Endothelin receptor is coupled to phospholipase C via a pertussis toxin-insensitive guanine nucleotide-binding regulatory protein in vascular smooth muscle cells.

Takuwa, Yoh; Kasuya, Yoshitoshi; Takuwa, Noriko; Kudo, Michiyo; Yanagisawa, Masashi; Goto, Katsutoshi; Masaki, Τοmoh; Yamashita, Kamejiro

doi:10.1172/jci114488

Cited by 183 publications

(77 citation statements)

References 36 publications

(14 reference statements)

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“…Since the desensitization persisted >30 min, this latter possibility would require continued production of this substance even in the absence of ET. In this regard, studies in cultured vascular smooth muscle cells have shown prolonged binding of ET to its receptor (39,40) and prolonged ET-initiated activation of PKC after its removal from incubation solutions (41 Physiological implications AVP-stimulated PF in IMCD is subject to regulation by numerous factors ( 13,14,22), some of which likely have important autocrine-like activities ( 13,14). To date, the only locally produced substances shown to modulate renal concentrating capacity are PGs.…”

Section: Desensitization Ofet Effectmentioning

confidence: 99%

Endothelin inhibits vasopressin-stimulated water permeability in rat terminal inner medullary collecting duct.

Nadler¹,

Zimpelmann²,

Hébert³

1992

J. Clin. Invest.

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Renal tubule solute and water transport is subject to regulation by numerous factors. To characterize direct effects of the recently discovered peptide endothelin (ET) on renal tubule transport, we determined signaling mechanisms for ET effects on vasopressin (AVP)-stimulated water permeability (PF) in rat terminal inner medullary collecting duct (IMCD) perfused in vitro. ET caused a rapid, dose-dependent, and reversible fall in AVP-but not cyclic AMP-stimulated PFI suggesting that its effect on PF is by inhibition of cyclic AMP accumulation. Indomethacin did not block ET actions, ruling out a role for prostaglandins in its effect. The protein kinase C (PKC) inhibitor calphostin, or pretreatment of perfused tubules with pertussis toxin, blocked ET-mediated inhibition of AVP-stimulated PF.ET caused a transient increase in intracellular calcium ([Ca2"J1)

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Section: Desensitization Ofet Effectmentioning

confidence: 99%

Endothelin inhibits vasopressin-stimulated water permeability in rat terminal inner medullary collecting duct.

Nadler¹,

Zimpelmann²,

Hébert³

1992

J. Clin. Invest.

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“…A similar initial gradual rise in the intracellular Ca 2+ concentration is also found in ET-1-stimulated coronary strips (4). The molecular character ization of the initial signal transduction path way does not clearly distinguish ET from other vasoactive agonists (3,12,13). Further investigations are required to resolve the mechanisms for the slow kinetics of these pa rameters in ET-stimulated vascular smooth muscle.…”

mentioning

confidence: 90%

“…DPB, a protein kinase C activator, but not 60 mM KCI has a similar effect on caldesmon phosphorylation. Since ET stimulates phospholipase C to produce 1,2 diacylglycerol, leading to protein kinase C activation (2,3,5,14), these results suggest that ET-induced caldesmon phosphorylation may be mediated directly or indirectly through protein kinase C. Recent studies (15) sug gested that the regulatory function of caldes mon might be altered by its phosphorylation state. Adam et al (8,15) reported that in intact porcine carotid artery stimulated with phorbol 12,13-dibutyrate (PDB), the phos phorylation level of caldesmon increased with a rather slow time course, consistent with the present results.…”

mentioning

confidence: 97%

Endothelin-1-Induced Phosphorylation of the 20-kDa Myosin Light Chain and Caldesmon in Porcine Coronary Artery Smooth Muscle.

et al. 1991

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Endothelin-1 (ET), a potent vasoconstrictor, induces a sustained in crease in the phosphorylation level of the 20-kDa myosin light chain (MLC) in por cine coronary artery strips. ET also induces late phosphorylation of caldesmon, which is mimicked by 12-deoxyphorbol 13-isobutyrate, but not by 60 mM KC1. Nitroglycerin, a vasorelaxant, completely reverses the ET-induced phosphorylation of MLC, but not that of caldesmon. These results suggest an important regulatory role of MLC phos phorylation in ET-induced contraction.Endothelin-1 (ET) is one of the most potent vasoconstrictors to be discovered (1). Our pre vious studies (2-4) as well as observations by other investigators (5) demonstrate that ET receptor activation in vascular smooth muscle leads to the activation of phospholipase C and Ca 2+ channels, resulting in an increase in the intracellular free Ca 2+ concentration and the activation of protein kinase C. However, it is not known how ET-1 activates the contractile mechanism following the generation of the second messengers. To understand in more detail the mechanism of the ET-induced con traction of vascular smooth muscle, phos phorylation changes of the proteins thought to be involved in the regulation of contraction were explored in porcine coronary smooth muscle. Particularly, we studied the time-de pendent changes in the extent of the Ca 2+ and calmodulin-dependent phosphorylation of 20-kDa myosin light chain (MLC), which is known to serve as a specific signal for initiat ing cross bridge cycling (6), and phosphoryla tion of caldesmon, a calmodulin-binding, thin filament-associated protein (7,8).Porcine right coronary arteries were dis sected and carefully cleared of adhering con nective tissue (2, 4). Transverse arterial strips of approximately 2-mm width were prepared for the experiments. Strips were mounted in 10-ml static muscle chambers and equilibrated in modified Krebs-Henseleit bicarbonate buf fer containing 10-5 M phentolamine and 10-6 M atropin (9) aerated with 95% 02/5% CO2 at 37°C. Tension was isometrically measured with a Nihon Kohden TB-611T force-displace ment transducer and displayed on a Nihon Kohden WT-647G recorder. The tension in re sponse to agonist stimulation was expressed as a percent of the maximal response to KCl (110 mM). To measure the phosphorylation of 20

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“…ET-1 binds to ET A receptors on the cell surface, and these receptors are classical heptathelical G-protein coupled receptors that activate phospholipase C to cause hydrolysis of phosphatidyl inositol and generation of cytosolic inositol triphosphate and membrane-bound diacylglycerol, which accelerate protein kinase C (PKC) activity and intracellular Ca 2+ concentration. 33) It has been reported that a PKC activator, such as TPA, reduces elastin expression by a posttranscriptional mechanism. It has also been postulated that TPA may control the tropoelastin mRNA via unique cis-acting sequences of the 3′ untranslated region (3′UTR).…”

Section: Discussionmentioning

confidence: 99%

Endothelin-1 Down-Regulates Expression of Tropoelastin and Lysyl Oxidase mRNA in Cultured Chick Aortic Smooth Muscle Cells.

Wachi

Sugitani

Tajima

et al. 2001

JOURNAL OF HEALTH SCIENCE

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Endothelin-1 (ET-1) is known as a potent stimulator of cell proliferation and as a vasoconstrictor. It is believed that ET-1 contributes to the development of arterial diseases such as atherosclerosis. In this study, we demonstrated the expression of tropoelastin and lysyl oxidase (LO) on gene levels as induced by ET-1 in cultured smooth muscle cells (SMCs). ET-1 stimulated cell proliferation in a dose-dependent manner, and the level of this proliferation increased about 1.3-fold at 100 nM of ET-1. ET-1 suppressed the tropoelastin protein synthesis in a dose-dependent and time-dependent manner. In addition, ET-1 dose-dependently suppressed the tropoelastin and LO mRNA expression. The tropoelastin and LO mRNA levels decreased to about half and 4/5, respectively, at 100 nM of ET-1. The inhibition of elastin synthesis was completely prevented by BQ123, an endothelin receptor A (ET A ) antagonist. These results indicate that ET-1 can modulate the tropoelastin and LO mRNA expression via an ET A receptor in cultured SMC and that the regulator for elastin expression may play an important role in elastogenesis and SMC proliferation during the development of atherosclerosis.

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Endothelin receptor is coupled to phospholipase C via a pertussis toxin-insensitive guanine nucleotide-binding regulatory protein in vascular smooth muscle cells.

Abstract: The mechanisms of endothelin-1 (ET) actions were investigated in cultured rat aortic vascular smooth muscle A-10 cells.

Cited by 183 publications

References 36 publications

Endothelin inhibits vasopressin-stimulated water permeability in rat terminal inner medullary collecting duct.

Endothelin inhibits vasopressin-stimulated water permeability in rat terminal inner medullary collecting duct.

Endothelin-1-Induced Phosphorylation of the 20-kDa Myosin Light Chain and Caldesmon in Porcine Coronary Artery Smooth Muscle.

Endothelin-1 Down-Regulates Expression of Tropoelastin and Lysyl Oxidase mRNA in Cultured Chick Aortic Smooth Muscle Cells.

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