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

The binding of H-3-melatonin to human serum proteins was investigated by equilibrium dialysis at 37 degrees C and pH 7.4. The binding to serum was moderate (53%) for physiological melatonin concentrations below 1 nmol/l. alpha(1)-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, gamma-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 alpha(1)-acid glycoprotein and the nonsaturable component resulted from the low-affinity binding to albumin. The number of binding sites was 0.36/molecule of alpha(1)-acid glycoprotein, when either pure alpha(1)-acid glycoprotein or serum were studied, indicating that only a fraction of alpha(1)-acid glycoprotein bound melatonin. The observed binding parameters did not enable simulation of the observed serum binding, and melatonin binding to an alpha(1)-acid glycoprotein-albumin mixture was higher than that expected from the binding to each isolated protein. The high-affinity melatonin binding to alpha(1)-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 al-acid glycoprotein concentration.