ライフサイエンスコーパス: ET(A) receptor

1 ase to a molecular complex that included the ETA receptor.

2 ptake in 3T3-L1 adipocytes via activation of ETA receptor.

3 by A-216546, an antagonist selective for the ETA receptor.

4 tream signals triggered by activation of the ETA receptor.

5 ts, possessing subnanomolar affinity for the ETA receptor.

6 c hypertension through the activation of the ETA receptor.

7 llows cerebral hemorrhage via stimulation of ETA receptor.

8 e 1 and zymographic activity exclusively via ETA receptors.

9 us ET-1 modulates basal FHR, CBF and CVR via ETA receptors.

10 T plays a role in coronary tone mediated via ETA receptors.

11 d contractile activity via the endothelin A (ETA) receptor.

12 zyme-1 (ECE-1) and acts on the endothelin-A (ETA) receptor.

13 othelin antagonist, binds selectively to the ET(A) receptor.

14 ding affinity as well as selectivity for the ET(A) receptor.

15 ce of basal vascular tone acting through the ET(A) receptor.

16 tivation is initiated by Et-1 binding to the ET(A) receptor.

17 l/L, binds in a noncompetitive manner to the ET(A) receptor.

18 capacity while maintaining affinity for the ET(A)-receptor.

19 pe-selective binding to the A subtype of ET (ETA) receptors.

20 3) immortalized cells transiently expressing ET(A) receptors.

21 lly active dual antagonist of both AT(1) and ET(A) receptors.

22 ministration of BQ123, a specific blocker of ET(A) receptors.

23 of nociceptive fibers through activation of ET(A) receptors.

24 al vasculature and unmasked by inhibition of ET(A) receptors.

25 ntly through the activation of smooth muscle ET(A) receptors.

26 of endothelin-1 (ET) that activated pericyte ET(A) receptors.

27 DARA), which potently blocked both AT(1) and ET(A) receptors.

28 We conclude that gp130/LIF receptor and ET(A) receptor activation are essential for cardiac fibr

29 Taken together, these data suggest that ET(A) receptor activation in AngII-mediated hypertension

30 ET(A) receptor activation may contribute to the progress

31 CT-1 requires gp130/LIF receptor as well as ET(A) receptor activation.

32 constriction predominantly via smooth muscle ET(A) receptor activation.

33 ure causes increased plasma levels of ET and ET(A) receptor activation.

34 It is concluded that ETA receptor activation does not play a significant role

35 ETA receptor activation induces renal ER stress genes an

36 These observations indicate that ETA receptor activation mediates renal inflammation and

37 tive effects, mediating vasoconstriction via ETA receptor activation of vascular smooth muscle cells

38 ominal aortas, contractions to the selective ETA receptor agonist ET-1(1-31) were significantly incre

39 pe, because in contrast to ET-1, which is an ETA receptor agonist, ET-3 and Sarafotoxin-S6c, two ETB

40 ET-1 acting through ET(A) receptors altered pericyte currents and caused dep

41 tions in the binding of these antagonists to ETA receptors an, in the case of BMS-182874, also sugges

42 More recent studies have shown that the dual ET(A) receptor and angiotensin receptor blocker, sparsen

43 mpound exhibits low-nanomolar binding to the ETA receptor and a greater than 1000-fold selectivity ov

44 Moreover, the ETA receptor and downstream effector phospholipase C-bet

45 tection assay revealed significantly reduced ETA receptor and slightly raised ETB message levels in s

46 ice, which overcomes a reduced expression of ETA receptors and enables a selective increase in contra

47 tance arteries in diabetes via activation of ET(A) receptors, and ET(B) receptors provide vasculoprot

48 ich was inhibited by endothelial denudation, ET(A) receptor antagonism (BQ123), and ECE inhibition (p

49 lood flow response to exercise suggests that ET(A) receptor antagonism could be a therapeutic approac

50 These data indicate that ET(A) receptor antagonism could be a viable therapeutic

51 ET(A) receptor antagonism markedly increased leg blood f

52 This suggests that ET(A) receptor antagonism may have therapeutic potential

53 Taken together, these data suggest that ET(A) receptor antagonism may modify risk factors for ca

54 Oral, selective ET(A) receptor antagonism significantly reduced neointim

55 In conclusion, the combination of ETA receptor antagonism and ACE inhibition is synergisti

56 B receptors have differential roles in CFVs: ETA receptor antagonism and ETB receptor stimulation red

57 gies in SCD mice, and suggest that long-term ETA receptor antagonism may provide a strategy for the p

58 bition was comparable to that measured after ETA receptor antagonism with BQ-123 injection.

59 rats were used in the presence or absence of ETA receptor antagonism.

60 Animal studies suggest that endothelin A (ETA) receptor antagonism and angiotensin-converting enzy

61 The ET(A) receptor antagonist (2) (N-(3,4-dimethyl-5-isoxazo

62 structural elements in a biphenylsulfonamide ET(A) receptor antagonist (2) followed by additional opt

63 ET-1 (2 and 6 pmol/min); BQ-123, a selective ET(A) receptor antagonist (3 and 10 nmol/min); and BQ-78

64 ting our hypothesis that the combined use of ET(A) receptor antagonist (ABT-627; Atrasentan) with Tax

65 through ET(A) receptors, because a specific ET(A) receptor antagonist (BQ610) blocked these effects

66 Furthermore, the selective ET(A) receptor antagonist ambrisentan attenuated the inc

67 In the outer medulla, both the ET(A) receptor antagonist and triple therapy reduced the

68 mized in a double-blind manner to either the ET(A) receptor antagonist atrasentan (10 mg) or placebo

69 oto-Kakizaki (GK) rats treated with vehicle, ET(A) receptor antagonist atrasentan (5 mg x kg(-1) x da

70 er a 60-minute intracoronary infusion of the ET(A) receptor antagonist BQ-123.

71 ET-1-induced responses were inhibited by the ET(A) receptor antagonist BQ123 and the phospholipase C

72 ET(A) receptor antagonist BQ123 inhibited most (approxim

73 Et-1-induced IL-8 production was blocked by ET(A) receptor antagonist BQ610, but not by ET(B) recept

74 e Ad.ET-1 group, intravenous infusion of the ET(A) receptor antagonist FR 139317 reduced the blood pr

75 ion is therefore amenable to reversal by the ET(A) receptor antagonist FR139317, and this model may o

76 Mice treated concomitantly with the ET(A) receptor antagonist had lower BP and fewer CD3(+)

77 We have previously disclosed the selective ET(A) receptor antagonist N-(3,4-dimethyl-5-isoxazolyl)-

78 roteinuric CKD to compare the effects of the ET(A) receptor antagonist sitaxentan, nifedipine, and pl

79 n patients with HF, we infused the selective ET(A) receptor antagonist sitaxsentan at increasing rate

80 In a preliminary PAH study, the selective ET(A) receptor antagonist sitaxsentan improved six-min w

81 Treatment with the selective ET(A) receptor antagonist sitaxsentan, orally once daily

82 ocked effects of ET-1 and sarafotoxin 6c; an ET(A) receptor antagonist was without effect.

83 dy, we show that HJP-272, a highly selective ET(A) receptor antagonist with an IC(50) of 70.1 nmol/L,

84 uring exercise with either saline or BQ-123 (ET(A) receptor antagonist) infusion following a 2-week w

85 d DOCA-salt rats was reversed by a selective ET(A) receptor antagonist, ABT-627, the flavoprotein inh

86 e studied the effects of BQ 123, a selective ET(A) receptor antagonist, after ligation of the ductus

87 (-1)) was administered in the presence of an ET(A) receptor antagonist, BQ-123 (1 mg/kg).

88 emia, we determined the effect of a specific ET(A) receptor antagonist, BQ123 (1mg/kg, intravenously

89 The specific ET(A) receptor antagonist, BQ123, significantly inhibite

90 A specific ET(A) receptor antagonist, BQ123, was infused (40 nmol/m

91 by ET-1 was prevented by BQ-123, a selective ET(A) receptor antagonist, but was not affected by pertu

92 odynamic effects of sitaxsentan, a selective ET(A) receptor antagonist, in patients with chronic stab

93 line, AngII infusion, AngII infusion with an ET(A) receptor antagonist, or AngII infusion with triple

94 d this increase was blocked with a selective ET(A) receptor antagonist.

95 vious exposure of cells to the endothelin-A (ET(A)) receptor antagonist BQ-123 (1 microm) prevented E

96 .001), whereas infusion of the endothelin-A (ET(A)) receptor antagonist BQ-123 significantly reduced

97 ium nitroprusside and the endothelin type A (ET(A)) receptor antagonist BQ-123 were assessed using ve

98 The endothelin-A (ET(A)) receptor antagonist FR139317 (3 or 30 nmol) injec

99 at long-term treatment with an endothelin-A (ET(A)) receptor antagonist improves coronary endothelial

100 optimal dose of the selective endothelin A (ET(A)) receptor antagonist sitaxsentan for the treatment

101 was strongly inhibited by the endothelin-A (ET(A)) receptor antagonist, BQ-123 (3.2 m).

102 gonist, BQ-788, but not by the endothelin A (ET(A)) receptor antagonist, BQ-123, consistent with pred

103 during HPP (n=7), isch kidneys receiving the ETA receptor antagonist (n=7), and isch kidneys receivin

104 concomitant administration of the selective ETA receptor antagonist (PD 156707 24 mg/d), and sham co

105 Therefore, although the ETA receptor antagonist A-127722 can inhibit ETA-mediate

106 rteries of DOCA-salt rats with the selective ETA receptor antagonist ABT-627, NADPH oxidase inhibitor

107 Cotreatment with the ETA receptor antagonist BQ 610 prevented these effects,

108 ne study, six subjects received placebo, the ETA receptor antagonist BQ-123 alone, and BQ-123 in comb

109 ET1 effects on [Ca2+]i were prevented by the ETA receptor antagonist BQ123 (cyclo-D-Asp-Pro-D-Val-Leu

110 y vasoconstriction, which was blocked by the ETA receptor antagonist PD 156707 (n=3).

111 tral endopeptidase inhibitor) and BQ-123 (an ETA receptor antagonist) increased FBF by 52 +/- 10% (P

112 n, either saline (negative control), BQ-123 (ETA receptor antagonist, 10 microg/min), BQ-788 (ETB rec

113 vels and that pretreatment with PD156707, an ETA receptor antagonist, blocks the rebound hypertension

114 bation of coronary segments with a selective ETA receptor antagonist, BQ485 (1 mumol/L), had no effec

115 BQ-123, an ETA receptor antagonist, but not saralasin, an angiotens

116 osure to either BQ123 (10 microM), selective ETA receptor antagonist, U73122 (5 microM), or SKF 96365

117 intravitreous injections of ET-1; BQ-123, an ETA receptor antagonist; and phosporamindon, an endothel

118 very of a potent and selective endothelin A (ETA) receptor antagonist for the potential treatment of

119 ith the infusion of either the endothelin-A (ETA) receptor antagonist FR139317, or saline vehicle.

120 Effect of ETA-receptor antagonist, BQ123, on postischemic hypoperf

121 with longer duration than DARA 3 or AT(1) or ET(A) receptor antagonists alone.

122 Therefore, ET(A) receptor antagonists did not bind directly to opio

123 These findings indicate that ET(A) receptor antagonists potentiate morphine antinocic

124 Mechanism of interaction of ET(A) receptor antagonists with morphine was investigate

125 present study, we investigated the effect of ET(A) receptor antagonists, BQ123 and BMS182874, on morp

126 ]-2-sulfonamide derivatives as endothelin-A (ET(A)) receptor antagonists are described.

127 H compound of our series of novel synthetic (ET(A)) receptor antagonists.

128 ECE inhibitors and ETA receptor antagonists may be useful as vasodilator ag

129 ETA receptor antagonists may prevent rebound pulmonary h

130 f two moderately potent series of nonpeptide ETA receptor antagonists.

131 ides are potent and selective small molecule ETA receptor antagonists.

132 results indicate that in adult mice cardiac ET(A) receptors are not necessary for either baseline ca

133 the docked conformation of BMS-182874 in the ETA receptor are proposed as a starting point for furthe

134 The data suggest that ETA receptors are negatively coupled to L-type Ca2+ chan

135 TM cells expressed mRNA of ET(A) receptors as detected by QPCR, whereas the ET(B) m

136 These results highlight targeting the ETA receptor as a therapeutic approach against ER stress

137 y CT-1 and that there is synergism with ET-1/ET(A) receptor axis.

138 130/LIF receptor and ET-1/endothelin type A (ET(A)) receptor axis.

139 onstriction, possibly through effects on the ET(A) receptor, because selective ET(B) receptor-induced

140 ET-1-mediated effects were generated through ET(A) receptors, because a specific ET(A) receptor antag

141 A consistent decrease in ETA receptor binding sites was noted primarily within th

142 r, we describe how a pharmacophore model for ETA receptor binding was developed which enabled these t

143 CHF/ET(A)-Low Dose: pacing for 2 weeks then ET(A) receptor blockade (BMS 193884, 12.5 mg/kg, b.i.d.)

144 CHF/ET(A)-High Dose: paced for 2 weeks then ET(A) receptor blockade (BMS 193884, 50 mg/kg, b.i.d.) f

145 f this study was to test the hypothesis that ET(A) receptor blockade attenuates superoxide production

146 Selective ET(A) receptor blockade caused local pulmonary vasodilat

147 ailure receiving conventional therapy, acute ET(A) receptor blockade caused selective pulmonary vasod

148 In summary, chronic intrauterine ET(A) receptor blockade decreased PAP in utero, decrease

149 nner, demonstrating the synergy of AT(1) and ET(A) receptor blockade in a single molecule.

150 rtensive patients, the vasodilator effect of ET(A) receptor blockade was significantly higher in blac

151 twofold with CHF and remained increased with ET(A) receptor blockade.

152 this response is sensitive to ET(B) but not ET(A) receptor blockade.

153 in HG rats, and this effect was prevented by ET(A) receptor blockade.

154 -1 increases PWV, and this can be blunted by ET(A) receptor blockade.

155 fy the effects of endothelin (ET) subtype-A (ET(A))) receptor blockade during the development of cong

156 ETA receptor blockade attenuated increases in macrophage

157 rting enzyme (ECE) inhibition and endothelin ETA receptor blockade in CHF patients treated with ACE i

158 Thus, specific ETA receptor blockade may provide a new and useful thera

159 thiorphan and its absence during concomitant ETA receptor blockade suggest that it is mediated by end

160 In a separate group of rats, ETA receptor blockade was verified after 3 d of drinking

161 study was to determine the effect of chronic ETA receptor blockade, using the orally active antagonis

162 d to control levels with RVP and concomitant ETA receptor blockade.

163 F) responses to intraarterial infusion of an ET(A) receptor blocker (BQ-123) were analyzed by plethys

164 The insulin and the endothelin type A (ETA) receptor both can couple into the heterotrimeric G

165 aarterial infusion of a selective blocker of ET(A) receptors (BQ-123) and, on a different occasion, t

166 -arterial infusion of a selective blocker of ETA receptors (BQ-123) and, on a separate occasion, to E

167 migration was unaffected by the blockade of ETA receptor, but it was inhibited by ETB receptor antag

168 In obese subjects, antagonism of ETA receptors by BQ-123 increased forearm flow during sa

169 ion of interactions that underlie antagonist-ETA receptor complex formation.

170 Thus, ET-1 acting via the ET(A) receptor contributes to basal human coronary vasoc

171 Thus, ET-1, acting through the ET(A) receptors, contributes to the control of blood pre

172 ting ET-1 interaction with its endothelin A (ET(A)) receptor could be useful for inhibiting prostate

173 al arch expression of goosecoid is absent in ETA receptor-deficient mice, placing the transcription f

174 ET(A) receptor density was comparable in right and left

175 1 from vascular ECE-1 is sufficient to evoke ET(A) receptor-dependent constriction in retinal arterio

176 f CBF and CVR persists during hypoxaemia but ETA receptors do not appear to contribute to the decreas

177 y reflecting overactivity of this system and ET(A) receptor downregulation.

178 In cells overexpressing ET(B), but not ET(A) receptors, ET-1 increased Na/H antiporter activity

179 atrix-associated gene expression through the ETA receptor (ETAR) and promotes fibroblast differentiat

180 These results indicate that stimulation of ET(A) receptors evokes PKC-dependent TRPC1 channel activ

181 rbated in the absence of COX-2 with enhanced ET(A) receptor expression and increased PASMC hypertroph

182 resulted in PASMC hypertrophy and increased ET(A) receptor expression in pulmonary arterioles.

183 ptors was decreased in MCT(sl/sl) rat lungs, ET(A) receptor expression increased.

184 antisense oligodeoxynucleotide to attenuate ET(A) receptor expression on nociceptors attenuated ET-1

185 tion of matrix remodeling was dependent upon ETA receptor expression and was blocked by specific inhi

186 To determine whether ET-1, via the ET(A) receptor, facilitates T cell infiltration in the k

187 expression, is initiated by Et-1 binding to ET(A) receptor followed by subsequent activation of prot

188 g to its cognate receptor, the endothelin A (ET(A)) receptor, found on ectomesenchymal cells.

189 gonists (ERAs) that target the endothelin A (ET(A)) receptor have demonstrated benefits in animal mod

190 Endothelin receptors, particularly the ET(A) receptor, have been shown to participate in the pa

191 ly selective antagonist of the endothelin-A (ET(A)) receptor; however, its peptidic nature leads to p

192 o induce any change in the expression of the ET(A) receptor in both NTM and GTM cells, and this was s

193 at ET-1 stimulates leptin production via the ET(A) receptor in cultured adipocytes.

194 ression of preproendothelin-1 (ET-1) and its ET(A) receptor in the kidney was higher in eNOS-deficien

195 Since ET(A) receptors in the central nervous system (CNS) are

196 und that beta-arrestin 1 associated with the ETA receptor in an agonist-dependent manner and that bet

197 opment of these radioligands for imaging the ETA receptor in humans is warranted.

198 the importance of exclusively targeting the ETA receptor in SCD.

199 3 and (18)F-FBzBMS 5 bind selectively to the ETA receptor in vivo.

200 al and clinical investigation of the role of ETA receptors in diseases.

201 f endothelin-1, acting through endothelin A (ET(A) ) receptors, in modulating the central and periphe

202 We hypothesized that ET(A) receptor inhibition would improve human coronary v

203 al), we infused BQ-123, an antagonist of the ET(A) receptor, into a major coronary artery (infused ar

204 ly by the ET(A) antagonist BQ610, suggesting ET(A) receptor involvement.

205 ng during crest cell development because the ET(A) receptor is an intracellular signaling molecule.

206 The activity of endogenous ET-1 on ET(A) receptors is enhanced in the resistance vessels of

207 The ETA receptor is a seven-transmembrane G-protein-coupled

208 The endothelin subtype-A (ETA) receptor is a member of a family of G-protein-coupl

209 As endothelin binds to ET(A) receptors, it stimulates vascular smooth muscle ce

210 superior affinity, high selectivity for the ETA receptor (Ki, 0.46 nM for ETA and 13000 nM for ETB),

211 ptimization of in vitro activity against the ETA receptor led to the discovery of (R)-4-[2-cyano-5-(3

212 n of nociceptors, both through activation of ET(A) receptors likely on nociceptive terminals.

213 dial ischaemia through direct stimulation of ET(A) receptors likely to be located in the cardiac sens

214 Such an effect on the ET(A) receptor may relate to the antianginal properties

215 Therefore, drugs that block ET(A) receptors may be effective in reducing large arter

216 ion of ET-1 and the subsequent activation of ETA, receptor may play an important role in hematoma-ind

217 This derivative inhibited the ETA receptor mediated release of arachidonic acid from r

218 ET(A) receptor-mediated TRPC1 channel activity was selec

219 d nitric oxide activity and basal endogenous ET(A) receptor-mediated vascular tone.

220 rate that the algogenic peptide ET-1 induces ET(A) receptor-mediated, hyperpolarizing shifts in the v

221 (eNOS(-/-)) mice, influences endothelin (ET) ETA receptor-mediated smooth muscle contraction and, if

222 sociated with inhaled NO therapy may involve ETA receptor-mediated superoxide production.

223 We show that ETA receptor mRNA is expressed by the neural crest-deriv

224 ETB receptors (predominantly ETA), but that ETA receptor mRNA levels and ETA binding sites on fibrob

225 The levels of ETA receptor mRNA were elevated 29.3-fold (P < .001) and

226 curred slightly earlier than the increase in ETA receptor mRNA, showing 15.1-fold increase at 1 day (

227 -fold in Tyr129Ala, Tyr129Ser, and Tyr129His ETA receptor mutants.

228 er pain through its actions on endothelin-A (ET(A)) receptors of local nociceptors, it can coincident

229 ET(A) receptors on vascular smooth muscle cells mediate

230 Targeted deletion of the ET(A) receptor or its ligand endothelin-1 (ET-1) causes

231 enhances myocyte contractility by activating ETA receptor-phospholipase C-beta 1-PKC-epsilon signalin

232 ET-1 levels and subsequent activation of the ETA receptor play a direct and contributory role in the

233 macokinetic profile as well as the AT(1) and ET(A) receptor potency of 3.

234 ETA receptors predominate in the media of both normal an

235 tudies, a selective antagonist of endothelin ET(A) receptors, SB 234551, improved neurological and hi

236 92621 (25 mg/kg p.o.), but unaffected by the ET(A) receptor-selective antagonist SB 234551 (25 mg/kg

237 n = 30) were injected intravitreally with an ETA receptor-selective antagonist, BQ-123, and an inhibi

238 se analogues retained equivalent or improved ETA receptor selectivity and antagonist potency, versus

239 ET-1/ET(A) receptor signaling evoked a 7.4-fold increase in c

240 Furthermore, in vivo blockade of ET(A) receptors significantly reduced arterial superoxid

241 Selective blockade of the ETA receptor significantly reduced expression of the mat

242 We conclude that ET(A) receptor stimulation contributes to the pathogenes

243 ables a selective increase in contraction to ETA receptor stimulation.

244 on of the inositol phosphate pathway via the ET(A) receptor subtype but does not couple to inhibition

245 und 10b with subnanomolar affinity for human ETA receptor subtype and with an ETB/ETA activity ratio

246 In addition, BQ 610, an ETA receptor subtype antagonist, inhibited ET-1-induced

247 hese effects were mediated by the endothelin ETA receptor subtype because at ETB receptor-selective a

248 ET-1 binds to the ETA receptor subtype to activate phospholipase A2 and to

249 on cAMP accumulation is mediated through the ETA receptor subtype, because in contrast to ET-1, which

250 LC and increased [Ca2+]i in HCM calls by the ETA receptor subtype.

251 These results indicate that signaling of ET(A) receptors through the G(i/o) pathway in lactotroph

252 nner, but did not inhibit the ability of the ET(A) receptor to activate ERK.

253 ) Galpha(q/11) can transmit signals from the ET(A) receptor to the p110alpha subunit of PI 3-kinase,

254 ransient cross-coupling of Ca(2+)-mobilizing ET(A) receptors to the G(i)/G(o) pathway in somatotrophs

255 Src kinase form a molecular complex with the ETA receptor to mediate ET-1 signaling to Galpha(q/11) w

256 nM and with a 2000-fold selectivity for the ETA receptor versus the ETB receptor.

257 The ET(A) receptor was also elevated in infected arteries.

258 The ET(A) receptor was linked to calcium mobilization as ET-

259 Expression of ET(A) receptors was significantly increased following ce

260 s demonstrated that the aortic expression of ETA receptors was decreased in eNOS(-/-) compared with W

261 chemical staining approach, we observed that ET(A) receptors were expressed in cardiac sensory neuron

262 Further, the protein levels of ETA receptor were also increased in the PVN of E2 treate

263 In arteries with early and late disease, ETA receptors were localized to medial smooth muscle but

264 xpressed approximately 560,000 sites/cell of ETA receptor, which was not altered during differentiati

265 binding of endothelin-1 to the endothelin-A (ET(A)) receptor with either BQ-123 or with HJP-272, the

266 This compound binds to the ETA receptor with an affinity (Ki) of 0.034 nM and with

267 15q (TBC11251), binds competitively to human ETA receptors with a Ki of 0.43 +/- 0.03 nM and an IC50

268 nhibition of ET-1 radioligand binding at the ET(A) receptor, with a 1000-fold selectivity for the ET(

269 the hypothesis that chronic blockade of the ETA receptor would have direct and beneficial effects on