Transport of cimetidine by the rat choroid plexus in vitro.

To characterize the transport system of cimetidine, an organic cation, in the blood-cerebrospinal fluid barrier, the accumulation of cimetidine by the isolated rat choroid plexus was examined. Accumulation of cimetidine was against a concentration gradient via a saturable process (Km = 53 microM, Vmax = 12 nmol/ml/min) that was inhibited by sulfhydryl reagents (p-hydroxymercuribenzoate), metabolic inhibitors (KCN and 2,4-dinitrophenol) and hypothermia (Q10 = 4.5), but did not require inward Na+ gradient. Organic cations such as 1N-methylnicotinamide, tetraethylammonium, choline, histamine and creatinine did not affect the accumulation of cimetidine at the concentration of 1 mM. Cimetidine did not affect the accumulation of tetraethylammonium. More lipophilic cations such as quinidine and quinine inhibited not only the accumulation of cimetidine but also that of an organic anion, benzylpenicillin, although the inhibitory mechanisms are not known. One millimolar of organic anions, such as 5-hydroxyindoleacetic acid, p-aminohippuric acid, homovanillic acid, salicylic acid and benzylpenicillin, inhibited the accumulation of cimetidine. Furthermore, the accumulation of organic anions (benzylpenicillin and salicylic acid) showed saturability and was inhibited by cimetidine. Cimetidine and the organic anions thus showed a mutual inhibition. Oligopeptides also inhibited the accumulation of cimetidine. These findings suggested that cimetidine transport in the choroid plexus is via carrier-mediated active transport process, but does not require inward Na+ gradient. This transport is inhibited by several compounds with different properties like oligopeptides, lipophilic cations and organic anions, although the inhibitory mechanism is not known.