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.