泌神经元——TRPV1 N 端变异体的作用。

Osmotic and thermal control of magnocellular neurosecretory neurons--role of an N-terminal variant of trpv1.

机构信息

Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal, QC, Canada.

出版信息

Eur J Neurosci. 2010 Dec;32(12):2022-30. doi: 10.1111/j.1460-9568.2010.07512.x.

DOI:10.1111/j.1460-9568.2010.07512.x
PMID:21143657
Abstract

The release of vasopressin (antidiuretic hormone) plays a key role in the osmoregulatory response of mammals to changes in salt or water intake and in the rate of water loss through evaporation during thermoregulatory cooling. Previous work has shown that the hypothalamus encloses the sensory elements that modulate vasopressin release during systemic changes in fluid osmolality or body temperature. These responses depend in part on a synaptic regulation of vasopressin neurons by afferent inputs arising from osmosensory and thermosensory neurons in the preoptic area. However, recent studies in rats and mice have shown that vasopressin neurons in the supraoptic nucleus also display intrinsic osmosensory and thermosensory properties. Isolated vasopressin neurons exposed to increases in perfusate temperature or osmolality generate increases in non-selective cation channel activity that cause membrane depolarization and increase neuronal excitability. These channels are calcium-permeable and can be blocked by ruthenium red. Moreover, intrinsic responses to osmotic and thermal stimuli are absent in magnocellular neurosecretory cells isolated from mice lacking the transient receptor potential vanilloid-1 (trpv1) gene, which encodes the capsaicin receptor. Immunostaining of vasopressin-releasing neurons with anti-TRPV1 antibodies reveals the presence of amino acids present in the carboxy terminus of the protein, but not those lying in the amino terminal domain. Thus, magnocellular neurosecretory neurons appear to express an N-terminal variant of trpv1 which lacks sensitivity to capsaicin, but which enables osmosensing and thermosensing.

摘要

血管升压素(抗利尿激素)的释放在哺乳动物对盐或水摄入变化以及在热调节冷却过程中通过蒸发丧失水分的速率的渗透压调节反应中起着关键作用。先前的工作表明,下丘脑包含调节血管升压素释放的感觉元件,这些感觉元件在全身液体渗透压或体温变化期间起作用。这些反应部分取决于来自视前区的渗透压和热敏神经元的传入输入对血管升压素神经元的突触调节。然而,最近在大鼠和小鼠中的研究表明,神经垂体中的血管升压素神经元也表现出内在的渗透压和热敏特性。暴露于灌流液温度或渗透压增加的分离血管升压素神经元会引起非选择性阳离子通道活性增加,导致膜去极化并增加神经元兴奋性。这些通道是钙渗透性的,可以被钌红阻断。此外,在缺乏编码辣椒素受体的瞬时受体电位香草素 1 (TRPV1) 基因的小鼠中分离出的大细胞神经分泌细胞中,不存在对渗透压和热刺激的内在反应。用抗 TRPV1 抗体对血管升压素释放神经元进行免疫染色显示存在于蛋白质羧基末端的氨基酸,但不存在位于氨基末端结构域中的氨基酸。因此,大细胞神经分泌神经元似乎表达 TRPV1 的 N 末端变体,该变体对辣椒素不敏感,但能够进行渗透压和热敏感应。

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