Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, The University of Nottingham, Nottingham, UK.
Br J Pharmacol. 2012 May;166(2):401-10. doi: 10.1111/j.1476-5381.2011.01719.x.
Since its discovery over 50 years ago, cAMP has been the archetypal second messenger introducing students to the concept of cell signalling at the simplest level. As explored in this review, however, there are many more facets to cAMP signalling than the path from Gs-coupled receptor to adenylyl cyclase (AC) to cAMP to PKA to biological effect. After a brief description of this canonical cAMP signalling pathway, a snapshot is provided of the novel paradigms of cAMP signalling. As in the airway the cAMP pathway relays the major bronchorelaxant signal and as such is the target for frontline therapy for asthma and COPD, particular emphasis is given to airway disease and therapy. Areas discussed include biased agonism, continued signalling following internalization, modulation of cAMP by AC, control of cAMP degradation, cAMP and calcium crosstalk, Epac-mediated signalling and finally the implications of altered genotypes will be considered. LINKED ARTICLES This article is part of a themed section on Novel cAMP Signalling Paradigms. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue-2.
自 50 多年前发现以来，cAMP 一直是典型的第二信使，在最简单的层面上向学生介绍细胞信号转导的概念。然而，正如本文所探讨的，cAMP 信号传递的方面远不止 Gs 偶联受体到腺苷酸环化酶（AC）到 cAMP 到 PKA 到生物学效应这一途径。在简要描述了这条典型的 cAMP 信号通路之后，本文提供了 cAMP 信号传递新范例的快照。正如在气道中，cAMP 通路传递主要的支气管舒张信号，并且是哮喘和 COPD 的一线治疗靶点，因此特别强调了气道疾病和治疗。讨论的领域包括偏性激动剂、内化后持续信号传递、AC 对 cAMP 的调节、cAMP 降解的控制、cAMP 和钙的串扰、Epac 介导的信号传递以及改变的基因型的影响。
链接文章 本文是关于新型 cAMP 信号传递范例的专题部分的一部分。要查看该部分中的其他文章，请访问 http://dx.doi.org/10.1111/bph.2012.166.issue-2。
