Nitric oxide donors induce extrusion of cyclic GMP from isolated human blood platelets by a mechanism which may be modulated by prostaglandins

International Journal of Cardiology
W RadziszewskiG Chaudhuri

Abstract

In the presence of 3-isobutyl-methylxanthine (IBMX), induction of cyclic 3',5'-guanosine monophosphate (GMP) production in human washed platelets (HWP) by nitric oxide donors (NOD) is followed by its accumulation in the surrounding medium in a time- and concentration-dependent manner. Thirty minutes incubation of HWP with 3-morpholino-sydonimine (SIN-1, 10 microM) at 37 degrees C resulted in a 4.6-fold increase of cyclic GMP in platelets, whereas in the extracellular medium the increase was 17.6-fold. Similar results were obtained when other NOD such as S-nitroso-N-acetylpenicyllamine (SNAP) and 3-(2-methoxy-5-chlorophenyl)oxatriazol-5-imine (GEA 3184) and the selective phosphodiesterase inhibitor, zaprinast (M&B 22948, 10 microM), were used. Probenecid (1-300 microM), an inhibitor of organic anion transport, or ouabain (1-300 microM), an inhibitor of Na+/K+ adenine triphosphate (ATP)-ase had no effect on cyclic GMP production or extrusion after stimulation with SIN-1. Significantly prostaglandin A1 (PGA1) and prostaglandin D2 (PGD2) inhibited the efflux of cyclic GMP from platelets induced by SNAP (10 microM) in a concentration-dependent fashion, with an IC50 of 63 +/- 16 and 143 +/- 17 microM, respectively. These studies sugg...Continue Reading

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Citations

Aug 18, 2004·Neurochemistry International·Georg Sager
Feb 10, 2009·Free Radical Biology & Medicine·Paul R S BakerBruce A Freeman
Jan 8, 2015·Journal of Evidence-based Complementary & Alternative Medicine·Siavash BabajafariArman Zargaran
Jun 20, 1998·Arteriosclerosis, Thrombosis, and Vascular Biology·Y NakanoM Kambe
Sep 10, 2015·Biomedit︠s︡inskai︠a︡ khimii︠a︡·N Y Rusetskaya, V B Borodulin

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