Inhibitory effect of alcohol on cyclic GMP accumulation in human platelets

• Published in: Thrombosis research Vol. 80; no. 2; pp. 143 - 151
• Main Authors: Dong, Quan Sheng, Wroblewska, Barbara, Myers, Adam K.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 15.10.1995; Elsevier Science
• Subjects: alcohol; Biological and medical sciences; Blood coagulation. Blood cells; Blood Platelets - drug effects; Blood Platelets - metabolism; cyclic GMP; Cyclic GMP - antagonists & inhibitors; Cyclic GMP - blood; ethanol; Ethanol - pharmacology; Fundamental and applied biological sciences. Psychology; Guanylate Cyclase - drug effects; Guanylate Cyclase - metabolism; Humans; M&B22948; Molecular and cellular biology; Nitroprusside - pharmacology; Phosphodiesterase Inhibitors - pharmacology; Platelet; Platelet Activation - drug effects; Platelet Activation - physiology; platelets; Purinones - pharmacology; Radioimmunoassay; Signal Transduction - physiology; zaprinast; alcohol; zaprinast; M&B22948; ethanol; platelets; cyclic GMP; Human; Venous blood; Ethanol; Enzyme; Phosphorus-oxygen lyases; Alcohol; 3',5'-GMP; Lyases; Guanylate cyclase; In vitro; Biological activity; Platelet; Mechanism of action
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/0049-3848(95)00160-S

The effects of ethanol on cyclic GMP (cGMP) in washed human platelets were studied in the presence and absence of sodium nitroprusside (SNP), a nitric oxide donor which stimulates guanylate cyclase. SNP stimulated cGMP accumulation in a dose-dependent fashion. After 1 min exposure to 100 μM SNP, the level of cGMP was approximately four-fold that in vehicle-treated platelets. Alcohol had no effect on basal cGMP, but inhibited SNP-induced cGMP accumulation at 17, 85 and 170 mM. In further experiments, platelets were incubated for 0, 0.5, 1, 2 or 5 min with 10 μM SNP, with or without 100 μM zaprinast, a selective cGMP-phosphodiesterase (PDE) inhibitor and 85 mM ethanol. In the presence of zaprinast but not alcohol, cGMP levels rose continuously, to 10-fold the basal level at 5 min. Without zaprinast, cGMP levels were lower and reached a plateau by 2 min. Accumulation of cGMP was attenuated by alcohol 2 and 5 min after SNP addition, both in zaprinast-treated platelets and those without zaprinast. Thus, alcohol inhibits platelet cGMP accumulation stimulated by a nitric oxide donor. Its mechanism probably does not involve a major effect on PDE, because the inhibition was observed in the presence or absence of zaprinast. We hypothesize that alcohol inhibits guanylate cyclase, contributing to its complex functional effects in platelets.