GPR30 expression is required for the mineralocorticoid receptor-independent rapid vascular effects of aldosterone.
It has been increasingly appreciated that steroids elicit acute vascular effects through rapid, so-called nongenomic signaling pathways. Though aldosterone, for example, has been demonstrated to mediate rapid vascular effects via both mineralocorticoid receptor-dependent and -independent pathways, the mechanism(s) of this mineralocorticoid receptor-independent effect of aldosterone is yet to be determined. For estrogen, its rapid effects have been reported to be, at least in part, mediated via the 7-transmembrane-spanning, G protein-coupled receptor GPR30. Previous studies have demonstrated common response outcomes in response to both aldosterone and estrogen on GPR30 expression, ie, activation of phosphatidylinositol 3-kinase-dependent contraction and extracellular signal-regulated kinase activation in vascular smooth muscle cells. The present studies were undertaken to test the hypothesis that the rapid response to aldosterone in smooth muscle is dependent on the availability of a GPR30-dependent signaling pathway. These findings not only reconcile differences in the literature for aldosterone response in freshly isolated versus cultured aortic smooth muscle cells but also suggest alternative therapeutic strategies for modulating aldosterone actions on the vasculature in vivo.
Departments of Medicine and Physiology & Pharmacology, Schulich School of Medicine & Dentistry, University of Western Ontario, and Vascular Biology Research Group, Robarts Research Institute, 100 Perth Drive, PO Box 5015, Stn B, London, ON, Canada. rgros@robarts.ca
Robert
R
Gros
Qingming
Q
Ding
Larry A
LA
Sklar
Eric E
EE
Prossnitz
Jeffrey B
JB
Arterburn
Jozef
J
Chorazyczewski
Ross D
RD
Feldman
D000450:Aldosterone / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011921:Rats, Inbred WKY; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000450:Aldosterone; D003345:Corticosterone; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019869:Phosphatidylinositol 3-Kinases; D043562:Receptors, G-Protein-Coupled; D018161:Receptors, Mineralocorticoid; C520305:Gper1 protein, rat
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