Melatonin effect on arachidonic acid metabolism to cyclooxygenase derivatives in human platelets.
The effect of melatonin on thrombin-induced [3H]-arachidonic acid (AA) metabolism to cyclooxygenase derivatives was determined in platelets obtained from normal volunteers at 0830 and 2030 h. Percent conversion of radioactive AA was generally greater at 2030 h than at 0830 h for every cyclooxygenase derivative analyzed. Micromolar or greater concentrations of melatonin decreased significantly the conversion of [3H]-AA to prostaglandin (PG) F2 and thromboxane (Tx) B2, and inhibited slightly the conversion to PGE2 and PGD2. After preincubation of platelets with 1 mM imidazole, the melatonin inhibitory effect was significant for PGF2 only. Melatonin (10(-6) M) showed a significant inhibitory influence on platelet ATP release induced by phorbol-12 myristate-13 acetate (PMA) at 2030 h, an effect inhibited by 1 mM aspirin. These results indicate that at pharmacological concentrations melatonin inhibits human platelet cyclooxygenase.
Martinuzzo
M
M
Departamento de Fisiología, Facultad de Medicina, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Argentina.
Del Zar
M M
MM
Cardinali
D P
DP
Carreras
L O
LO
Vacas
M I
MI
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002940:Circadian Rhythm / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016718:Arachidonic Acid; D000255:Adenosine Triphosphate; D011451:Prostaglandin-Endoperoxide Synthases; D008550:Melatonin; D013755:Tetradecanoylphorbol Acetate