کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9895200 | 1542747 | 2005 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Nongenomic effects of mineralocorticoid receptor activation in the cardiovascular system
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Fifteen years ago Wehling and colleagues showed unequivocal rapid effects of aldosterone, neither mimicked by cortisol nor blocked by spironolactone, and postulated that these nongenomic effects are mediated via a membrane receptor distinct from the classical mineralocorticoid receptor (MR). Several recent studies have challenged this view. Alzamora et al. showed 11β-hydroxysteroid denydrogenase 1 and 2 (11βHSD1, 11βHSD2) expression in human vascular smooth muscle cells, and that aldosterone rapidly raises intracellular pH via sodium-hydrogen exchange; cortisol is without effect and spironolactone does not block the aldosterone response. When, however, 11βHSD activity is blocked by carbenoxolone, cortisol shows agonist effects indistinguishable from aldosterone; in addition, the effect of both aldosterone and cortisol is blocked by the open E-ring, water soluble MR antagonist RU28318. In rabbit cardiomyocytes, aldosterone increases intracellular [Na+] by activating Na+/K+/2Clâ cotransport, with secondary effects on Na+/K+ pump activity. Pump current rises â¼10-fold within 15â², is unaffected by actinomycin D or the MR antagonist canrenone, and not elevated by cortisol. Pump current is, however, completely blocked by the open E-ring, water soluble MR antagonist K+ canrenoate and stoichometrically by cortisol. PKCÉ agonist peptides (but not PKCα, PKCδ or scrambled PKCÉ peptides) mimic the effect of aldosterone, and PKCÉ antagonist peptides block the effect. Very recently, cortisol has been shown to mimic the effect of aldosterone when cardiomyocyte redox state is altered by the installation of oxidized glutathione (GSSG) via the pipet, paralleling the effect of carbenoxolone on vascular smooth cells and suggesting possible pathophysiologic roles for an always glucocorticoid occupied MR.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Steroids - Volume 70, Issues 5â7, MayâJune 2005, Pages 347-351
Journal: Steroids - Volume 70, Issues 5â7, MayâJune 2005, Pages 347-351
نویسندگان
Anastasia S. Mihailidou, John W. Funder,