Modulation of 2[125I]iodomelatonin binding sites in the guinea pig spleen by melatonin injection is dependent on the dose and period but not the time.

Effects of dose, time and period of melatonin injection on 2[125I]iodomelatonin binding sites in the guinea pig spleen were studied. Guinea pigs (Dunkin-hartley), kept under 12h light/12 h darkness, were given daily intraperitoneal injections of either vehicle or 0.01, 0.1 or 1 mg melatonin/kg body weight in either early (1 hour after onset of light period) or late light period (1 hour before offset of light period) for 2 or 7 days. To study the effect of opioid antagonist on the binding, intraperitoneal injections of 2 or 20 mg naltrexone/kg body weight alone or together with 0.1 mg melatonin/kg body weight was given daily in late light period for 2 days. 2[125I]Iodomelatonin binding assays were performed on spleen membrane preparations and radioimmunoassays of melatonin levels were carried out in serum and pineal glands collected during mid-light. High dose (1 mg/kg body weight) of melatonin injection elevated the mid-light serum melatonin levels without affecting pineal melatonin levels. Early light injection group had a higher mid-light serum melatonin level. Melatonin injection for 2 days at either time points caused a dose-dependent decrease in Bmax and increase in Kd of 2[125I]iodomelatonin binding sites in the spleen. The response was independent of the time of injection. A greater suppression of binding was achieved by injecting melatonin for 7 days. Naltrexone did not affect the binding by itself and was not able to reverse the melatonin-induced suppression of binding in the spleen. The modulation of the splenic 2[125I]iodomelatonin binding sites by exogenous melatonin suggests that melatonin may act directly on the immune system to affect its function.