Chemical heterogeneity of [ 3H]imipramine binding sites on human platelet membranes

Functional groups essential for high- and low-affinity [ 3H]imipramine (IMI) binding were determined by the method of chemical modification. The high-affinity recognition sites contained cysteine and lysine amino acid residues, but not aspartic or glutamic acid residues. The low-affinity recognition sites contained only cysteine residues. Moreover, probably only part of these sites contained these residues. The arginine, tyrosine and histidine residues are not likely to be functionally important for the [ 3H]IMI binding process. Analysis of the structure-function interaction of drug molecules reveals that, for all substances with high displacement ability, there is a conformation in which they can react with high-affinity IMI recognition sites. Data obtained allowed us to construct a tentative structure model of the high-affinity recognition IMI binding site.