Em. Vanderaa et al., INHIBITION OF CHOLINE UPTAKE IN SYNCYTIAL MICROVILLUS MEMBRANE-VESICLES OF HUMAN TERM PLACENTA - SPECIFICITY AND NATURE OF INTERACTION, Biochemical pharmacology, 50(11), 1995, pp. 1873-1878
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.