Inhibition of human platelet aggregation and thromboxane B2 production by melatonin. Correlation with plasma melatonin levels.
Plasma melatonin concentrations and the effect of melatonin on arachidonic acid (AA)-induced aggregation and thromboxane B2 (TxB2) production by platelet-rich plasma (PRP) were examined in five normal male volunteers, sampled at 2 hr intervals from 21:30 to 09:30 hr. Peak plasma melatonin concentration was found at 03:30 hr. Inhibition by 10(-6) M melatonin of AA-induced PRP aggregation was observed only in samples taken at 01:30 hr. Assessment of the inhibitory effect of 10(-9)-10(-6) M melatonin on AA-induced TxB2 production indicated that melatonin activity was greater at 01:30 h as compared to late night. Assessed as a global effect, the inhibitory activity of melatonin on PRP TxB2 showed a maximum at 01:30 hr and minimal effects at 03:30 hr, at the time when plasma concentrations of melatonin were highest. These results indicate the existence of a nocturnal variation in sensitivity of human platelets to melatonin, with a peak that precedes the maximum in circulating melatonin levels.
Vacas
M I
MI
Departamento de Fisiología, Facultad de Medicina, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Argentina.
Del Zar
M M
MM
Martinuzzo
M
M
Falcon
C
C
Carreras
L O
LO
Cardinali
D P
DP
D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D002940:Circadian Rhythm; D006801:Humans; D008297:Male; D008550:Melatonin / Q000097:blood* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011863:Radioimmunoassay; D013929:Thromboxane B2 / Q000096:biosynthesis*
D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2; D008550:Melatonin