Werry Tim D, Wilkinson Graeme F, Willars Gary B
Department of Cell Physiology and Pharmacology, Medical Sciences Building, University of Leicester, UK.
Biochem J. 2003 Sep 1;374(Pt 2):281-96. doi: 10.1042/BJ20030312.
Alteration in Ca(2+) (the intracellular concentration of Ca(2+)) is a key regulator of many cellular processes. To allow precise regulation of Ca(2+) and a diversity of signalling by this ion, cells possess many mechanisms by which they are able to control Ca(2+) both globally and at the subcellular level. Among these are many members of the superfamily of GPCRs (G-protein-coupled receptors), which are characterized by the presence of seven transmembrane domains. Typically, those receptors able to activate PLC (phospholipase C) enzymes cause release of Ca(2+) from intracellular stores and influence Ca(2+) entry across the plasma membrane. It has been well documented that Ca(2+) signalling by one type of GPCR can be influenced by stimulation of a different type of GPCR. Indeed, many studies have demonstrated heterologous desensitization between two different PLC-coupled GPCRs. This is not surprising, given our current understanding of negative-feedback regulation and the likely shared components of the signalling pathway. However, there are also many documented examples of interactions between GPCRs, often coupling preferentially to different signalling pathways, which result in a potentiation of Ca(2+) signalling. Such interactions have important implications for both the control of cell function and the interpretation of in vitro cell-based assays. However, there is currently no single mechanism that adequately accounts for all examples of this type of cross-talk. Indeed, many studies either have not addressed this issue or have been unable to determine the mechanism(s) involved. This review seeks to explore a range of possible mechanisms to convey their potential diversity and to provide a basis for further experimental investigation.
细胞内钙离子浓度（Ca(2+)）的改变是许多细胞过程的关键调节因子。为了精确调节Ca(2+)以及该离子的多种信号传导，细胞拥有多种机制，能够在整体和亚细胞水平上控制Ca(2+)。其中包括G蛋白偶联受体（GPCRs）超家族的许多成员，其特征是具有七个跨膜结构域。通常，那些能够激活磷脂酶C（PLC）的受体可导致细胞内储存的Ca(2+)释放，并影响Ca(2+)跨质膜进入。已有充分证据表明，一种类型的GPCR的Ca(2+)信号传导可受到另一种不同类型GPCR刺激的影响。实际上，许多研究已经证明了两种不同的PLC偶联GPCR之间的异源脱敏。鉴于我们目前对负反馈调节以及信号通路可能共享成分的理解，这并不奇怪。然而，也有许多记录在案的GPCR之间相互作用的例子，这些相互作用通常优先与不同的信号通路偶联，从而导致Ca(2+)信号增强。这种相互作用对细胞功能的控制和基于体外细胞的检测的解释都具有重要意义。然而，目前尚无单一机制能够充分解释这类串扰的所有例子。实际上，许多研究要么没有涉及这个问题，要么无法确定其中涉及的机制。本综述旨在探索一系列可能的机制，以展示其潜在的多样性，并为进一步的实验研究提供基础。
