Kilts Jason D, Lin Shu S, Lowe James E, Kwatra Madan M
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
J Cardiovasc Pharmacol. 2007 Sep;50(3):299-303. doi: 10.1097/FJC.0b013e3180a72632.
Galphaq-coupled receptors such as alpha1-adrenergic, angiotensin, and endothelin receptors, play key roles in cardiac physiology. These receptors have also been shown to couple to G proteins of the G12 family, including Galpha12 and Galpha13. In this report, we determined whether these G proteins interact with endothelin, angiotensin, and alpha1-adrenergic receptors in the human heart. We find that these receptors activate cardiac Galpha12 and Galpha13 differentially; endothelin receptors activate only Galpha12 (to 218 +/- 22% of unstimulated levels), angiotensin receptors activate only Galpha13 (to 236 +/- 49% of unstimulated levels), and alpha1-adrenergic receptors activate neither Galpha12 (123 +/- 18% of unstimulated levels) nor Galpha13 (113 +/- 12% of unstimulated levels). Consistent with these data, translocation of guanine nucleotide exchange factor p115RhoGEF, which responds to Galpha13, occurs only after stimulation of angiotensin receptors (shifting from 73 +/- 12% to 41 +/- 10% cytosolic). These differences in the activation of Galpha12 and Galpha13 by Galphaq-coupled receptors may underlie reported differences in the functions of these receptors.
与Gαq偶联的受体，如α1-肾上腺素能受体、血管紧张素受体和内皮素受体，在心脏生理学中发挥关键作用。这些受体也已被证明可与G12家族的G蛋白偶联，包括Gα12和Gα13。在本报告中，我们确定了这些G蛋白是否与人心脏中的内皮素、血管紧张素和α1-肾上腺素能受体相互作用。我们发现这些受体对心脏Gα12和Gα13的激活存在差异；内皮素受体仅激活Gα12（达到未刺激水平的218±22%），血管紧张素受体仅激活Gα13（达到未刺激水平的236±49%），而α1-肾上腺素能受体既不激活Gα12（为未刺激水平的123±18%）也不激活Gα13（为未刺激水平的113±12%）。与这些数据一致的是，对Gα13有反应的鸟嘌呤核苷酸交换因子p115RhoGEF的易位仅在血管紧张素受体刺激后发生（从胞质中的73±12%转变为41±10%）。Gαq偶联受体对Gα12和Gα13激活的这些差异可能是这些受体功能差异报道的基础。
