Active transport of quaternary ammonium compounds by the choroid plexus in vitro

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Abstract
The quaternary ammonium compounds, hexamethonium, decamethonium, and N1-methylnicotinamide (NMN) are taken up by the rabbit choroid plexus in vitro (Krebs-Ringer phosphate glucose solution, pH 7.4, 37 C, oxygen) by a process showing all the characteristics of active transport. Uptake against a concentration gradient occurs by a saturable process that is inhibited by low temperature, by anaerobic conditions, and by low concentrations of ouabain, reserpine, and certain metabolic inhibitors. Decamethonium and NMN act as competitive inhibitors of hexamethonium uptake, suggesting that the three cations share a common transport process. Hexamethonium uptake is dependent on levels of Na, K, Mg, and phosphate in the incubation medium. Hexamethonium and decamethonium, but not NMN, are bound to homogenates of choroid plexus. The characteristics of the binding are such that binding would not account for the bulk of drug accumulation seen in the intact tissue. High concentrations of p-aminohippurate do not inhibit the uptake of hexamethonium. No evidence could be obtained for active uptake of hexamethonium by subcellular particles of plexus homogenates. The transport process for quaternary ammonium compounds appears to be present in the choroid plexus of the dog, cat, and guinea pig as well as in that of the rabbit.