Last update 01 Nov 2024

TBXA2R x VDCCs

Last update 01 Nov 2024

Basic Info

Related Targets

TBXA2RVDCCs

Drugs associated with TBXA2R x VDCCs

Dauricine

Target

TBXA2R x VDCCs

Mechanism

TBXA2R antagonists [+1]

Active Org.-

Originator Org.

Wuhan Medical College

Active Indication-

Inactive Indication

Arrhythmias, Cardiac [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TBXA2R x VDCCs

100 Translational Medicine associated with TBXA2R x VDCCs

0 Patents (Medical) associated with TBXA2R x VDCCs

Literatures (Medical) associated with TBXA2R x VDCCs

01 Apr 2021·European Journal of PharmacologyQ3 · MEDICINE

Effect of mitochondrial complex III inhibitors on the regulation of vascular tone in porcine coronary artery

Q3 · MEDICINE

Article

Author: Almukhtar, Hani ; Smith, Paul A ; Saarti, Mohammed ; Roberts, Richard E

In order to gain insight into the regulation of vascular tone by mitochondria, the effects of mitochondrial complex III inhibitors on contractile responses in porcine isolated coronary arteries were investigated. Segments of porcine coronary arteries were set up for isometric tension recording and concentration response curves to contractile agents were carried out in the absence or presence of the complex III inhibitors antimycin A or myxothiazol. Activity of AMP kinase was determined by measuring changes in phosphorylation of AMP kinase at Thr172. Pre-incubation with 10 μM antimycin A (Q_i site inhibitor), or myxothiazol (Q_o site inhibitor) led to inhibition of the contraction to the thromboxane receptor agonist U46619. Similar effects were seen on contractile responses to extracellular calcium, and the L-type calcium channel opener BAY K 8644, suggesting that both antimycin A and myxothiazol inhibit calcium-dependent contractions. The inhibitory effect of antimycin A was still seen in the absence of extracellular calcium, indicating an additional effect on a calcium independent pathway. The AMP kinase inhibitor dorsomorphin (10 μM) prevented the inhibitory of antimycin A but not myxothiazol. Furthermore, antimycin A increased the phosphorylation of AMP kinase, indicating an increase in activity, suggesting that antimycin A also acts through this pathway. These data indicate that inhibition of complex III attenuates contractile responses through inhibition of calcium influx. However, inhibition of the Q_i site can also inhibit the contractile response through activation of AMP kinase.

01 Dec 2020·Prostaglandins & Other Lipid MediatorsQ3 · BIOLOGY

Mechanism of thromboxane receptor-induced vasoconstriction in human saphenous vein

Q3 · BIOLOGY

Article

Author: Turkyılmaz, Gulsum ; Ozen, Gulsev ; Celik, Zeynep ; Topal, Gokce ; Norel, Xavier ; Turkyılmaz, Saygın ; Teskin, Onder ; Aljesri, Khadija

Saphenous vein (SV) is one of the most widely used graft material in patients undergoing coronary artery bypass graft surgery (CABG). Thromboxane A₂ (TXA₂) is implicated in graft failure by inducing vasoconstriction and platelet aggregation. The aim of this study is to investigate the mechanism involved in TXA₂-induced vasoconstriction in human SV. The role of different inhibitors and blockers on U46619 (TXA₂-mimetic)-induced vasoconstriction is investigated by using an isolated organ bath system. Relaxation responses to several mediators are evaluated in SV pre-contracted with U46619 and compared with those pre-contracted with phenylephrine. Our results demonstrate that U46619-induced contraction is completely blocked by myosin light chain kinase inhibitor ML-9 or TP receptor antagonist BAY u3405. Furthermore, U46619-induced contraction is partially inhibited by phospholipase C inhibitor U73122, protein kinase C inhibitor calphostin C, Rho-kinase inhibitor Y-27632, L-type calcium channel blocker nifedipine, store-operated channel inhibitor SKF96365 or removal of extracellular calcium. Relaxation responses to NO donor (sodium nitroprusside), guanylate cyclase (GC) stimulator (riociguat), phosphodiesterase (PDE) inhibitors (sildenafil, IBMX), adenylate cyclase (AC) activator (forskolin) and acetylcholine (ACh) are markedly reduced when U46619 is used as a pre-contraction agent. Our results demonstrate that influx of extracellular Ca²⁺ (through L-type calcium channels and store-operated calcium channels) and intracellular Ca²⁺ release together with Ca²⁺ sensitization (through Rho-kinase activation) are necessary components for TXA₂-induced vasoconstriction in SV. Moreover, more pronounced decrease in vasorelaxation induced by several mediators (SNP, riociguat, sildenafil, IBMX, forskolin, and ACh) in the presence of U46619 when compared with phenylephrine suggests that there is a crosstalk between the TP receptor signaling pathway and PDE, AC, GC enzymes. We believe that the investigation of mechanism of the TXA₂-induced vasoconstriction in SV will provide additional information for the prevention of SV graft failure.

01 May 2006·European Journal of PharmacologyQ3 · MEDICINE

Mechanisms underlying the vasorelaxing effects of butylidenephthalide, an active constituent of Ligusticum chuanxiong, in rat isolated aorta

Q3 · MEDICINE

Article

Author: Sunny Sun Kin Chan ; Angela On Ki Choi ; Ge Lin ; Robert Leslie Jones

Butylidenephthalide (BDPH) is one of the most potent vasorelaxants isolated from Ligusticum chuanxiong Hort. The objective of the current study is to investigate the underlying vasorelaxation mechanisms in rat aorta. In 9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F(2alpha) (U46619) precontracted preparations, endothelium removal, the nitric oxide (NO) synthase inhibitor Nomega-nitro-l-arginine methyl ester (l-NAME) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) partially inhibited the BDPH relaxation response to a similar extent. The cyclooxygenase inhibitor indomethacin, beta-adrenoceptor antagonist propranolol, adenylate cyclase inhibitors 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536) and 2',5'-dideoxyadenosine, and K(+) channel blocker tetraethylammonium had no effect. BDPH produced full relaxation against contractions induced by KCl and U46619 in the presence of the l-type voltage-operated Ca(2+) channel (Ca(v) 1.2) blocker nifedipine. In a receptor-operated Ca(2+) channel protocol where contraction was mediated by Ca(2+) re-addition in the presence of U46619 and nifedipine, BDPH produced relaxation. In the absence of extracellular Ca(2+), BDPH inhibited contractions induced by phorbol-12,13-dibutyrate and U46619. Our results suggest that BDPH-mediated vasorelaxation comprises both endothelium-dependent (NO) and independent components. It is suggested that BDPH acting through an inhibitory mechanism downstream to l-type voltage-operated and prostanoid TP receptor-operated Ca(2+) channels operating late in the contractile pathway.

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