The placenta functions both as site for nutrition and protection of the fetus. 
Transport proteins, including members of the multidrug resistance protein 
(MRP)/ABCC subfamily, have been recognized to contribute to the latter function. 
MRP5 (ABCC5) was identified as transmembrane transport protein for cyclic 
nucleotides, especially 3',5'-cyclic GMP (cGMP), indicating an additional role 
in signal transduction and a potential role in placenta development. We 
therefore studied expression, localization, and function of MRP5 in placenta of 
different gestational ages. Quantitative real-time polymerase chain reaction 
revealed expression of MRP5 in all 60 samples from pre-term and term placenta, 
with a decreasing mean expression with gestational age (MRP5/18S-ratio x 1000; < 
32 weeks: 2.91 +/- 0.73, n = 15; 32 to 37 weeks: 2.10 +/- 0.87, n = 15; > 37 
weeks: 0.46 +/- 0.08, n = 30; P < 0.01). Immunofluorescence microscopy with an 
anti-MRP5 antibody indicated localization of MRP5 preferentially in the basal 
membrane of syncytiotrophoblasts and in and around fetal vessels. ATP-dependent 
[(3)H]cGMP transport as evidence for MRP5 function could be demonstrated in 
isolated basal membrane vesicles. Moreover, the influence of cellular 
differentiation on MRP5 expression was studied in isolated trophoblasts, 
revealing an increase of the MRP5 expression in parallel with the hCG production 
(MRP5/18S-ratio x 1000 was 2.4 +/- 0.5 at day 5 of culture and 1.45 +/- 0.5 at 
day 0 of culture, n = 3 preparations, significant difference with P < 0.05). In 
conclusion, MRP5 expression depends on gestational age and varies throughout the 
differentiation process. In view of the important role of cGMP for cellular 
differentiation, MRP5 may play a role in placental development in context with a 
specific need for cellular cGMP export.