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Rapid S-nitrosothiol metabolism by platelets and megakaryocytes

Shah, Chirag M. and Locke, Ian C. and Chowdrey, Hardial S. and Gordge, Michael P. (2003) Rapid S-nitrosothiol metabolism by platelets and megakaryocytes. Biochemical Society Transactions, 31 (6). pp. 1450-1452. ISSN 0300-5127

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Official URL: http://www.biochemsoctrans.org/bst/031/1450/bst031...

Abstract

RSNOs (S-nitrosothiols) regulate platelet and megakaryocyte function, and may act in vivo as a nitric oxide reservoir. There is a discrepancy between the spontaneous rate of NO release from different RSNO compounds and their pharmacological effects, implying that target cells may mediate biological activity either by metabolism of RSNOs or by displaying cell surface receptors. In the present study, we sought evidence for rapid cell-mediated metabolism of RSNOs. Exposure of platelets to GSNO (S-nitrosoglutathione) for as little as 5 s inhibited thrombin-induced platelet aggregation by >95%; however, AlbSNO (S-nitrosoalbumin) was much less effective over these short time periods. Incubation of 1 mM GSNO or AlbSNO with platelets and megakaryocytes resulted in a 25-34% loss of RSNO recoverable from the supernatant (P<0.02) within 30 s. This rapid cell-mediated RSNO decay did not progress further over 5 min, and could not be accounted for by release of free NO. The g-glutamyl transpeptidase inhibitor acivicin (100 mM) partially decreased GSNO decay, whereas the membrane-impermeable thiol-blocking agent 5.5'-dithiobis-(2-nitrobenzoic acid) (100 mM) completely blocked cell-mediated GSNO decay and partially blocked AlbSNO decay. Our results highlight differences between high- and low-molecular-mass RSNOs with regard to their rapid metabolism/uptake and subsequent cellular responses, and indicate a critical role for extracellular thiols in RSNO metabolism by platelets and megakaryocytes.

Item Type:Article
Additional Information:Online ISSN 1470-8752
Uncontrolled Keywords:cell surface thiol, gamma-glutamyl transpeptidase, megakaryocyte, nitric oxide, S-nitrosothiol, platelet.
Research Community:University of Westminster > Life Sciences, School of
ID Code:242
Deposited On:29 Nov 2005
Last Modified:11 Dec 2009 11:30

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