S-nitrosothiols as selective antithrombotic agents - possible mechanisms.

Abstract:

:S-nitrosothiols have a number of potential clinical applications, among which their use as antithrombotic agents has been emphasized. This is largely because of their well-documented platelet inhibitory effects, which show a degree of platelet selectivity, although the mechanism of this remains undefined. Recent progress in understanding how nitric oxide (NO)-related signalling is delivered into cells from stable S-nitrosothiol compounds has revealed a variety of pathways, in particular denitrosation by enzymes located at the cell surface, and transport of intact S-nitrosocysteine via the amino acid transporter system-L (L-AT). Differences in the role of these pathways in platelets and vascular cells may in part explain the reported platelet-selective action. In addition, emerging evidence that S-nitrosothiols regulate key targets on the exofacial surfaces of cells involved in the thrombotic process (for example, protein disulphide isomerase, integrins and tissue factor) suggests novel antithrombotic actions, which may not even require transmembrane delivery of NO.

journal_name

Br J Pharmacol

authors

Gordge MP,Xiao F

doi

10.1111/j.1476-5381.2010.00670.x

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

1572-80

issue

8

eissn

0007-1188

issn

1476-5381

pii

BPH670

journal_volume

159

pub_type

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