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- Title
Influence of adenosine triphosphate and ABCB1 (MDR1) genotype on the P-glycoprotein-dependent transfer of saquinavir in the dually perfused human placenta.
- Authors
Rahi, M.; Heikkinen, T.; Hakkola, J.; Hakala, K.; Wallerman, O.; Wadelius, M.; Wadelius, C.; Laine, K.
- Abstract
Background: The ATP-dependent drug-efflux pump, P-glycoprotein (P-gp) encoded by ABCB1 (MIJR1), plays a crucial role in several tissues forming blood-tissue barriers. Absence of a normally functioning P-gp can lead to a highly increased tissue penetration of a number of clinically important drugs. Methods: We have studied the dose-response effect of exogenous ATP on the placental transfer of the well-established P-gp substrate saquinavir in 17 dually perfused human term placentas. We have also studied the influence of the ABCB1 polymorphisms 2677G>T/A and 3435C>T on placental P-gp expression (n = 44) and the transfer (n = 16) of saquinavir. Results: The present results indicate that the addition of exogenous ATP to the perfusion medium does not affect the function of P-gp as measured by saquinavir transfer across the human placenta. The variant allele 3435T was associated with significantly higher placental P-gp expression than the wild-type alleles. However, neither polymorphism affected placental transfer of saquinavir nor there was any correlation between P-gp expression and saquinavir transfer. Conclusions: Our results indicate that addition of exogenous ATP is not required for ATP-dependent transporter function in a dually perfused human placenta. Although the ABCB1 polymorphism 3435C>T altered the expression levels of P-gp in the human placenta, this did not have any consequences on P-gp-mediated placental transfer of saquinavir.
- Subjects
PLACENTA; EMBRYOLOGY; GENETIC polymorphisms; PRESERVATION of organs, tissues, etc.; GLYCOPROTEINS; P-glycoprotein; CRYOBIOLOGY; GLYCOCONJUGATES; ADENOSINE triphosphate
- Publication
Human & Experimental Toxicology, 2008, Vol 27, Issue 1, p65
- ISSN
0960-3271
- Publication type
Article
- DOI
10.1177/0960327108088971