alpha-Methyldopa and the erythrocyte membrane.

Alpha-methyldopa binds to human erythrocyte membrane proteins. A portion of this binding is readily dissociable in SDS but a significant amount is very tightly bound and does not come off even under rigorous conditions. The binding is increased under oxidizing conditions and very much inhibited in the presence of reducing agents as well as superoxide dismutase and catalase. Haemoglobin competes with membrane peptides for alpha-methyldopa binding. It is postulated that haemoglobin acts as a 'sink' for the drug in the intact cell and that the first step in the pathogenesis of Coombs positivity and haemolytic anaemia results from an alteration of a critical membrane peptide secondary to binding of the drug during normal membrane breakdown.