Em. Vanderaa et al., UPTAKE OF CIMETIDINE INTO SYNCYTIAL MICROVILLUS MEMBRANE-VESICLES OF HUMAN TERM PLACENTA, The Journal of pharmacology and experimental therapeutics, 276(1), 1996, pp. 219-222
Uptake of the H-2-receptor antagonist, cimetidine, into syncytial micr
ovillus membrane vesicles of human term placenta was investigated to c
larify whether an active transport mechanism can be responsible for th
e observed barrier of the human placenta for cimetidine, Imposition of
an outwardly directed H+-gradient stimulated cimetidine uptake, resul
ting in a small transient overshoot, The H+-gradient-dependent peak up
take was decreased under voltage-clamped conditions by carbonyl cyanid
e p-trifluoromethoxy-phenylhydrazone, suggesting the presence of an or
ganic cation-proton exchange mechanism. Uptake was partially, but sign
ificantly, inhibited by organic cation transport inhibitors, H-2-recep
tor antagonists and several other cationic drugs, providing further ev
idence for mediated uptake. H+-gradient-dependent cimetidine uptake wa
s saturable and characterized by a low-affinity (K-m) of 6.3 mM and V-
max of 17.5 nmol/mg protein/10 sec. We conclude that the system cannot
play an important role in the barrier function of the human placenta
in the transport of cimetidine. Rather than active transport, other fa
ctors, as for instance the degree of ionization of cimetidine at physi
ological pH, seem to be a more likely explanation for the low clearanc
e of cimetidine across the human placenta.