Selective Activation of Human Atrial Gα12 and Gα13 by Gαq-coupled Angiotensin and Endothelin Receptors

Abstract

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.