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Amino Acids

, Volume 47, Issue 9, pp 1779–1793 | Cite as

A review and discussion of platelet nitric oxide and nitric oxide synthase: do blood platelets produce nitric oxide from l-arginine or nitrite?

  • Stepan GambaryanEmail author
  • Dimitrios TsikasEmail author
Review Article
Part of the following topical collections:
  1. Homoarginine, Arginine and Relatives

Abstract

The NO/sGC/cGMP/PKG system is one of the most powerful mechanisms responsible for platelet inhibition. In numerous publications, expression of functional NO synthase (NOS) in human and mouse platelets has been reported. Constitutive and inducible NOS isoforms convert l-arginine to NO and l-citrulline. The importance of this pathway in platelets and in endothelial cells for the regulation of platelet function is discussed since decades. However, there are serious doubts in the literature concerning both expression and functionality of NOS in platelets. In this review, we aim to present and critically evaluate recent data concerning NOS expression and function in platelets, and to especially emphasise potential pitfalls of detection of NOS proteins and measurement of NOS activity. Prevailing analytical problems are probably the main sources of contradictory data on occurrence, activity and function of NOS in platelets. In this review we also address issues of how these problems can be resolved. NO donors including organic nitrites (RONO) and organic nitrate (RONO2) are inhibitors of platelet activation. Endogenous inorganic nitrite (NO2 ), the product of NO autoxidation, and exogenous inorganic nitrite are increasingly investigated as NO donors in the circulation. The role of platelets in the generation of NO from nitrite is also discussed.

Keywords

sGC cGMP Nitric oxide Mass spectrometry Nitric oxide synthase Pitfalls Platelets 

Abbreviations

CA

Carbonic anhydrase

DAF

Diaminofluorescein

DAN

Diaminonaphthalene

ECNICI

Electron-capture negative-ion chemical ionization

EI

Electron ionization

GC

Gas chromatography

sGC

Soluble guanylyl cyclase

cGMP

Cyclic guanosine monophosphate

IP

Immunoprecipitation

LOD

(Lower) limit of detection

LOQ

(Lower) limit of quantitation

MS

Mass spectrometry

NAT

Naphthotriazol

NO

Nitric oxide

NOS

Nitric oxide synthase

eNOS

Endothelial NOS

iNOS

Inducible NOS

nNOS

Neuronal NOS

PDE

Phosphodiesterase

PFB

Pentafluorobenzyl

PFB-Br

Pentafluorobenzyl bromide

PKG

cGMP-dependent protein kinase

RSD

Relative standard deviation

SIM

Selected-ion monitoring

VASP

Vasodilator stimulated phosphoprotein

WF/R

von Wildebrandt factor/ristocetin

Notes

Acknowledgments

Financial support was granted to SG (Russian Fund of Fundamental Research 15-04-02438) and to DT (TS 60/4-1) from the Deutsche Forschungsgemeinschaft (Germany). We thank the reviewers for their useful comments and suggestions which helped improve our manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The studies reported in this article were approved by the Ethics Committee of the Hannover Medical School.

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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  1. 1.Sechenov Institute of Evolutionary Physiology and BiochemistryRussian Academy of SciencesSt. PetersburgRussia
  2. 2.Centre of Pharmacology and Toxicology, Bioanalytical Laboratory for Nitric Oxide, Oxidative Stress and Eicosanoids (BIOFORNOX20)Hannover Medical SchoolHannoverGermany

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