Effect of cholephilic organic anions on atp-dependent bile acid transport across the apical membrane of human term trophoblast
Keywords:
Transport, Placenta, Bile Acids., Adenosine triphosphate.Abstract
Bile acid (BA) transfer from the fetus to the mother across the placenta involves
trophoblastic uptake and extrusion through the apical membrane to reach the maternal
blood. The later process involves two components one dependent on the ATP hydrolysis
(ATPdep) and another one independent on this energy (ATPindep). Using apical plasma
membrane vesicles obtained from human term placenta, the sensitivity ofboth components
of glycocholate (GC) uptake to the presence of several cholephilic organic anions
(COAs) was investigated. No effect was found on ATPindep GC transport in the
presence of the BAs ursodeoxycholate and deoxycholate, while they induced a marked
stimulation of the ATPdep GC uptake. Moreover, in the presence of COAs such as
fusidic acid, rifampicin and indocyanin green, A TPdep GC uptake was al so strongly
increased. Stimulation of ATPdep GC transport induced by sorne BAs and COAs, did
not directly depend upon enhancement in the rate of A TP hydrolysis. Therefore an
interaction with the translocating function of the carrier rather that with its energetic is
suggested. The existence of sensibility of A TPdep GC transport to staurosporin, an
inhibitor of the protein kinase C, suggests that the stimulation produced by sorne COAs
on GC uptake involves somehow the action of protein kinase C, and hence the existence
of different degree of phosphorilation and activity of the carrier protein.
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