Influence of adenosine triphosphate and ABCB1 (MDR1) genotype on the P-glycoprotein-dependent transfer of saquinavir in the dually perfused human placenta
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and PathologyDepartment of Medical Sciences2008 (English)In: Human and Experimental Toxicology, ISSN 0960-3271, E-ISSN 1477-0903, Vol. 27, no 1, 65-71 p.Article in journal (Refereed) Published
BACKGROUND: The ATP-dependent drug-efflux pump, P-glycoprotein (P-gp) encoded by ABCB1 (MDR1), 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.
Place, publisher, year, edition, pages
2008. Vol. 27, no 1, 65-71 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-17395DOI: 10.1177/0960327108088971ISI: 000256144200007PubMedID: 18480151OAI: oai:DiVA.org:uu-17395DiVA: diva2:45166