Berthouze Magali, Laurent Anne-Coline, Breckler Magali, Lezoualc'h Frank
INSERM, UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, 1 Avenue Jean Poulhès, BP 84225, 31342, Toulouse Cedex 4, France.
Curr Heart Fail Rep. 2011 Sep;8(3):159-67. doi: 10.1007/s11897-011-0062-8.
Cyclic adenosine 3',5'-monophosphate (cAMP) mediates the biological effects of various hormones and neurotransmitters. Stimulation of cardiac β-adrenergic receptors (β-AR) via catecholamines leads to activation of adenylyl cyclases and increases cAMP production to enhance myocardial function. Because many other receptors signaling through cAMP generation exist in cardiac myocytes, a central question is how different hormones induce distinct cellular responses through the same second messenger. A large body of evidence suggests that the localization and compartmentalization of β-AR/cAMP signaling affects the net outcome of biological functions. Spatiotemporal dynamics of cAMP action is achieved by various proteins, including protein kinase A (PKA), phosphodiesterases, and scaffolding proteins such as A-kinase-anchoring proteins. In addition, the discovery of the cAMP target Epac (exchange proteins directly activated by cAMP), which functions in a PKA-independent manner, represents a novel mechanism for governing cAMP-signaling specificity. Aberrant cAMP signaling through dysregulation of β-AR/cAMP compartmentalization may contribute to cardiac remodeling and heart failure.
环磷腺苷（cAMP）介导多种激素和神经递质的生物学效应。儿茶酚胺对心脏β-肾上腺素能受体（β-AR）的刺激会导致腺苷酸环化酶激活，增加cAMP生成，从而增强心肌功能。由于心肌细胞中存在许多其他通过生成cAMP进行信号传导的受体，一个核心问题是不同激素如何通过相同的第二信使诱导不同的细胞反应。大量证据表明，β-AR/cAMP信号的定位和区室化会影响生物学功能的最终结果。cAMP作用的时空动态是由多种蛋白质实现的，包括蛋白激酶A（PKA）、磷酸二酯酶以及诸如A激酶锚定蛋白等支架蛋白。此外，cAMP靶点Epac（直接由cAMP激活的交换蛋白）的发现，其以不依赖PKA的方式发挥作用，代表了一种控制cAMP信号特异性的新机制。通过β-AR/cAMP区室化失调导致的异常cAMP信号可能促成心脏重塑和心力衰竭。
