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Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts.

机译:大鼠心脏成纤维细胞中的腺苷受体和第二信使信号通路。

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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.
机译:腺苷(ADO)抑制心脏成纤维细胞(CF)中增殖和蛋白质合成(特别是胶原蛋白合成)的能力可改善心力衰竭患者中不良的心脏重塑和纤维化。然而,关于ADO可能在CF中调节以改变细胞表型的信号传导途径知之甚少。因此,本研究旨在鉴定成年大鼠CF的原代培养物中的ADO受体(AR)和与其相关的信号通路。定量RT-PCR数据表明,大鼠CF中存在所有四个已知AR(A(1)R,A(2a)R,A(2b)R和A(3)R)的mRNA,且患病率更高(2)受体亚型。没有耦合的AR到G(q)-磷脂酶C信号传导途径或钙的动员。使用亚型特异性试剂的研究表明,A(2a)R和A(2b)R与G(s)-腺苷酸环化酶偶联,而A(1)R与G(i)-腺苷酸环化酶偶联较弱。 2-氯代肌苷,5'-N-乙基羧酰胺基腺嘌呤和其他提高细胞cAMP的药物以对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。我们得出的结论是,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信号传导。

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