Adrenomedullin-induced relaxation of rat brain pericytes is related to the reduced phosphorylation of myosin light chain through the cAMP/PKA signaling pathway
Adrenomedullin-induced relaxation of rat brain pericytes is related to the reduced phosphorylation of myosin light chain through the cAMP/PKA signaling pathway
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DOI：
10.1016/j.neulet.2008.10.082
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发表时间：
2009-01-02
影响因子：
2.5
通讯作者：
Kataoka, Yasufumi
中科院分区：
文献类型：
--
作者：
Takata, Fuyuko;Dohgu, Shinya;Kataoka, Yasufumi
已知脑周细胞包围脑微血管的近腔内皮表面。这些细胞中丰富的收缩蛋白的表达表明脑血流量的细胞周调节。在这里，我们研究了内皮源性舒张因子肾上腺髓质素能够诱导大鼠原代培养的脑周细胞舒张的分子机制。肾上腺髓质素增加了松弛的周细胞的相对比例，如细胞表面积增加所示。肾上腺髓质素的较小片段（肾上腺髓质素（22-52））阻断肾上腺髓质素诱导的舒张。肾上腺髓质素增加细胞内cAMP浓度，减少肌球蛋白轻链（MLC）的磷酸化。PKA抑制剂H89可抑制肾上腺髓质素诱导的松弛周细胞数的增加，使MLC磷酸化水平恢复到对照水平。本研究的结果表明，肾上腺髓质素诱导的脑周细胞的舒张作用与通过cAMP/PKA减少MLC的磷酸化有关。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Brain pericytes are known to embrace the abluminal endothelial surfaces of cerebral microvessels. The rich expression of contractile proteins in these cells suggests pericytal regulation of cerebral blood flow. Here, we investigated the molecular mechanisms by which an endothelium-derived relaxing factor, adrenomedullin, was able to induce the relaxation of rat primary cultured brain pericytes. Adrenomedullin increased the relative proportion of pericytes that were relaxed, as shown by an increased cell surface area. A smaller fragment of adrenomedullin (adrenomedullin(22-52)) blocked the adrenomedullin-induced relaxation. Adrenomedullin increased intracellular CAMP concentrations and decreased the phosphorylation of myosin light chain (MLC). H89 (a PKA inhibitor) inhibited the adrenomedullin-induced increase in the number of relaxed pericytes, and returned the level of phosphorylation of MLC to the control level. The results of the present study suggest that adrenomedullin-induced relaxation of brain pericytes is related to the reduced phosphorylation of MLC through cAMP/PKA. (C) 2008 Elsevier Ireland Ltd. All rights reserved.