ライフサイエンスコーパス: TXA2

1 ored microcirculatory blood flow and reduced TXA2 .

2 achidonic acid to synthesize thromboxane A2 (TxA2).

3 mportant agonists, including thromboxane A2 (TXA2).

4 vasoconstricting prostanoid thromboxane A2 (TXA2).

5 istinct eicosanoids, such as thromboxane A2 (TXA2).

6 mmatory drugs (NSAIDs), inhibit PGI2 but not TxA2.

7 vivo and specifically limits the response to TxA2.

8 th a concomitant rise in the vasoconstrictor TxA2.

9 creted their granular contents nor generated TXA2.

10 81067, without affecting the contribution of TXA2.

11 abolished the mitogenic effects of 5-HT and TXA2.

12 membrane receptors transduce the effects of TxA2.

13 esion coincident with augmented formation of TxA2.

14 orresponding increase in the biosynthesis of TxA2.

15 a mechanism independent of platelet-derived TXA2.

16 ote inflammation and restrain the effects of TxA2.

17 Furthermore, it catalyzed formation of TXA2, 12-hydroxy-5,8,10-heptadecatrienoic acid, and malo

18 inary excretion of major metabolites of both TxA2, 2,3-dinor TxB2 (Tx-M), and PGI2, 2,3-dinor 6-keto

19 rome P450 enzyme catalyzing the synthesis of TxA2, a potent modulator of vascular smooth muscle contr

20 Prior treatment with the TxA2 agonist U46619 reduced subsequent U46619-induced in

21 was no difference in the contraction by the TXA2 agonist U46619, or TP receptor expression in arteri

22 A TXA2 agonist, U46619, reconstitutes both migration and a

23 platelets do not aggregate after exposure to TXA2 agonists.

24 Thrombin and TXA2 also synergized with P2Y12 in the absence of antico

25 ry wave of platelet aggregation induced by a TXA2 analog and thrombin receptor-activating peptides th

26 Supplementing a TXA2 analog, U46619, corrected the defect of LIMK1(-/-)

27 , we present a novel finding that the stable TXA2 analogue, U46619, induces two waves of platelet sec

28 Here, we demonstrate that TxA2 and ADP are required for collagen-induced platelet

29 ore, a high level of collagen can cause weak TxA2 and ADP-independent aggregation, but maximal aggreg

30 g disorder and altered vascular responses to TXA2 and arachidonic acid.

31 and enhances production of bioactive lipids (TXA2 and isoprostanes) which act through the thromboxane

32 The systemic biosynthesis of TxA2 and prostacyclin was assessed by analysis of their

33 had nearly complete (99.7%) loss of platelet TXA2 and significantly suppressed levels of macrophage a

34 tal muscle of the hindlimb are stimulated by TxA2 and that the release of TxA2 in skeletal muscle cou

35 PLCgamma2 phosphorylation is potentiated by TxA2 and that TxA2 plays a critical role in the most pro

36 t ridogrel abolished the mitogenic effect of TXA2 and the interaction between 5-HT and TXA2 without a

37 re not significantly different between C-His-TxA2 and wt-TxA2 receptors.

38 oconstrictor prostaglandins, thromboxane A2 (TXA2 ) and prostaglandin F2alpha (PGF2alpha ), on skin m

39 secondary mediators such as thromboxane A2 (TxA2) and ADP, which are agonists for G-protein-coupled

40 osphate (ATP) secretion in a thromboxane A2 (TxA2)- and Ca2+-dependent manner.

41 elease of secondary agonists such as ADP and TxA2, and 4) can be initiated by at least some members o

42 ion after FPI was observed with SQ 29,548, a TXA2 antagonist.

43 nces in PVAT function in which PGF2alpha and TXA2 antagonists can inhibit the PVAT-induced vasoconstr

44 est that most of the recognized functions of TXA2 are mediated by the single known Tp gene locus.

45 These findings identify TXA2 as a COX-2 product that functions as a critical int

46 Although the number of TxA2 binding sites decreased in TxA2R-P cells after prol

47 Affinity and specificity of TxA2 binding to the mutant receptor were identical to wi

48 g, both conditions associated with increased TxA2 biosynthesis.

49 et significantly impaired PORH and increased TXA2 but did not change PGF2alpha levels.

50 dense granules and generate thromboxane A2 (TXA2), but platelets adhering to acid soluble monomeric

51 xane A2 (TXA2), we examined whether 5-HT and TXA2 can induce SMC proliferation and whether there is s

52 rictive prostanoids, such as thromboxane A2 (TXA2 ), contributes to endothelial dysfunction and incre

53 Despite a failure to suppress TxA2-dependant platelet aggregation, celecoxib had a mod

54 d elicits ATP secretion in a thromboxane A2 (TxA2)-dependent manner.

55 , but not celecoxib, significantly inhibited TxA2-dependent aggregation, induced ex vivo by arachidon

56 K members, Lyn or Fyn, were defective in the TXA2-dependent second wave of platelet aggregation induc

57 dition to their recognized roles in ADP- and TXA2-dependent secondary amplification pathways.

58 PGI2]) and vasoconstricting (thromboxane A2 [TxA2]) eicosanoids may be important in preeclampsia, but

59 The mitogenic effects of 5-HT and TXA2 either alone or in combination was examined in seru

60 Finally, platelet-derived-TxA2 elicits a full neutrophil response by inducing the

61 TxA2 exerts its effects through a membrane receptor (TP)

62 fords cardioprotection through inhibition of TxA2 formation by platelet cyclooxygenase (COX-1).

63 st that GPVI is directly associated with the TXA2 generating system during platelet-collagen interact

64 a phospholipase C inhibitor, also abolished TXA2 generation and Erk phosphorylation.

65 The COX-2-dependent increase in TxA2 generation augments cardiac hypertrophy, whereas fo

66 Furthermore, inhibition of 2-MeSADP-induced TxA2 generation by fibrinogen receptor antagonist was no

67 With the other antibodies, TXA2 generation corresponded with the amount of adhesion

68 P2Y receptors that contribute to ADP-induced TXA2 generation have not been clearly delineated.

69 In addition, TxA2 generation induced by co-stimulation of Gi and Gz p

70 ADP-induced TXA2 generation requires the costimulation of P2Y1, P2Y1

71 ependent adhesion, they completely inhibited TXA2 generation under both divalent cation-dependent and

72 ve dysfunctional GIRK2 subunits, ADP-induced TXA2 generation was impaired.

73 hways, and both 2-MeSADP- and AYPGKF-induced TxA2 generation was significantly diminished in Pyk2-def

74 tin polymerization inhibitors did not reduce TXA2 generation, but rather accelerated platelet aggrega

75 ther GIRK subunits contribute to ADP-induced TXA2 generation, via the regulation of the Src and cPLA2

76 ion of ADP-induced cPLA2 phosphorylation and TXA2 generation, without affecting the conversion of AA

77 ys can substitute for integrin signaling for TxA2 generation.

78 2 receptor, in the regulation of ADP-induced TXA2 generation.

79 d 2MeSADP-mediated cPLA2 phosphorylation and TXA2 generation.

80 an absolute requirement for Src/Erk-mediated TXA2 generation.

81 ADP-, but not thrombin-induced thromboxane (TxA2) generation depends on integrin signaling.

82 because granular secretion, Thromboxane A2 (TxA2) generation, as well as fibrinogen receptor activat

83 d malondialdehyde (MDA) at a ratio of 1:1:1 (TXA2:heptadecatrienoic acid:MDA).

84 ride) and inflammatory cytokines (especially TxA2, IL-1 beta, PGE2, and TNF-alpha) which serve to ini

85 e stimulated by TxA2 and that the release of TxA2 in skeletal muscle could evoke cardiorespiratory re

86 contributes to the increased biosynthesis of TxA2 in smokers, most likely from inflammatory cells.

87 We addressed this issue and the role of TxA2 in the promotion and regression of diffuse, establi

88 complement released PGE2 and thromboxane A2 (TXA2), in addition to increased amounts of PGI2.

89 nosine diphosphate (ADP), or thromboxane A2 (TXA2), in addition to their recognized roles in ADP- and

90 n kinase C (PKC) or cAMP-dependent kinase on TxA2-induced [Ca2+]i mobilization was measured.

91 ild type receptors, but had little effect on TxA2-induced desensitization of mutant receptors.

92 Protein kinase C (PKC) inhibitors attenuated TxA2-induced desensitization of wild type receptors, but

93 In contrast, TxA2-induced inositol trisphosphate generation by the mu

94 TXA2 induces vasoconstriction by way of activation of th

95 peripheral vascular beds in the rat and that TXA2 is a major prostanoid formed in the normal rat lung

96 Thromboxane A2 (TXA2) is a labile metabolite of arachidonic acid that ha

97 Thromboxane A2 (TXA2) is a potent inducer of vasoconstriction and platel

98 Thromboxane A2 (TxA2) is a potent vasoconstrictor and platelet agonist.

99 Here, we show that thromboxane A2 (TXA2) is one of several eicosanoid products generated by

100 By contrast, celecoxib decreased TXA2 levels but had no significant effects on blood flow

101 enic response in tissues exposed to elevated TXA2 levels in which revascularization is important.

102 OX-1 and -2) and prostaglandins and at least TXA2, may mediate the drugs cardiovascular effects.

103 Thromboxane A2 (TXA2)-mediated platelet secretion and aggregation are im

104 ession of thromboxane (TX) A2 production and TXA2-mediated platelet activation and aggregation.

105 odel for the prevention and treatment of the TXA2-mediated thrombosis involved in strokes and myocard

106 t phenylephrine stimulated production of the TXA2 metabolite TXB2, which was increased in eNOS(-/-) c

107 ssium, plasma concentrations of TXB2 (stable TXA2 metabolite) and PGF2alpha , soluble cell adhesion m

108 suppressed levels of macrophage and urinary TXA2 metabolites.

109 We report here that the TXA2 mimetic [1S-(1alpha, 2beta(5Z), 3alpha(1E, 3R), 4al

110 The initial concentration of the TxA2 mimetic IBOP required to reduce peak intracellular

111 whereas the effect of TXA2 (U46619, a stable TXA2 mimetic) on inducing proliferation of SMCs was obse

112 U46619, a PGH2/TxA2 mimetic, induced specific phosphorylation of both i

113 R-P cells after prolonged stimulation with a TxA2 mimetic, those in the TxA2R-E cells increased marke

114 ere designed to test the hypothesis that the TxA2 mimetic, U46,619, would stimulate group III and IV

115 :1 and a specific activity of 12 micromol of TXA2/min/mg of protein at 23 degreesC.

116 of 5-HT and its synergistic interaction with TXA2 on SMC proliferation was abolished by a 5-HT2 recep

117 esize prostaglandin E2 (PGE2) PGI2 > PGF2a > TxA2, only PGI2 enhanced RMIC viability following hypert

118 n, without affecting the conversion of AA to TXA2 or ADP-induced primary platelet aggregation in aspi

119 the rate of catalytic conversion of PGH2 to TXA2 or MDA was at least 15,000 s(-1) and the lower limi

120 induced by a high level of collagen requires TxA2 or secretion.

121 omerization reaction to form thromboxane A2 (TXA2) or a fragmentation reaction to form 12-l-hydroxy-5

122 preferential inhibition of platelet-derived TXA2 over protective vascular-derived prostacyclin (PGI2

123 nder shear stress that is independent of the TXA2 pathway.

124 sphorylation is potentiated by TxA2 and that TxA2 plays a critical role in the most proximal event of

125 Thromboxane A2 (TXA2) potently stimulates platelet aggregation and smoot

126 these conditions to enable thrombin-induced TxA2 production and adenosine diphosphate secretion, nec

127 ling is required, at least in part, for this TxA2 production and ADP secretion.

128 r both bt/VWF-mediated agglutination-induced TxA2 production and GPIb-dependent stable arterial throm

129 Because most trials using aspirin to reduce TxA2 production have failed to prevent preeclampsia, it

130 ated by GPIb-mediated agglutination to cause TxA2 production have not been identified.

131 GPIb-mediated agglutination that results in TxA2 production is dependent on Bruton tyrosine kinase (

132 e that bt/VWF-mediated agglutination-induced TxA2 production is dependent on signaling apparently ini

133 This agglutination-elicited TxA2 production occurs in the absence of ATP secretion.

134 not to be required for agglutination-driven TxA2 production or activation of alphaIIbbeta3, but were

135 The signaling that results in TxA2 production was shown to be initiated by Lyn, enhanc

136 gen-induced platelet signaling, the roles of TxA2 production, adenosine diphosphate (ADP) and dense-g

137 ression and PGI2 synthesis, had no effect on TXA2 production, and decreased cell numbers by 50%, indi

138 Selective COX-2 antagonists inhibit TXA2 production, endothelial migration, and fibroblast g

139 t reduced PGI2 production, but not increased TxA2 production, occurs many months before clinical onse

140 ated by GPIb-mediated agglutination to cause TxA2 production.

141 signaling, granule release, thromboxane A2 (TxA2) production, and aggregation.

142 se A2 (cPLA2) and consequent thromboxane A2 (TXA2) production.

143 nds, including COX-1 (but not COX-2)-derived TxA2, promote initiation and early progression of athero

144 -2 (COX-2) (indomethacin or celecoxib) or of TXA2/prostaglandin H2 receptors (SQ-29548).

145 ism of purinergic receptors (suramin+RB2) or TXA2 receptor (SQ29548), or by intratracheal apyrase.

146 r thromboxane A2 (TxA2), we created a mutant TxA2 receptor (TP receptor) in which serines at position

147 Human EC express both TXA2 receptor (TP) isoforms; however, the effects of ind

148 pressed in mice genetically deficient in the TxA2 receptor (TP) or treated with a TP antagonist.

149 Deletion of the TxA2 receptor (TP) reduces the hyperplastic response to

150 The TXA2 receptor (TXA2R) is a member of the G protein-coupl

151 ligand and immunoaffinity chromatography, 2) TXA2 receptor activation stimulates GTPgammaS binding to

152 separate experiments, it was found that the TXA2 receptor agonist U46619 stimulated [35S]guanosine 5

153 ed as potent dual-acting agents to block the TXA2 receptor and to inhibit the thromboxane synthase (T

154 pecifically blocked by pretreatment with the TXA2 receptor antagonist, BM13.505.

155 al angiogenesis are similarly inhibited by a TXA2 receptor antagonist, SQ29548.

156 o Galpha13, and 3) Galpha13 affinity for the TXA2 receptor can be modulated by agonist-receptor activ

157 The requirement for Btk and TxA2 receptor function in GPIb-dependent arterial thromb

158 aphy using an antibody raised against native TXA2 receptor protein.

159 irect evidence that endogenous Galpha13 is a TXA2 receptor-coupled G-protein, as: 1) its alpha-subuni

160 sphorylation of the carboxyl terminus of the TXA2 receptor.

161 ng to the third intracytoplasmic loop of the TXA2 receptor.

162 S18886 is an orally active thromboxane A2 (TXA2) receptor (TP) antagonist in clinical development f

163 Two subtypes of the thromboxane A2 (TxA2) receptor (TxA2R-E and TxA2R-P), which differ in th

164 upled agonist receptors, the thromboxane A2 (TXA2) receptor, and protease-activated receptors (PARs).

165 to purify the human platelet thromboxane A2 (TXA2) receptor-Galphaq complex.

166 Endothelial cells express TXA2 receptors (TP) but the effects of TP stimulation on

167 ation of a high level of expression of C-His-TxA2 receptors and a rapid purification procedure follow

168 haq and Galpha13 are functionally coupled to TXA2 receptors and dissociate upon agonist activation.

169 (C-His) was ligated to the alpha-isoform of TxA2 receptors and expressed in COS-7 and Chinese hamste

170 These data identify TXA2 receptors as cGMP-dependent protein kinase substrat

171 The C-His-TxA2 receptors bound the radioligands 125I-7-[(1R,2S,3S,

172 affinity methods, in vivo phosphorylation of TXA2 receptors by cyclic GMP was demonstrated from 32P-l

173 that in addition to Galphaq, purification of TXA2 receptors by ligand (SQ31,491)-affinity chromatogra

174 de mapping studies of in vivo phosphorylated TXA2 receptors demonstrated cGMP mediates phosphorylatio

175 let inhibition by NO, activation of platelet TXA2 receptors in the presence of cGMP was studied.

176 vitro, but not Galphaq copurifying with the TXA2 receptors in these experiments.

177 to catalyze the phosphorylation of platelet TXA2 receptors in vitro, but not Galphaq copurifying wit

178 he relationship of structure to function for TxA2 receptors is limited because of their low levels of

179 r evidence for functional coupling of G13 to TXA2 receptors was provided in studies where solubilized

180 lets deficient in PLC gamma 2, G alpha q, or TxA2 receptors, as well as platelets treated with a prot

181 y another G-protein associated with platelet TXA2 receptors.

182 ssion (Bmax = 95 +/- 6 pmol/mg) of the C-His-TxA2 receptors.

183 y different from those of the wild type (wt)-TxA2 receptors.

184 ficantly different between C-His-TxA2 and wt-TxA2 receptors.

185 ased structure-function and other studies of TxA2 receptors.

186 Thromboxane A2 (TxA2) receptors belong to the class of G-protein-coupled

187 Gi-, and COX1-dependent autocrine/paracrine TXA2 release and consequent TP activation.

188 other platelets onto aggregates via ADP and TxA2 release.

189 VPC31143 increased thromboxane A2 (TXA2) release from TA of wild-type, TP-KO, and LPA2-KO m

190 ced Erk2 phosphorylation and thromboxane A2 (TXA2) release were completely blocked by PP2, an Src fam

191 by a SOD mimetic or antagonists of COX-1 or TxA2-S but normalized by antagonists of COX-2 or TP-R.

192 clooxygenase (COX), thromboxane A2 synthase (TxA2-S), thromboxane prostanoid receptors (TP-Rs), or su

193 ADP, thrombin, or thromboxane A2 (TxA2) signaling through their respective Gq-coupled rece

194 r-cGMP) potently inhibited activation of the TXA2-specific GTPase in platelet membranes in a concentr

195 Large scale expression of TXA2 synthase (TXAS) is very useful for studies of the r

196 Similarly, the TXA2 synthase inhibitor/receptor antagonist ridogrel abo

197 mbination of a 5-HT2 receptor antagonist and TXA2 synthase inhibitor/receptor may be useful for atten

198 the cGMP signaling pathway independently of TXA2 synthesis and also indicate that Lyn is critically

199 e in selectively mediating GPIb-IX-dependent TXA2 synthesis and thrombosis and represents a potential

200 inhibitor] or furegrelate [a thromboxane A2 (TXA2) synthesis inhibitor] 5 min prior to the injection

201 ar but is thought to involve thromboxane A2 (TXA2) synthesis.

202 boxane synthase (TxS), and the receptors for TxA2 (the TP), PGF2alpha (the FP), and PGI2 (the IP) wer

203 The actions of TXA2 to cause vasoconstriction and platelet aggregation

204 w-found interaction between the LPA/LPA1 and TXA2/TP pathways plays significant roles in vasoregulati

205 tration of 100 nmol/L, whereas the effect of TXA2 (U46619, a stable TXA2 mimetic) on inducing prolife

206 omboxane B2 (TXB2), the stable metabolite of TXA2, via radioimmunoassay.

207 Venous production of TxA2 was higher in OZR than LZR and significantly higher

208 The biosynthesis of TXA2 was persistently increased in subjects with T1DM ve

209 tization of the receptor for thromboxane A2 (TxA2), we created a mutant TxA2 receptor (TP receptor) i

210 se both serotonin (5-HT) and thromboxane A2 (TXA2), we examined whether 5-HT and TXA2 can induce SMC

211 din endoperoxide (PGH2) into thromboxane A2 (TxA2) which plays a crucial role in hemostasis and cardi

212 of TXA2 and the interaction between 5-HT and TXA2 without affecting the response to 5-HT.