Endothelin stimulates phospholipase C, Na+/H+ exchange, c-fos expression, and mitogenesis in rat mesangial cells.

Simonson, Michael S.; Wann, Shianq; Menè, Paolo; Dubyak, George R.; Kester, Mark; Nakazato, Yuichi; Sedor, John R.; Dünn, Michael J.

doi:10.1172/jci113935

Cited by 564 publications

(222 citation statements)

References 36 publications

Supporting

Mentioning

210

Contrasting

Unclassified

Order By: Relevance

“…1, Table I). 1 pM ET-1, which generates only a monophasic, slow but sustained elevation of [Ca2+], (14), failed to induce mesangial cell contraction (Table I). In contrast, two concentrations of ET-1 (1.0 nM and 0.1 ,uM) that mobilize intracellular Ca2+ via activation of phospholipase C (14) increased the percentage of contracted cells above control (Table I) (Table I).…”

Section: Resultsmentioning

confidence: 99%

“…Using micropuncture, Badr and co-workers (10) documented increased glomerular afferent and efferent arteriolar resistance and a dramatic decline in the ultrafiltration coefficient, Kf, in response to ET- 1. Although the precise mechanism controlling Kf remains uncertain, the currently favored hypothesis is that contraction of mesangial cells, which are glomerular microvascular pericytes, decreases Kf by reducing filtration surface area (see 1 1-13 for review). We previously reported that ET-1 evokes two distinct patterns of Ca2' signaling in cultured rat mesangial cells ( 14). ET-l at 0.1-10.0 pM caused a modest but sustained elevation of [Ca2+]1 that depended on Ca2' entry.…”

Section: Introductionmentioning

confidence: 92%

“…ET-l at 0.1-10.0 pM caused a modest but sustained elevation of [Ca2+]1 that depended on Ca2' entry. In contrast, higher doses of ET-1 (0.1-100.0 nM) caused a rapid, transient increase in [Ca2+]i followed by a lower, sustained phase (14). The transient phase of [Ca2+]J correlated with activation of phospholipase C and the release of inositol-1,4,5-trisphosphate, which mobilizes Ca2' from intracellular stores (15).…”

Section: Introductionmentioning

confidence: 93%

See 2 more Smart Citations

Endothelin-1 stimulates contraction of rat glomerular mesangial cells and potentiates beta-adrenergic-mediated cyclic adenosine monophosphate accumulation.

Simonson¹,

Dünn²

1990

J. Clin. Invest.

Self Cite

161

View full text Add to dashboard Cite

The newly isolated peptide, endothelin-1 (ET-1), is a potent pressor agent that reduces GFR and the glomerular ultrafiltration coefficient. Recent evidence demonstrates that ET-1 mobilizes intracellular Ca2" (ICa2+Ii) in glomerular mesangial cells by activating the phosphoinositide cascade. The present experiments were designed to examine whether ET-1 stimulates mesangial cell contraction and regulates the synthesis of PGE2 and cAMP, which dampen vasoconstrictor-induced mesangial contraction. ET-1 (2 1 nM) reduced the cross-sectional area of rat mesangial cells cultured on three-dimensional gels of collagen type I. ET-1 also caused complex rearrangements of F-actin microfilaments consistent with a motile response. Contraction in response to ET-1 occurred only at concentrations that activate phospholipase C, and contraction was unaffected by blockade of dihydropyridine-sensitive C(a2+ channels.Elevation of [Ca2J11 with ionomycin, to equivalent concentrations of [Ca2I1i achieved with ET-1, also reduced mesangial cell cross-sectional area. ET-1 (0.1 isM) also evoked IH]arachidonate release and a fivefold increase in PGE2 synthesis as well as increased synthesis of PGF2. and small changes of TXB2. ET-1 caused a minor increase in intracellular cAMP accumulation only in the presence of 3-isobutyl-1-methylxanthine. ET-1 also amplified cAMP production in response to isoproterenol. TPA and ionomycin, alone and in combination, failed to mimic the potentiating effect of ET-1; however, indomethacin blocked ET-1-induced potentiation of isoproterenolstimulated cAMP, which was restored by addition of exogenous 10 nM PGE2. Thus the present data demonstrate that ET-1 stimulates mesangial cell contraction via pharmacomechanical coupling and activates phospholipase A2 to produce PGE2, PGFu, and TXB2. ET-1 also amplified ft adrenergicstimulated cAMP accumulation by a PGE2-dependent mechanism. (J. Clin. Invest. 1990. 85:790-797.)

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 93%

See 1 more Smart Citation

Endothelin-1 stimulates contraction of rat glomerular mesangial cells and potentiates beta-adrenergic-mediated cyclic adenosine monophosphate accumulation.

Simonson¹,

Dünn²

1990

J. Clin. Invest.

Self Cite

161

View full text Add to dashboard Cite

show abstract

“…Intensive studies have increased the knowledge on processing, pharmacological effects, receptors, signal transduction and antagonists of ETs [for review see 611]. As a mitogen, ET-1 has been reported to stimulate DNA synthesis in Swiss 3T3 fibroblasts [12][13][14], Rat-1 fibroblasts [15], rat mesangial cells [16] and glial cells [17].…”

Section: Introductionmentioning

confidence: 99%

Ultraviolet B irradiation increases endothelin‐1 and endothelin receptor expression in cultured human keratinocytes

et al. 1995

View full text Add to dashboard Cite

The effect of ultraviolet B (UVB) irradiation on endothelin-1 (ET-1) and ET receptor expression was examined using cultured normal human keratinocytes. Keratinocytes secreted ET-1 in the medium at a level of 2.1 pgldayllO s cells. UVB irradiation up to 10 mJIcm z increased ET-1 secretion 3-fold, and potentiated expression of mRNA for ET-1. Both ET A and ET R receptor mRNAs were detected in keratinocytes, and their expression was up-regulated by 5 mJ/cm 2 UVB irradiation.

show abstract

“…It also stimulates in vitro proliferation of mesangial cells, fibroblasts, and vascular smooth muscle cells (2)(3)(4). Endothelin production in endothelial cells is augmented by thrombin, transforming growth factor P (TGFP), and interleukin-l (5,6), some of which are known to be up-regulated in rheumatoid arthritis (RA).…”

mentioning

confidence: 99%

Increased production of endothelin‐1 in patients with inflammatory arthritides

Miyasaka

Hirata

Ando

et al. 1992

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Endothelin-1 (ET-1) is a potent vasoconstrictive peptide, but its precise mechanism of action in vivo has remained unknown.Methods. We measured ET-1 activity by radioimmunoassay, in both plasma and synovial fluid from patients with inflammatory arthritides.Results. ET-1-like immunoreactivity was found in synovial fluid, at levels severalfold higher than those in plasma. Reverse-phase high-performance liquid chromatography showed an elution profile corresponding to actual ET-1. A single class of high-atfinity binding sites for ET-1 in cultured synovial cells was also detected. Conclusion. Taken together, these results indicate that ET-1 might contribute to the synovial proliferation seen in inflammatory arthritides, in an autocrine/paracrine manner.Endothelin-I (ET-I), a 21-amino acid polypeptide with 2 intramolecular disulfide bonds, induces potent, sustained vasoconstriction in vitro and longlasting elevation of blood pressure in vivo (1). It also stimulates in vitro proliferation of mesangial cells, fibroblasts, and vascular smooth muscle cells (2-4). Endothelin production in endothelial cells is augmented by thrombin, transforming growth factor P (TGFP), and interleukin-l (5,6), some of which are known to be up-regulated in rheumatoid arthritis (RA). We therefore hypothesized that endothelin might be produced locally in the joints of patients with inflammatory arthritides. In the present study, we investigated this hypothesis and examined the possible role of endothelin in joint destruction. PATIENTS AND METHODSPatients. Twenty-three patients (18 women, 5 men; ages 39-82 years) who fulfilled the American College of Rheumatology (formerly, the American Rheumatism Association) criteria for RA (7), 11 patients (9 women, 2 men; ages 54-76 years) with osteoarthritis (OA) (5 of whom had inflammatory effusions in the knee), and 18 patients (all men; ages 34-58 years) with gout (4 of whom had acute knee arthritis with effusions) were entered into the study. Patients who were taking more than 5 mglday of prednisolone andlor 100 mglday of D-penicillamine were excluded from the study. RA patients were assigned to active or inactive

show abstract

Endothelin stimulates phospholipase C, Na+/H+ exchange, c-fos expression, and mitogenesis in rat mesangial cells.

Cited by 564 publications

References 36 publications

Endothelin-1 stimulates contraction of rat glomerular mesangial cells and potentiates beta-adrenergic-mediated cyclic adenosine monophosphate accumulation.

Endothelin-1 stimulates contraction of rat glomerular mesangial cells and potentiates beta-adrenergic-mediated cyclic adenosine monophosphate accumulation.

Ultraviolet B irradiation increases endothelin‐1 and endothelin receptor expression in cultured human keratinocytes

Increased production of endothelin‐1 in patients with inflammatory arthritides

Contact Info

Product

Resources

About