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Influence of adenos...
Influence of adenosine triphosphate and ABCB1 (MDR1) genotype on the P-glycoprotein-dependent transfer of saquinavir in the dually perfused human placenta
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Rahi, M. (author)
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Heikkinen, T. (author)
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Hakkola, J. (author)
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Hakala, K. (author)
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- Wallerman, Ola (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- Wadelius, Mia (author)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos
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- Wadelius, Claes (author)
- Uppsala universitet,Institutionen för genetik och patologi
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Laine, K. (author)
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(creator_code:org_t)
- 2008-01-01
- 2008
- English.
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In: Human and Experimental Toxicology. - : SAGE Publications. - 0960-3271 .- 1477-0903. ; 27:1, s. 65-71
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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