Uptake of methylchlorpromazine by brush-border membrane vesicles from rat small intestine

The uptake of methylchlorpromazine (MCP), a quaternary derivative of chlorpromazine, was investigated using brush-border membrane vesicles isolated from rat small intestine. MCP was taken up rapidly by the vesicles, a major part of the uptake being due to binding to the membrane. Saturable MCP binding to the brush-border membrane was inhibited strongly by chlorpromazine, moderately by propantheline and imipramine, and slightly but significantly by methylbenactyzine and mepenzolate. However, choline and tetramethylammonium failed to exhibit any such inhibitory effect. The movement of MCP into the intravesicular space was driven by an inside-negative transmembrane electrical potential difference (TEPD) induced by NaSCN or valinomycin. There was no effect of TEPD on MCP binding to the brush-border membrane. The data suggested that both rapid binding to the brush-border membrane and inside-negative TEPD, which is present physiologically across the membrane, play a significant role in the absorptive movements of MCP across intestinal epithelium.