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

Abstract

Gαq-coupled receptors such as α1-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 Gα12 and Gα13. In this report, we determined whether these G proteins interact with endothelin, angiotensin, and α1-adrenergic receptors in the human heart. We find that these receptors activate cardiac Gα12 and Gα13 differentially; endothelin receptors activate only Gα12 (to 218 ± 22% of unstimulated levels), angiotensin receptors activate only Gα13 (to 236 ± 49% of unstimulated levels), and α1-adrenergic receptors activate neither Gα12 (123 ± 18% of unstimulated levels) nor Gα13 (113 ± 12% of unstimulated levels). Consistent with these data, translocation of guanine nucleotide exchange factor p115RhoGEF, which responds to Gα13, occurs only after stimulation of angiotensin receptors (shifting from 73 ± 12% to 41 ± 10% cytosolic). These differences in the activation of Gα12 and Gα13 by Gαq-coupled receptors may underlie reported differences in the functions of these receptors.