Elevation of the cyclic GMP concentration in human platelets by sodium ascorbate and 5-hydroxytryptamine.
Sodium L-ascorbate (ascorbate) and sodium D-ascorbate produced a dose-related rise of guanosine 3':5'-cyclic monophosphate (cGMP) in platelets with a maximum increment averaging 25-fold at 5 mM ascorbate. The ascorbate-induced increment in cGMP reached a peak after 1 min and was maintained for 1 h in the presence of ascorbate. 5-hydroxytryptamine (5-HT) also produced a dose-related rise of cGMP in platelets with a peak effect of approximately 25-fold at 16 micrometer 5-HT. The elevation of cGMP in platelets by both ascorbate and 5-HT did not require extracellular calcium and was blocked by inhibitors of cyclo-oxygenase such as aspirin or indomethacin. A maximum ascorbate-induced rise in platelet cGMP at the time of addition of epinephrine, collage or thrombin did not augment the release of [14C]5-hydroxytryptamine ([14C]5-HT) measured over 30 min. Although ascorbate appeared to increase platelet cGMP by modulation of endoperoxide formation, its failure to aggregate platelets or to influence the release reaction indicates that the ascorbate-stimulated rise in cGMP does not have a simple relationship to thromboxane formation.
D001205:Ascorbic Acid / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D006152:Cyclic GMP / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D012701:Serotonin / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
D012701:Serotonin; D003094:Collagen; D013917:Thrombin; D006152:Cyclic GMP; D001205:Ascorbic Acid; D001241:Aspirin; D004837:Epinephrine