Godinho Rosely O, Duarte Thiago, Pacini Enio S A
Disciplina Farmacologia Celular, Departamento de Farmacologia, Escola Paulista de Medicina, Universidade Federal de São Paulo São Paulo, Brazil.
Front Pharmacol. 2015 Mar 24;6:58. doi: 10.3389/fphar.2015.00058. eCollection 2015.
G protein-coupled receptors (GPCRs) linked to stimulatory G (Gs) proteins (GsPCRs) mediate increases in intracellular cyclic AMP as consequence of activation of nine adenylyl cyclases , which differ considerably in their cellular distribution and activation mechanisms. Once produced, cyclic AMP may act via distinct intracellular signaling effectors such as protein kinase A and the exchange proteins activated by cAMP (Epacs). More recently, attention has been focused on the efflux of cAMP through a specific transport system named multidrug resistance proteins that belongs to the ATP-binding cassette transporter superfamily. Outside the cell, cAMP is metabolized into adenosine, which is able to activate four distinct subtypes of adenosine receptors, members of the GPCR family: A1, A2A, A2B, and A3. Taking into account that this phenomenon occurs in numerous cell types, as consequence of GsPCR activation and increment in intracellular cAMP levels, in this review, we will discuss the impact of cAMP efflux and the extracellular cAMP-adenosine pathway on the regulation of GsPCR-induced cell response.
与刺激性G蛋白（Gs）偶联的G蛋白偶联受体（GsPCRs）通过激活9种腺苷酸环化酶介导细胞内环磷酸腺苷（cAMP）水平升高，这些腺苷酸环化酶在细胞分布和激活机制上有很大差异。一旦产生，cAMP可通过不同的细胞内信号效应器发挥作用，如蛋白激酶A和由cAMP激活的交换蛋白（Epacs）。最近，人们的注意力集中在cAMP通过一种名为多药耐药蛋白的特定转运系统流出，该转运系统属于ATP结合盒转运体超家族。在细胞外，cAMP被代谢为腺苷，腺苷能够激活GPCR家族的四种不同亚型的腺苷受体：A1、A2A、A2B和A3。鉴于这种现象在多种细胞类型中都会发生，是GsPCR激活和细胞内cAMP水平升高的结果，在本综述中，我们将讨论cAMP流出和细胞外cAMP-腺苷途径对GsPCR诱导的细胞反应调节的影响。
