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Three-dimensional analysis and molecular mechanism of the peptidergic innervation in the arterial chemoreceptor organ

动脉化学感受器肽能神经支配的三维分析及分子机制

基本信息

批准号：
09670022
负责人：
KUSAKABE Tatsumi
金额：
$ 1.86万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

The carotid bodies, which are the primary sensory organs for sensing changes in arterial blood gases and hydrogen ion concentration, were enlarged in the rat exposed to chronic isocapnic hypoxia (10% 02 in N2 and 3-4% C02 for 3 months). The peptidergic innervation in the enlarged carotid bodies was different from that in the normoxic control carotid bodies. The density of SP and CGRP fibers in the chronically hypoxic carotid body decreased significantly to under 50 %, the density of VIP fibers increased significantly 1.80 times, and the density of NPY fibers were unchanged. Three-dimensional analysis showed that these peptidergic fibers are mainly associated with expanded vasculatures. In addition, the density of NOS-containing nerve fibers in the hypoxic carotid bodies was significantly decreased. These morphological results suggest that altered innervation of the chronica1ly hypoxic carotid body is one feature of hypoxic adaptation. Because these neuropeptides are vasoactive in nature, altered carotid body circulation may contribute to modulation of the chemosensory mechanisms by chronic hypoxia, and because it has been considered that nitric oxide (NO) is an inhibitory neuronal messenger in the normoxic carotid body, the present findings suggest that the sensory mechanisms in the hypoxic carotid body may be involved in 'disinhibition' resulting from reduced NO synthesis.Hypoxic and chemical stimuli increased intracellular Ca^<2+> in the glomus cells (chemoreceptor cells), but did not increase intracellular Ca^<2+> in about 20% of glomus cells in the cluster. These physiological results suggest that free Ca^<2+> may be produced from intracellular binding Ca^<2+> in response to the stimuli, and also that glomus cells with increased intracellular Ca^<2+> may hyperpolarize through the activation of calcium-dependent potassium channels.

在暴露于慢性等二氧化碳缺氧（在N2中10%O2和3- 4%CO2持续3个月）的大鼠中，颈动脉体（其是用于感测动脉血气和氢离子浓度变化的主要感觉器官）增大。颈动脉体的肽能神经支配与常氧对照颈动脉体不同。慢性缺氧组颈动脉体内SP、CGRP纤维密度显著降低，降至50%以下，VIP纤维密度显著增加1.80倍，NPY纤维密度无明显变化。三维分析表明，这些肽能纤维主要与扩张的血管有关。另外，缺氧组颈动脉体内NOS阳性神经纤维密度明显降低。这些形态学结果表明，慢性缺氧颈动脉体神经支配的改变是缺氧适应的特征之一。因为这些神经肽本质上是血管活性的，所以改变的颈动脉体循环可能有助于慢性缺氧对化学感受机制的调节，并且因为已经认为一氧化氮（NO）是含氧量正常的颈动脉体中的抑制性神经元信使，目前的研究结果表明，缺氧颈动脉体的感觉机制可能参与了NO合成减少导致的“去抑制”。化学刺激增加了血管球细胞（化学感受器细胞）的胞内Ca^2+，但在簇中约20%的血管球细胞中，胞内Ca^2+没有增加。这些生理学结果表明，游离Ca^2+可能是由细胞内结合Ca^2+对刺激作出反应而产生的，而且细胞内Ca^2+增加的血管球细胞可能通过激活钙依赖性钾通道而升高。