Beneficial Effect of Propofol on Arterial Adenosine Triphosphate-sensitive K+Channel Function Impaired by Thromboxane

Haba, Masanori; Kinoshita, Hiroyuki; Matsuda, Naoyuki; Azma, Toshiharu; Hama-Tomioka, Keiko; Hatakeyama, Noboru; Yamazaki, Mitsuaki; Hatano, Yoshio

doi:10.1097/aln.0b013e3181a918a0

Cited by 22 publications

(17 citation statements)

References 32 publications

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“…No clinically more effective XO inhibitors for the treatment of hyperuricemia have been developed other than allopurinol, an analogue of hypoxanthine which was introduced for clinical use in 1963 by Elion et al [7]. Because of shortcomings of allopurinol, new more potent inhibitors are under clinical investigation [8][9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

A comparative study of AutoDock and PMF scoring performances, and SAR of 2-substituted pyrazolotriazolopyrimidines and 4-substituted pyrazolopyrimidines as potent xanthine oxidase inhibitors

Ali

Fujita

Akaho

et al. 2009

J Comput Aided Mol Des

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4-Alkylidenehydrazino-1H-pyrazolo[3,4-d]pyrimidines, 4-arylmethylidenehydrazino-1H-pyrazolo[3,4-d]pyrimidines, and 2-substituted 7H-pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidines as potential xanthine oxidase inhibitors were docked into the active site of the bovine milk xanthine dehydrogenase using two scoring functions involved in AutoDock 3.05 and the CAChe 6.1.10. The correlation coefficiency obtained between the AutoDock binding energy and IC(50) of the inhibitors was better than that obtained by the CAChe-PMF docking score. Many ligands exhibited one to four hydrogen bonds within the active site, where the detected hydrogen bonds by CAChe was identified quantitatively in the docked conformation by using MOPAC 2002. These ligands were docked into a long, narrow channel of the enzyme leading to the molybdopterin active moiety, with hydrogen bonding and electrostatic interaction between the planar aromatic moiety of the ligand and the enzyme. Furthermore, SAR among inhibitors was investigated, which revealed that the oxo group of pyrazolopyrimidine analogs is essential for its activity and the tricyclic derivatives are shown to be more potent than bicyclic ones. The mode of interaction of the docked inhibitors was described in details.

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Section: Introductionmentioning

confidence: 99%

A comparative study of AutoDock and PMF scoring performances, and SAR of 2-substituted pyrazolotriazolopyrimidines and 4-substituted pyrazolopyrimidines as potent xanthine oxidase inhibitors

Ali

Fujita

Akaho

et al. 2009

J Comput Aided Mol Des

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“…20 Furthermore, propofol has been reported to reduce oxidative stress by inhibiting a nicotinamide adenine dinucleotide phosphate oxidase subunit. 21 The redox regulation in vitro and in vivo mainly includes the transfer of electrons and hydrogen atoms. 22 The compounds, 2,2Ј-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS, see structure and absorption spectra in fig.…”

Section: Conclusion: Propofol Scavenges Abtsmentioning

confidence: 99%

In Vitro Kinetic Evaluation of the Free Radical Scavenging Ability of Propofol

Liu

Yue

et al. 2012

Anesthesiology

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Background: Propofol is a widely used, short-acting, and intravenously administered hypnotic agent with notable antioxidant and free radical scavenging activities. However, there are relatively few kinetic studies on the free radical scavenging ability of propofol. The goal of this study is to evaluate the kinetics of propofol scavenging 2,2Ј-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical (ABTS

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“…4B). In contrast, the ATPsensitive K 1 channel blocker glibenclamide (1 mM) (Haba et al, 2009) (Cordaillat et al, 2007) had no effect on the NCA-induced vasodilation (each n 5 6) (Fig. 4, C and D, respectively).…”

Section: Resultsmentioning

confidence: 94%

Pharmacological Characterization of 1-Nitrosocyclohexyl Acetate, a Long-Acting Nitroxyl Donor That Shows Vasorelaxant and Antiaggregatory Effects

Donzelli¹,

Fischer

King

et al. 2012

J Pharmacol Exp Ther

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Nitroxyl (HNO) donors have potential benefit in the treatment of heart failure and other cardiovascular diseases. 1-Nitrosocyclohexyl acetate (NCA), a new HNO donor, in contrast to the classic HNO donors Angeli's salt and isopropylamine NONOate, predominantly releases HNO and has a longer halflife. This study investigated the vasodilatative properties of NCA in isolated aortic rings and human platelets and its mechanism of action. NCA was applied on aortic rings isolated from wild-type mice and apolipoprotein E-deficient mice and in endothelial-denuded aortae. The mechanism of action of HNO was examined by applying NCA in the absence and presence of the HNO scavenger glutathione (GSH) and inhibitors of soluble guanylyl cyclase (sGC), adenylyl cyclase (AC), calcitonin gene-related peptide receptor (CGRP), and K 1 channels. NCA induced a concentration-dependent relaxation (EC 50 , 4.4 mM). This response did not differ between all groups, indicating an endothelium-independent relaxation effect. The concentration-response was markedly decreased in the presence of excess GSH; the nitric oxide scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide had no effect. Inhibitors of sGC, CGRP, and voltagedependent K 1 channels each significantly impaired the vasodilator response to NCA. In contrast, inhibitors of AC, ATP-sensitive K 1 channels, or high-conductance Ca 21 -activated K 1 channels did not change the effects of NCA. NCA significantly reduced contractile response and platelet aggregation mediated by the thromboxane A 2 mimetic 9,11-dideoxy-11a,9a-epoxymethanoprostaglandin F 2a in a cGMPdependent manner. In summary, NCA shows vasoprotective effects and may have a promising profile as a therapeutic agent in vascular dysfunction, warranting further evaluation.

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Beneficial Effect of Propofol on Arterial Adenosine Triphosphate-sensitive K+Channel Function Impaired by Thromboxane

Abstract: Background: It is not known whether thromboxane A 2 impairs adenosine triphosphate (ATP)-sensitive K ؉ channel function via

Cited by 22 publications

References 32 publications

A comparative study of AutoDock and PMF scoring performances, and SAR of 2-substituted pyrazolotriazolopyrimidines and 4-substituted pyrazolopyrimidines as potent xanthine oxidase inhibitors

A comparative study of AutoDock and PMF scoring performances, and SAR of 2-substituted pyrazolotriazolopyrimidines and 4-substituted pyrazolopyrimidines as potent xanthine oxidase inhibitors

In Vitro Kinetic Evaluation of the Free Radical Scavenging Ability of Propofol

Pharmacological Characterization of 1-Nitrosocyclohexyl Acetate, a Long-Acting Nitroxyl Donor That Shows Vasorelaxant and Antiaggregatory Effects

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