Studies on the kinetics of melatonin and N-acetylserotonin in the rat at mid-light and mid-dark.
The distribution and disappearance of melatonin and N-acetylserotonin after intravenous injection were studied at mid-light and mid-dark. Male rats were adapted under a photoperiod of 12 h light and 12 h dark cycle for a minimum of 1 week. After the intravenous injection of melatonin (10 micrograms), N-acetylserotonin (10 micrograms), or 3H-melatonin (76 ng), blood samples were collected at 1, 3, 5, 10, 20, 30, 45, 60, 75, 90, and 120 min. The concentrations of indoles in the plasma samples were determined by radioimmunoassay, while the radioactivity of 3H-melatonin was determined by scintillation counting. The distribution of melatonin and N-acetylserotonin followed a two-compartment model, showing an initial distribution phase followed by an elimination phase. The biological half-life of melatonin at mid-light and mid-dark were similar but the volume of distribution (V beta and Vc) and metabolic clearance rate (C1s) were greater at mid-dark than at mid-light. The estimated melatonin secretory rate at mid-dark was fivefold greater than that at mid-light. When 3H-melatonin was used, the half-life was significantly longer. A diurnal difference in the distribution was also evident in the N-acetylserotonin studies. The volume of distribution (V beta and Vc) was greater at mid-dark while the C1s was not significantly faster at mid-dark compared with that at mid-light. However, the estimated N-acetylserotonin secretory rate at mid-dark was eightfold greater than at mid-light.