Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts
Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts
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DOI：
10.1152/ajpcell.00290.2008
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发表时间：
2009-05-01
影响因子：
5.5
通讯作者：
Villarreal, Francisco
中科院分区：
文献类型：
--
作者：
Epperson, Sara A.;Brunton, Laurence L.;Villarreal, Francisco
张建军，张建军，张建军，等。大鼠心肌成纤维细胞中腺苷受体和第二信使信号通路的研究。[J] .中国生物医学工程学报，2009,31(6):1158 - 1158。2009年2月25日首次出版；doi: 10.1152 / ajpcell.00290.2008。腺苷（ADO）抑制心脏成纤维细胞（CF）增殖和蛋白质合成（特别是胶原合成）的能力可能改善心力衰竭患者出现的不良心脏重构和纤维化。然而，关于ADO可能在CF中调节改变细胞表型的信号通路知之甚少。因此，本研究旨在鉴定成年大鼠CF原代培养中ADO受体（AR）及其相关的信号通路。定量RT-PCR数据表明，所有四种已知AR (A(1)R、A(2a)R、A（2b)R和A(3)R）的mrna都存在于大鼠CF中，其中A(2)受体亚型的发生率更高。没有测量到AR与G(q)-磷脂酶C信号通路或钙动员的偶联。使用亚型特异性药物的研究表明，A(2a)R和A(2b)R与G(s)-腺苷酸环化酶和A(1)R与G(i)-腺苷酸环化酶的偶联较弱。2-氯腺苷，5'- n-乙基羧胺腺苷和其他提高细胞cAMP的药物以百日咳毒素不敏感的方式刺激细胞外信号调节的激酶1/2活性。我们得出结论，通过a （2a）和a （2b）受体产生的camp依赖信号的组合可能介导成年大鼠CF中的ADO信号。
Epperson SA, Brunton LL, Ramirez-Sanchez I, Villarreal F. Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts. Am J Physiol Cell Physiol 296: C1171-C1177, 2009. First published February 25, 2009; doi:10.1152/ajpcell.00290.2008.-The ability of adenosine (ADO) to inhibit proliferation and protein synthesis (in particular, collagen synthesis) in cardiac fibroblasts (CF) may ameliorate adverse cardiac remodeling and fibrosis seen in heart failure patients. However, little is known about the signaling pathways that ADO may modulate in CF to alter cell phenotype. Accordingly, this study was designed to identify ADO receptors (AR) and the signaling pathways linked to them in primary cultures of adult rat CF. Quantitative RT-PCR data indicate that the mRNAs for all four known ARs (A(1)R, A(2a)R, A(2b)R, and A(3)R) are present in rat CF, with a greater prevalence of A(2) receptor subtypes. No coupling of AR to the G(q)-phospholipase C signaling pathway or to mobilization of calcium is measurable. Studies using subtype specific agents imply that the A(2a)R and A(2b)R couple to G(s)-adenylyl cyclase and A(1)R couple weakly to G(i)-adenylyl cyclase. 2-Chloroadenosine, 5'-N-ethylcarboxamidoadensoine, and other agents that elevate cellular cAMP stimulate extracellular signal-regulated kinase 1/2 activity in a pertussis toxin-insensitive manner. We conclude that a combination of cAMP-dependent signals generated via A(2a) and A(2b) receptors likely mediate ADO signaling in adult rat CF.