Abstract
1. The effect of S-nitroso-glutathione (GSNO), a stable nitrosothiol, on platelet activation was examined in vitro and in vivo. 2. The adhesion of human platelets to fibrillar collagen and human endothelial cell monolayers was inhibited by GSNO. 3. GSNO caused a concentration-dependent inhibition of collagen-induced platelet aggregation in vitro and decreased ADP-induced aggregation in the conscious rat. 4. Inhibition of platelet aggregation in vitro correlated with the increase in intraplatelet cyclic GMP levels. 5. The release of NO from GSNO was enhanced by platelet lysate, native glutathione and ascorbate. 6. The results show that GSNO is a carrier of NO and therefore has pharmacological activity as an inhibitor of platelet activation.
Full text
PDF![745](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d607/1907743/a582ff15b296/brjpharm00214-0115.png)
![746](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d607/1907743/70337ba98286/brjpharm00214-0116.png)
![747](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d607/1907743/f5aad98fa2d1/brjpharm00214-0117.png)
![748](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d607/1907743/7209424e8a13/brjpharm00214-0118.png)
![749](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d607/1907743/55e881bd3f90/brjpharm00214-0119.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Feelisch M., Noack E. A. Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur J Pharmacol. 1987 Jul 2;139(1):19–30. doi: 10.1016/0014-2999(87)90493-6. [DOI] [PubMed] [Google Scholar]
- Ignarro L. J., Gruetter C. A. Requirement of thiols for activation of coronary arterial guanylate cyclase by glyceryl trinitrate and sodium nitrite: possible involvement of S-nitrosothiols. Biochim Biophys Acta. 1980 Aug 13;631(2):221–231. doi: 10.1016/0304-4165(80)90297-4. [DOI] [PubMed] [Google Scholar]
- Kowaluk E. A., Fung H. L. Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols. J Pharmacol Exp Ther. 1990 Dec;255(3):1256–1264. [PubMed] [Google Scholar]
- Lieberman E. H., O'Neill S., Mendelsohn M. E. S-nitrosocysteine inhibition of human platelet secretion is correlated with increases in platelet cGMP levels. Circ Res. 1991 Jun;68(6):1722–1728. doi: 10.1161/01.res.68.6.1722. [DOI] [PubMed] [Google Scholar]
- Loscalzo J. N-Acetylcysteine potentiates inhibition of platelet aggregation by nitroglycerin. J Clin Invest. 1985 Aug;76(2):703–708. doi: 10.1172/JCI112024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maurice D. H., Haslam R. J. Molecular basis of the synergistic inhibition of platelet function by nitrovasodilators and activators of adenylate cyclase: inhibition of cyclic AMP breakdown by cyclic GMP. Mol Pharmacol. 1990 May;37(5):671–681. [PubMed] [Google Scholar]
- Meister A., Anderson M. E. Glutathione. Annu Rev Biochem. 1983;52:711–760. doi: 10.1146/annurev.bi.52.070183.003431. [DOI] [PubMed] [Google Scholar]
- Mellion B. T., Ignarro L. J., Myers C. B., Ohlstein E. H., Ballot B. A., Hyman A. L., Kadowitz P. J. Inhibition of human platelet aggregation by S-nitrosothiols. Heme-dependent activation of soluble guanylate cyclase and stimulation of cyclic GMP accumulation. Mol Pharmacol. 1983 May;23(3):653–664. [PubMed] [Google Scholar]
- Mendelsohn M. E., O'Neill S., George D., Loscalzo J. Inhibition of fibrinogen binding to human platelets by S-nitroso-N-acetylcysteine. J Biol Chem. 1990 Nov 5;265(31):19028–19034. [PubMed] [Google Scholar]
- Myers P. R., Minor R. L., Jr, Guerra R., Jr, Bates J. N., Harrison D. G. Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. Nature. 1990 May 10;345(6271):161–163. doi: 10.1038/345161a0. [DOI] [PubMed] [Google Scholar]
- Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
- Park J. W. Reaction of S-nitrosoglutathione with sulfhydryl groups in protein. Biochem Biophys Res Commun. 1988 Apr 29;152(2):916–920. doi: 10.1016/s0006-291x(88)80127-x. [DOI] [PubMed] [Google Scholar]
- Pierschbacher M. D., Ruoslahti E. Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature. 1984 May 3;309(5963):30–33. doi: 10.1038/309030a0. [DOI] [PubMed] [Google Scholar]
- Radomski M. W., Palmer R. M., Moncada S. An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5193–5197. doi: 10.1073/pnas.87.13.5193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Radomski M. W., Palmer R. M., Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol. 1987 Sep;92(1):181–187. doi: 10.1111/j.1476-5381.1987.tb11310.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Radomski M. W., Palmer R. M., Moncada S. The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun. 1987 Nov 13;148(3):1482–1489. doi: 10.1016/s0006-291x(87)80299-1. [DOI] [PubMed] [Google Scholar]
- Radomski M., Moncada S. An improved method for washing of human platelets with prostacyclin. Thromb Res. 1983 May 15;30(4):383–389. doi: 10.1016/0049-3848(83)90230-x. [DOI] [PubMed] [Google Scholar]
- Stamler J. S., Simon D. I., Osborne J. A., Mullins M. E., Jaraki O., Michel T., Singel D. J., Loscalzo J. S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):444–448. doi: 10.1073/pnas.89.1.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamaguchi A., Suzuki H., Tanoue K., Yamazaki H. Simple method of aequorin loading into platelets using dimethyl sulfoxide. Thromb Res. 1986 Oct 15;44(2):165–174. doi: 10.1016/0049-3848(86)90132-5. [DOI] [PubMed] [Google Scholar]