Selective activation of human atrial Galpha12 and Galpha13 by Galphaq-coupled angiotensin and endothelin receptors.
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.
Kilts
Jason D
JD
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
Lin
Shu S
SS
Lowe
James E
JE
Kwatra
Madan M
MM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000809:Angiotensins / Q000502:physiology; D020517:Atrial Appendage / Q000378:metabolism* / Q000502:physiology; D015153:Blotting, Western; D016232:Endothelins / Q000502:physiology; D005260:Female; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism* / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010656:Phenylephrine / Q000494:pharmacology; D019920:Photoaffinity Labels; D021381:Protein Transport; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism / Q000502:physiology; D011945:Receptors, Angiotensin / Q000378:metabolism* / Q000502:physiology; D017466:Receptors, Endothelin / Q000378:metabolism* / Q000502:physiology; D064067:Rho Guanine Nucleotide Exchange Factors
D000809:Angiotensins; D016232:Endothelins; D020662:Guanine Nucleotide Exchange Factors; D019920:Photoaffinity Labels; D018340:Receptors, Adrenergic, alpha-1; D011945:Receptors, Angiotensin; D017466:Receptors, Endothelin; D064067:Rho Guanine Nucleotide Exchange Factors; D010656:Phenylephrine; D044365:GTP-Binding Protein alpha Subunits, G12-G13