Department of Pharmacology, University of California at Davis, Davis, CA 95616; Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Trends Cardiovasc Med. 2013 Oct;23(7):250-6. doi: 10.1016/j.tcm.2013.02.001. Epub 2013 Mar 23.
Under β-adrenergic stimulation, the distribution of cAMP is highly restricted at distinct intracellular domains for compartmentalized activation of protein kinase A, which promotes selective phosphorylation of proteins for contractile responses in cardiomyocytes. This is primarily due to a concerted effort between restrictions of cAMP distribution by a family of phosphodiesterases and locally anchored protein kinase A by a family of scaffold A kinase-anchoring proteins. Moreover, these regulatory mechanisms underlie the cross talk between β-adrenergic signals and other receptor-stimulated signaling cascades, which alters the compartmentalized β-adrenergic signals for proper contractility in myocardium. Maintaining integrity of compartmentalized β-adrenergic signals is critical for physiological cardiac function and for preventing development of cardiac diseases.
在β肾上腺素能刺激下，cAMP 的分布在细胞内特定的区域受到高度限制，以实现蛋白激酶 A 的区室化激活，从而促进心肌细胞中收缩反应的蛋白选择性磷酸化。这主要是由于磷酸二酯酶家族限制 cAMP 分布和支架 A 激酶锚定蛋白家族局部锚定蛋白激酶 A 的协同作用。此外，这些调节机制是β肾上腺素能信号与其他受体刺激信号级联之间相互作用的基础，这种相互作用改变了心肌中局部化的β肾上腺素能信号，以实现适当的收缩性。维持局部化的β肾上腺素能信号的完整性对于心脏的生理功能和预防心脏疾病的发生至关重要。
