INHIBITION OF CHOLINE UPTAKE IN SYNCYTIAL MICROVILLUS MEMBRANE-VESICLES OF HUMAN TERM PLACENTA - SPECIFICITY AND NATURE OF INTERACTION

The potency and nature of the inhibitory effect of various cationic dr ugs on the transport of choline across the placental syncytial microvi llus membrane was investigated. Tetraethylammonium, a model substrate for organic cation transport, was a poor inhibitor. Enlarging the degr ee of alkylation of the quaternary ammonium increased the inhibitory e ffect, in proportion with increasing lipophilicity. Log concentration vs % control uptake curves showed marked differences in inhibitory pot ency for the different cationic drugs. Hemicholinium-3 inhibited media ted choline uptake in the micromolar range, whereas atropine and mepip erphenidol were less potent. The H-2-receptor antagonists cimetidine, ranitidine, and famotidine inhibited choline uptake in the millimolar ranges. Dixon analysis revealed a competitive nature of inhibition for hemicholinium-3 and atropine (K-i = 40 mu M and 1.2 mM, respectively) . Cimetidine interacted noncompetitively (K-i = 3.4 mM). Since relativ ely high concentrations were needed to reach half maximal inhibition, impairment of fetal choline supply due to maternal drug use during pre gnancy is not to be expected.