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

12 d contractile activity via 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 DARA), which potently blocked both AT(1) and ET(A) receptors.

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

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

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

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

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

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

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

34 ETA receptor activation induces renal ER stress genes an

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

120 ]-2-sulfonamide derivatives as endothelin-A (ET(A)) receptor antagonists are described.

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

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

123 ETA receptor antagonists may prevent rebound pulmonary h

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

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

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

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

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

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

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

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

132 130/LIF receptor and ET-1/endothelin type A (ET(A)) receptor axis.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

148 -1 increases PWV, and this can be blunted by ET(A) receptor blockade.

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

150 ETA receptor blockade attenuated increases in macrophage

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

168 1 from vascular ECE-1 is sufficient to evoke ET(A) receptor-dependent constriction in retinal arterio

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

191 3 and (18)F-FBzBMS 5 bind selectively to the ETA receptor in vivo.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

225 ETA receptors predominate in the media of both normal an

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

227 92621 (25 mg/kg p.o.), but unaffected by the ET(A) receptor-selective antagonist SB 234551 (25 mg/kg

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

258 15q (TBC11251), binds competitively to human ETA receptors with a Ki of 0.43 +/- 0.03 nM and an IC50

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

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