Subtype-specific beta-adrenoceptor signaling pathways in the heart and their potential clinical implications

作者：Xiao RP^*; Zhu WZ; Zheng M; Chakir K; Bond R; Lakatta EG; Cheng HP

来源：Trends in Pharmacological Sciences, 2004, 25(7): 358-365.

DOI：10.1016/j.tips.2004.05.007

beta-Adrenoceptor stimulation serves as the most powerful means to increase cardiac output in response to stress or exercise. However, sustained beta(2)-adrenoceptor stimulation promotes pathological cardiac remodeling such as myocyte hypertrophy and apoptosis, thus contributing to heart failure. Coexisting cardiac beta-adrenoceptor subtypes, mainly beta(1)-adrenoceptors and beta(2)-adrenoceptors, activate different signaling cascades with beta(1)-adrenoceptors coupling to G(s) and beta(2)-adrenoceptors coupling to G(s) and G(i) pathways. As a result, sustained beta(2)-adrenoceptor stimulation protects cardiomyocytes against apoptosis via a G(1)-phosphatidylinositol 3-kinaseprotein kinase B pathway, whereas chronic beta(1)-adrenoceptor stimulation induces myocyte hypertrophy and apoptosis by protein kinase A-independent activation of calmodullin kinase II signaling. These advances in our understanding of beta-adrenoceptor subtype signaling identify the mechanisms that underlie the beneficial effects of beta-adrenoceptor antagonists and delineate the rationale for combining beta(1)-adrenoceptor blockade with beta(2)-adrenoceptor activation as a potential therapy for heart failure.

• 出版日期2004-7
• 单位北京大学