Cellular mechanism of action by a novel vasoconstrictor endothelin in cultured rat vascular smooth muscle cells

Hirata, Yukio; Yoshimi, Hiroki; Takata, Satoru; Watanabe, Toshifumi; Kumagai, Satoru; Nakajima, Kiichiro; Sakakibara, Shumpei

doi:10.1016/0006-291x(88)90220-3

Cited by 376 publications

(109 citation statements)

References 6 publications

Supporting

Mentioning

102

Contrasting

Order By: Relevance

“…These data are compatible with those of the ET-l-induced [Ca2+]i increase in cultured rat VSMC [4]. However, the failure of chelating extracellular Ca 2+ by EGTA and inhibiting voltage-dependent Ca2+-channels by nicardipine on ET-3-induced [Ca2+]i increase, strongly suggests that the rise of [Ca2+]i stimulated by ET-3 resulted from intracellular Ca z+ release rather than Ca 2+ influx from extracellular source.…”

Section: Discussionsupporting

confidence: 86%

“…Binding studies were performed essentially in the same manner as [~zSI]ET-1 binding to vascular smooth muscle cells (VSMC) as described [4]. Briefly, confluent ECs (-6 × 105 cells) were incubated with 2.5 × 10 -13 M [125I]ET-3 (spec.…”

Section: Binding Experimentsmentioning

confidence: 99%

“…After incubation in serum-free Dulbecco's modified Eagle's medium (DMEM) for 36 h, ECs were trypsinized and incubated with 4/~M fura-2 acetoxymethyl ester (Dojin Chemicals, Kumamoto, Japan) at 37°C for 20 min in Hepes-buffered physiological salt solution essentially in the same way as reported [4]. The fluorescence of CaZ+-fura-2 of the suspended cells (-5 × 106 cells/ml) was measured by a spectrofluorimeter (CAF-100; Jasco Co., Ltd., Tokyo, Japan) using excitation of 340 and 380 nm, and emission of 500 nm.…”

Section: Measurement Of Cytosolic Free Ca ;+ Concentration ([Ca;+]i)mentioning

confidence: 99%

See 2 more Smart Citations

Specific receptors for endothelin‐3 in cultured bovine endothelial cells and its cellular mechanism of action

1990

View full text Add to dashboard Cite

Among three endothelin (ET) isopeptides, ET-3 shows the most potent initial depressor response through the endothelium-dependent mechanism. We studied the presence of specific binding sites for ET-3 in cultured bovine endothelial cells (EC) and its cellular mechanism of action. Binding studies revealed the presence of two distinct subclasses of ET-3 receptors with high and low affinities. ET-3 dose-dependently (10 -1° 10 -7 M) increased both intracellular Ca z+ levels ([Ca2+]0 and inositol trisphosphate (IP3) formation. The ET-3-induced increase in [Ca2+]i was not affected by either removal of extracellular Ca 2+ or CaZ+-channel blockers. These data suggest that ET-3 induces phosphoinositide breakdown and increase in [Ca2+]i in ECs, possibly resulting from intracellular Ca z+ mobilization, thereby leading to vasodilatation.

show abstract

Section: Discussionsupporting

confidence: 86%

Section: Binding Experimentsmentioning

confidence: 99%

Section: Measurement Of Cytosolic Free Ca ;+ Concentration ([Ca;+]i)mentioning

confidence: 99%

See 1 more Smart Citation

Specific receptors for endothelin‐3 in cultured bovine endothelial cells and its cellular mechanism of action

1990

View full text Add to dashboard Cite

show abstract

“…Endothelin, in studies using porcine tissue, is synthesized from a precursor molecule, preproendothelin, by proteolytic cleavage (Itoh et al, 1988) and exhibits effects both on intact tissue ) and a culture derived from vascular smooth muscle cells Miasiro et al, 1988). These actions are mediated through binding sites which are specific for endothelin and distinct from catecholamine receptors or sites sensitive to dihydropyridines Hirata et al, 1988;Kanse et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

The pharmacological properties of the peptide, endothelin

Eglen¹,

Michel²,

Sharif³

et al. 1989

British J Pharmacology

View full text Add to dashboard Cite

1 The effect of endothelin (ET-1) has been studied on isolated vascular and non-vascular preparations, using both functional and competition radioligand binding techniques. The effects of endothelin on blood pressure were studied in both anaesthetised, chemically denervated normotensive and spontaneously hypertensive rats (SHR). 2 Endothelin elicited contractile responses in the rat thoracic aorta, perfused mesenteric bed, rabbit mesenteric artery and portal vein. The maximal responses in the rat aorta were enhanced by removal of the endothelium, and were reduced in the presence of either a cyclo-oxygenase inhibitor (indomethacin) or a thromboxane receptor antagonist (SQ 29,548). In terms of potency, the most sensitive preparation was the rat endothelium-denuded aorta and rat perfused mesenteric bed (-log EC50 values = 8.2 + 0.07 and 8.2 + 0.12, mean + s.e.mean, n = 4, respectively). In the perfused mesenteric bed of the rat the maximum response to endothelin (219 + 12 mmHg, n = 4) was greater than that to either phenylephrine (maximal response = 67 + 9 mmHg; n = 4) or KCl (maximal response = 110 + 6 mmHg, n = 4).3 Endothelin elicited contractile responses of the guinea-pig isolated ileum, oesophageal muscularis mucosae and uterus. Responses were also observed in the rat fundic strip and paced left atria. The guinea-pig urinary bladder, trachea, rat vas deferens and anococcygeus exhibited little or no response to endothelin at the concentrations studied (1 x 10 -2-3.2 x 10 -8M). Of the above preparations, the ileum and oesophageal muscularis mucosae were the most sensitive to endothelin (-log EC50 = 8.5 + 0.11 and 8.4 + 0.06, n = 6, respectively), exhibiting potencies similar to those observed in the endothelium-denuded aorta of the rat. 4 In competition-radioligand binding studies, endothelin did not displace either [3H]-PN 210-100 or [125I]< -)-co-conotoxin GVIA from binding sites in membranes from rat cerebral cortex and, skeletal muscle or from guinea-pig cerebral cortex and hippocampus, respectively. This indicates a lack of direct interaction of endothelin at the dihydropyridine binding site and the N-type calcium channel, respectively. However, in functional studies, contractile responses to endothelin (1 x 10-8M) in the endothelium-denuded aorta of the rat were potently reversed by nifedipine, verapamil, and prenylamine (-log IC50 values = 8.0 + 0.13, 7.2 + 0.09 and 6.6 + 0.08, n = 4-8,

show abstract

“…Yanagisawa et al (3) first showed that a calcium channel blocker, nicardipine, attenuated the vasoconstrictive responses to ET in rats, although the underlying mechanism has not yet been fully elucidated. Calcium channel blockers do not directly affect the ET receptors, but indirectly suppress ET-receptor-mediated signal-transduction resulting in abolition of the sustained increase in intracellular calcium concentrations caused by ET (19). Eventually, calcium channel blockers antagonize vascular effects of ET.…”

Section: Discussionmentioning

confidence: 99%

Effects of a Novel Dihydropyridine Derivative Calcium Channel Blocker, NKY-722, on Regional Hemodynamics, and Its Influences on the Effects of Endothelin in Anesthetized Rats.

et al. 1994

View full text Add to dashboard Cite

Regional vascular responses to NKY-722 (NKY), a novel dihydropyridine derivative calcium channel blocker, and the effects on the responses to endothelin (ET) were investigated using tracer microspheres with a reference sample method in anesthetized rats. Intravenous injections of NKY, 0.2 and 2mglkg, decreased blood pressure and total peripheral resistance dose-dependently. Cardiac index significantly increased only with the high dose regardless of bradycardia. Regional blood flow significantly changed with NKY: It increased in the brain, brown adipose tissue (BAT), intestine, colon and skin, but decreased in the liver, spleen, kidneys, adrenals and skeletal muscle. NKY decreased the regional vascular resistance in the brain, heart, lungs, BAT, intestine, colon and skin, but increased it in the liver, spleen and skeletal muscle. ET significantly increased blood pressure, but this was abolished by pretreatment with the low and high doses of NKY. Cardiac index became significantly lower with ET, and was not affected by NKY. Total peripheral resistance after ET remained lower with NKY pretreatments. ET decreased the blood flow mainly in the liver, spleen, kidneys, adrenals, BAT, intestine, colon, and skeletal muscle. Pretreatments with NKY prevented the decrease of flow caused by ET in the kidneys, adrenals, BAT, intestine, colon and skeletal muscle. These findings indicate that NKY lowers blood pressure mainly by decreasing the peripheral vascular resistance, and that NKY blunts many, but not all, endothelin effects on vasculature. (Hypertens Res 1994; 17: 29-34)

show abstract

Cellular mechanism of action by a novel vasoconstrictor endothelin in cultured rat vascular smooth muscle cells

Cited by 376 publications

References 6 publications

Specific receptors for endothelin‐3 in cultured bovine endothelial cells and its cellular mechanism of action

Specific receptors for endothelin‐3 in cultured bovine endothelial cells and its cellular mechanism of action

The pharmacological properties of the peptide, endothelin

Effects of a Novel Dihydropyridine Derivative Calcium Channel Blocker, NKY-722, on Regional Hemodynamics, and Its Influences on the Effects of Endothelin in Anesthetized Rats.

Contact Info

Product

Resources

About