Diaphorase Can Metabolize Some Vasorelaxants to NO and Eliminate NO Scavenging Effect of 2-Phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO)

Title:

Diaphorase Can Metabolize Some Vasorelaxants to NO and Eliminate NO Scavenging Effect of 2-Phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO)

Creator:

Bartík, P., Chalupský, K., Vavruška, L., Muller, B., Entlicher, G., and Stoclet, J.-C.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:aac7cd27-675b-4781-a7db-fd31a59f6355
uuid:aac7cd27-675b-4781-a7db-fd31a59f6355

Subject:

Formaldoxime metabolism, Glycerol trinitrate metabolism, Diaphorase, and 2-Phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) reduction

Type:

article, model:article, and TEXT

Description:

Diaphorase was studied as a possible oxidoreductase participating in NO production from some vasorelaxants. In the presence of NADH or NADPH, diaphorase can convert selected NO donors, glycerol trinitrate (GTN) and formaldoxime (FAL) to nitrites and nitrates with NO as an intermediate. This activity of diaphorase was inhibited by diphenyleneiodonium (DPI) (inhibitor of some NADPH-dependent flavoprotein oxidoreductases), while it remained uninhibited by NG-nitro-L-arginine methyl ester (inhibitor of NO synthase) 7-Ethoxyresorufin (inhibitor of cytochrome P-450 1A1 and cytochrome P-450 NADPH-dependent reductase) inhibited the conversion of GTN only. Existence of NO as an intermediate of the reaction was supported by results of electron paramagnetic resonance spectroscopy. In addition to its ability to affect the above mentioned NO donors, diaphorase was able to reduce 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) and thus to eliminate its NO scavenging effect. This activity of diaphorase could also be inhibited by DPI. The reaction of diaphorase with GTN and PTIO was not affected by superoxide dismutase (SOD) or catalase. Reaction of FAL with diaphorase was lowered with SOD by 38 % indicating the partial participation of superoxide anion probably generated by the reaction of diaphorase with NADH or NADPH. Catalase had no effect. Diaphorase could apparently be one of the enzymes participating in the metabolism of studied NO donors to NO. The easy reduction and consequent elimination of PTIO by diaphorase could affect its use as an NO scavenger in biological tissues

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2004 Volume:53 | Number:6

Harvested from:

CDK

Metadata only:

false