Endothelin (ET)-3 stimulates cyclic guanosine 3',5'-monophosphate production via ETB receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells.

Owada, Akira; Tomita, Kimio; Terada, Yoshio; Sakamoto, Hisato; Nonoguchi, Hiroshi; Marumo, Fumiaki

doi:10.1172/jci117007

Cited by 75 publications

(33 citation statements)

References 17 publications

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“…4 -6,16,22 NO has been postulated to function as an intermediate in signaling endothelin activity in a number of nephron segments, [23][24][25][26] including the IMCD. We asked whether either exogenous or endogenous ET would prove capable of regulating eNOS mRNA levels in the IMCD cell cultures.…”

Section: Resultsmentioning

confidence: 99%

Endothelin Inhibits NPR-A and Stimulates eNOS Gene Expression in Rat IMCD Cells

Chen

Gardner

2003

Hypertension

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Abstract-We have shown in previous studies that high extracellular tonicity is associated with increased expression of the type A natriuretic peptide receptor (NPR-A) and reduced expression of the endothelial NO synthase (eNOS) gene in cultured rat inner-medullary collecting duct cells. The vasoactive peptide endothelin has been shown to be avidly expressed in this nephron segment, and to be subject to osmotic regulation. We asked whether endothelin might play a role in the control of basal or osmotically regulated NPR-A or eNOS gene expression in these cells. Although exogenous endothelin had little or no effect on basal expression of eNOS mRNA or protein or NPR-A gene expression, both the type A (BQ610) and type B (IRL1038) endothelin receptor antagonists proved capable of reducing eNOS mRNA and protein expression, and increasing levels of the NPR-A mRNA. Increased extracellular tonicity reduced endothelin mRNA accumulation in these cells (Ϸ15% of control levels); however, exogenous endothelin failed to normalize osmotically increased NPR-A activity or expression, or osmotically suppressed eNOS expression. Collectively, these data demonstrate the presence of a number of independent but highly interactive local regulatory networks governing fluid and electrolyte handling in this distal nephron segment. Key Words: natriuretic peptides Ⅲ endothelin Ⅲ nitric oxide synthase Ⅲ osmotic regulation Ⅲ gene expression T he inner-medullary collecting duct (IMCD) plays a major role in the control of fluid and electrolyte homeostasis. Located in the terminal nephron, the IMCD samples up to 5% of filtered sodium load and bears ultimate responsibility for the regulation of urinary sodium concentration. 1 A number of local and systemic regulatory factors-including mineralocorticoids, prostaglandin E 2 , endothelin, interleukin-1, and atrial natriuretic peptide-signal events in the IMCD that ultimately result in changes in sodium excretion. 2 Endothelin is a vasoconstrictor peptide that was originally isolated from porcine endothelial cells. 3 It is produced as 3 isoforms (ET 1-3 ) that bind to 2 receptor subtypes (ET A and ET B ). ET is produced in the kidney and is particularly enriched in IMCDs, 4 -6 where it has been shown to promote natriuretic activity. 7 Both ET A and ET B receptors are expressed in IMCDs, 8 leading to the suggestion that ET may function as an autocrine/paracrine regulator of sodium and water transport in this terminal nephron segment. 9,10 A number of local and systemic factors have been shown to regulate ET expression in IMCDs, including immune cytokines 11 and extracellular tonicity. 12-14 The latter is particularly intriguing given the high osmolar environment surrounding the IMCD cell.We have shown previously that increased extracellular tonicity results in increased expression of the type A natriuretic peptide receptor (NPR-A) gene 15 and reduced expression of the endothelial NO synthase (eNOS) gene 16 in IMCD cells. In fact, the reduced basal concentrations of cyclic GMP resulting from the reduct...

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Section: Resultsmentioning

confidence: 99%

Endothelin Inhibits NPR-A and Stimulates eNOS Gene Expression in Rat IMCD Cells

Chen

Gardner

2003

Hypertension

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“…ET B receptor immunoreactivity of glomerular capillaries has previously been described (Hagiwara et al 1993;Yamamoto and Uemura 1998), whereas the presence of ET B receptors on mesangial cells could only be observed in culture (Owada et al 1994). ET A -receptor-mediated mitogenic effects of ET-1 on mesangial cells are well known and correlate with protective effects of ET A receptor antagonists on the development of glomerulosclerosis in animal studies (Simonson et al 1989;Wang et al 1994;Ebihara et al 1997;Dhein et al 2000).…”

Section: Et Receptors In Rat Kidneymentioning

confidence: 91%

Distribution of Endothelin Receptor Subtypes ET_A and ET_B in the Rat Kidney

Wendel

Knels

Kummer

et al. 2006

J Histochem Cytochem.

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(WK) S U M M A R Y The endothelin (ET) receptor system is markedly involved in the regulation of renal function under both physiological and pathophysiological conditions. The present study determined the detailed cellular localization of both ET receptor subtypes, ET A and ET B , in the vascular and tubular system of the rat kidney by immunofluorescence microscopy. In the vascular system we observed both ET A and ET B receptors in the media of interlobular arteries and afferent and efferent arterioles. In interlobar and arcuate arteries, only ET A receptors were present on vascular smooth muscle cells. ET B receptor immunoreactivity was sparse on endothelial cells of renal arteries, whereas there was strong labeling of peritubular and glomerular capillaries as well as vasa recta endothelium. ET A receptors were evident on glomerular mesangial cells and pericytes of descending vasa recta bundles. In the renal tubular system, ET B receptors were located in epithelial cells of proximal tubules and inner medullary collecting ducts, whereas ET A receptors were found in distal tubules and cortical collecting ducts. Distribution of ET A and ET B receptors in the vascular and tubular system of the rat kidney reported in the present study supports the concept that both ET receptor subtypes cooperate in mediating renal cortical vasoconstriction but exert differential and partially antagonistic effects on renal medullary function.

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“…Mesangial cell strains from male Sprague-Dawley rats were isolated and characterized as previously reported (23). Cells were cultured in an RPMI 1640 medium that contained 20% FBS, 100 units/ml penicillin, 100 g/ml streptomycin, 5 g/ml insulin, 5 g/ml transferrin, and 5 ng/ml selenite at 37°C in a 5% CO 2 incubator.…”

Section: Mesangial Cell Culture and Histologic Examinationmentioning

confidence: 99%

Aldosterone Stimulates Proliferation of Mesangial Cells by Activating Mitogen-Activated Protein Kinase 1/2, Cyclin D1, and Cyclin A

Terada¹,

Kobayashi²,

Kuwana³

et al. 2005

Journal of the American Society of Nephrology

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Recently, attention has been focused on the role of aldosterone in the pathophysiology of hypertension and cardiovascular disease. Several clinical and experimental data support the hypothesis that aldosterone contributes to the progression of renal injury. However, the molecular mechanisms of the effects of aldosterone in signal transduction and the cell-cycle progression of mesangial cells are not well known. For determining the signaling pathway of aldosterone in cultured mesangial cells, the effects of aldosterone on the mitogen-activated protein kinase 1/2 (MAPK1/2) pathway and the promoter activities of cyclin D1, cyclin A, and cyclin E were investigated. First, it was shown that the mineralocorticoid receptor (MR) was expressed in rat mesangial cells and glomeruli and that aldosterone stimulated the proliferation of mesangial cells via the MR and MAPK1/2 pathway. Next, it was demonstrated that aldosterone stimulated Ki-RasA, c-Raf kinase, MEK1/2, and MAPK1/2 in rat mesangial cells. Aldosterone induced cyclin D1 and cyclin A promoter activities and protein expressions, as well as the increments of CDK2 and CDK4 kinase activities. The presence of CYP11B2 and 11␤-HSD2 mRNA in rat mesangial cells also was shown. In conclusion, aldosterone seems to exert mainly MR-induced effects that stimulate c-Raf, MEK1/2, MAPK1/2, the activities of CDK2 and CDK4, and the cell-cycle progression in mesangial cells. MR antagonists may serve as a potential therapeutic approach to mesangial proliferative disease.

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Endothelin (ET)-3 stimulates cyclic guanosine 3',5'-monophosphate production via ETB receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells.

Cited by 75 publications

References 17 publications

Endothelin Inhibits NPR-A and Stimulates eNOS Gene Expression in Rat IMCD Cells

Endothelin Inhibits NPR-A and Stimulates eNOS Gene Expression in Rat IMCD Cells

Distribution of Endothelin Receptor Subtypes ET_A and ET_B in the Rat Kidney

Aldosterone Stimulates Proliferation of Mesangial Cells by Activating Mitogen-Activated Protein Kinase 1/2, Cyclin D1, and Cyclin A

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Endothelin (ET)-3 stimulates cyclic guanosine 3',5'-monophosphate production via ETB receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells.

Cited by 75 publications

References 17 publications

Endothelin Inhibits NPR-A and Stimulates eNOS Gene Expression in Rat IMCD Cells

Endothelin Inhibits NPR-A and Stimulates eNOS Gene Expression in Rat IMCD Cells

Distribution of Endothelin Receptor Subtypes ETA and ETB in the Rat Kidney

Aldosterone Stimulates Proliferation of Mesangial Cells by Activating Mitogen-Activated Protein Kinase 1/2, Cyclin D1, and Cyclin A

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Distribution of Endothelin Receptor Subtypes ET_A and ET_B in the Rat Kidney