Transport characteristics of propantheline across rat intestinal brush border membrane

The transport mechanism of propantheline, an anti-acetylcholine quaternary ammonium compound, has been studied using brush border membrane vesicles isolated from rat small intestine. The uptake of propantheline was facilitated by the transmembrane electrical potential difference (cell interior negative) induced by NaSCN, NaI or valinomycin. But this effect was a secondary action; in the initial phase of propantheline uptake (less than 5 min), there was no facilitating effect. When the transmembrane potential difference was induced after propantheline uptake had reached a steady state, there was an overshoot of the drug. Therefore, it is suggested that the transport of propantheline across the brush border membrane consists of at least two processes. In the first, propantheline rapidly binds to the brush border membrane, in the second it enters into epithelium driven by the negative transmembrane electrical potential difference. Cationic tertiary amines such as chlorpromazine, imipramine and promethazine markedly inhibited propantheline uptake. These results suggest that there is a common absorption process for tertiary amines and quaternary ammonium compounds.