Subcellular β-Adrenergic Receptor Signaling in Cardiac Physiology and Disease.
Subcellular β-Adrenergic Receptor Signaling in Cardiac Physiology and Disease.
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DOI：
10.1097/fjc.0000000000001324
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发表时间：
2022-09-01
影响因子：
3
通讯作者：
Smrcka, Alan, V
中科院分区：
文献类型：
--
作者：
Wei, Wenhui;Smrcka, Alan, V
关键词：
肾上腺素能受体是心脏功能的关键调节剂，在交感神经刺激期间对心输出量产生深远影响。在心脏应激条件下，心脏肾上腺素能系统的慢性刺激会导致心脏功能障碍、肥大，并最终导致衰竭。新数据表明，细胞内区室中的 G 蛋白偶联受体具有功能活性，可调节与细胞表面不同的细胞过程。 β2 肾上腺素能受体内化到各种细胞类型的内体上，最近显示它们能够持续刺激 cAMP 产生，从而选择性地调节基因表达。其他研究已经确定了核膜和高尔基体上的 β1 肾上腺素受体。在这里，我们讨论心脏中 β1 和 β2 肾上腺素能受体信号传导的数据，以及它们的亚细胞位置对其在心肌细胞和心脏病理学中不同生理功能的可能影响。了解这些受体在这些位置的相对作用可能会对这些受体治疗心力衰竭和心脏病的药理学靶向产生重大影响。
Adrenergic receptors are critical regulators of cardiac function with profound effects on cardiac output during sympathetic stimulation. Chronic stimulation of the adrenergic system of the heart under conditions of cardiac stress leads to cardiac dysfunction, hypertrophy, and ultimately failure. Emerging data have revealed that G protein coupled receptors in intracellular compartments are functionally active and regulate distinct cellular processes from those at the cell surface. β2 adrenergic receptors internalize onto endosomes in various cell types where they have recently been shown to continue to stimulate cAMP production to selectively regulate gene expression. Other studies have identified β1 adrenergic receptors at the nuclear envelope and the Golgi apparatus. Here we discuss data on signaling by β1 and β2 adrenergic receptors in the heart and the possible influence of their subcellular locations on their divergent physiological functions in cardiac myocytes, and in cardiac pathology. Understanding the relative roles of these receptors at these locations could have a significant impact on pharmacological targeting of these receptors for the treatment of heart failure and cardiac diseases.