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Effect of PARs on the smooth muscles of arterioles, analyzing by bioimaging method

PARs对小动脉平滑肌的影响，通过生物成像方法分析

基本信息

批准号：
17390053
负责人：
SATOH Yoh-ichi
金额：
$ 8.97万
依托单位：
Iwate Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390053/
关键词：
Intracellular Calcium Ion Vascular smooth muscle Laser Scanning Confocal Microscopy Digital imaging Analysis Living Cell Tissue Specimens Protease Activated Receptors

项目摘要

Protease-activated receptors (PARs) mediate cellular responses to various proteases in numerous cell types, including smooth muscles and the endothelium of blood vessels. PARs may also play important roles in microcirculation in tissue/organs. The issue of whether the stimulation of PARs induces responses in smooth muscle cells of arterioles was examined; with special reference to intracellular Ca^<2+>([Ca^(2+)]i) dynamics and nitric oxide (NO) production during PARs stimulation, since [Ca^(2+) ]i and NO are both key factors in the maintenance of strain in blood vessels. These were measured by real-time confocal microscopy. Arterioles were taken obtained from the brain and testis of rats. In smooth muscle cells of small cerebral arterioles (< 50 μm in diameter), thrombin and PAR1-activating peptide (AP) induced an increase in [Ca^<2+>]i and contraction. The response to PAR1 activation was caused by Ca^<2+>mobilization from intracellular Ca^<2+>stores. Trypsin and PAR2-AP induced a decrease in [Ca^<2+>] i in the cells, and this effect can be mediated by endothelium-derived NO and/or by promoting. Ca^<2+> sequestration mechanism. PAR3- and 4-AP had no effect. In contrast to small cerebral arterioles, [Ca^<2+>], dynamics in smooth muscle cells of large (<100 μ in diameter) cerebral or testicular arterioles remained unchanged during PARs activation. In accordance with [Ca^<2+>], imaging results, immunohistochemical results showed thrombin receptor and PAR2 in smooth muscles and endothelium of small cerebral arterioles, but not in larger those. The immunoreactivity of PARs in testicular arterioles was faint. This is the first study to demonstrate the effects of PARs activation on the [Ca^<2+>]I dynamics of smooth muscles and the contraction/relaxation of cerebral arterioles, implicating the significant role of proteases in the regional tissue circulation of the brain.

蛋白酶激活受体（PAR）介导许多细胞类型（包括平滑肌和血管内皮）中对各种蛋白酶的细胞应答。PAR还可能在组织/器官的微循环中发挥重要作用。研究了PAR刺激是否诱导小动脉平滑肌细胞的反应的问题;特别是PAR刺激期间的细胞内Ca^2+（[Ca^（2+）]i）动力学和一氧化氮（NO）产生，因为[Ca^（2+）]i和NO都是维持血管应变的关键因素。这些通过实时共聚焦显微镜测量。取大鼠脑和睾丸的小动脉。在脑小动脉（直径< 50 μm）的平滑肌细胞中，凝血酶和PAR 1激活肽（AP）引起[Ca^<2+>]i增加和收缩。对PAR 1激活的反应是由细胞内Ca^2+库的Ca^2+动员引起的。胰蛋白酶和PAR 2-AP可诱导细胞内[Ca^2+] i降低，这种作用可能通过内皮源性NO和/或促进细胞内[Ca ^2+] i升高而介导。Ca^2+螯合机制。PAR 3-和4-AP没有影响。与大脑小动脉相反，大脑或睾丸大动脉（直径<100 μ）平滑肌细胞的[Ca^<2+>]动力学在PAR激活期间保持不变。与[Ca^<2+>]、影像学结果、免疫组化结果一致，凝血酶受体和PAR 2在脑小动脉平滑肌和内皮细胞中表达，而在脑大动脉中未见表达。PAR在睾丸小动脉中的免疫反应较弱。这是第一个证明PAR激活对平滑肌[Ca^<2+>]I动力学和脑小动脉收缩/舒张的影响的研究，暗示了蛋白酶在脑局部组织循环中的重要作用。