Melatonin high-affinity binding to alpha-1-acid glycoprotein in human serum.

The binding of 3H-melatonin to human serum proteins was investigated by equilibrium dialysis at 37 °C and pH 7.4. The binding to serum was moderate (53%) for physiological melatonin concentrations below 1 nmol/l. α1-Acid glycoprotein and albumin bound melatonin with high 27 ± 3 and low 1.5 ± 0.1 (mmol/l)–1 affinity, respectively. Melatonin binding to other serum proteins, γ-globulins and lipoproteins was not significant. The serum binding was characterized by a saturable and a nonsaturable component. The saturable component resulted from the high-affinity binding to α1-acid glycoprotein and the nonsaturable component resulted from the low-affinity binding to albumin. The number of binding sites was 0.36/molecule of α1-acid glycoprotein, when either pure α1-acid glycoprotein or serum were studied, indicating that only a fraction of α1-acid glycoprotein bound melatonin. The observed binding parameters did not enable simulation of the observed serum binding, and melatonin binding to an α1-acid glycoprotein-albumin mixture was higher than that expected from the binding to each isolated protein. The high-affinity melatonin binding to αi-acid glycoprotein might result from a potentiation of the binding interaction by albumin and the amount of melatonin bound in plasma might vary according to the α1-acid glycoprotein concentration.