Function of P-Glycoprotein Expressed in Placenta and Mole

Nakamura, Yukihiko; Ikeda, Shun‐ichi; Furukawa, Tatsuhiko; Sumizawa, Tomoyuki; Tani, Akira; Akiyama, Shin-ichi; Nagata, Yukihiro

doi:10.1006/bbrc.1997.6855

Cited by 107 publications

(65 citation statements)

References 21 publications

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“…The higher transfer rates of methadone in the fetal to maternal direction could be explained by the activity of the unidirectional transporter P-gp. The explanation, though speculative, was based on the localization of P-gp on the brush-border membranes of human trophoblast cells and its activity as an ATP-dependent unidirectional efflux transporter [9,32]. Indeed, the activity of P-gp in the unidirectional efflux of digoxin, vinblastine, and vincristine has been reported in Be-Wo human placental choriocarcinoma epithelial cells [11].…”

Section: Discussionmentioning

confidence: 99%

“…Of particular interest to this investigation is the identification of P-gp in placental trophoblast tissue brush-border membranes [8]. Vesicle preparations from trophoblast tissue were used to provide evidence for the function of P-gp [9]. P-gp exhibits very broad substrate structure specificity and interacts with many xenobiotics and drugs including methadone [10].…”

Section: Introductionmentioning

confidence: 99%

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Role of P-glycoprotein in transplacental transfer of methadone

Nanovskaya

Nekhayeva

Karunaratne

et al. 2005

Biochemical Pharmacology

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Methadone is the therapeutic agent of choice for treatment of the pregnant opiate addict. However, little is known on the factors affecting its concentration in the fetal circulation during pregnancy and how it might relate to neonatal outcome. Therefore, a better understanding of the function of placental metabolic enzymes and transporters should add to the knowledge of the role of the tissue in the disposition of methadone and its relation to neonatal outcome. We hypothesized that the expression and activity of the placental efflux transporter P-glycoprotein (P-gp) would affect the transfer of methadone to the fetal circulation. Data obtained utilizing dual perfusion of placental lobule and monolayers of Be-Wo cell line indicated that methadone is extruded by P-gp. Transfer of methadone to the fetal circuit was increased by 30% in the presence of the P-gp inhibitor GF120918 while the transfer of paclitaxel, a typical substrate of the glycoprotein, was increased by 50%. In the Be-Wo cell line, methadone and paclitaxel uptake was also increased in the presence of the P-gp inhibitor cyclosporin A. Moreover, the expression of P-gp in placental brush-border membranes varied between term placentas. Taken together, these data strongly suggest that the concentration of methadone in the fetal circulation is affected by the expression and activity of P-gp. It is reasonable to speculate that placental disposition of methadone affects its concentration in the fetal circulation. If true, this may also be directly related to the incidence and intensity of neonatal abstinence syndrome (NAS).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of P-glycoprotein in transplacental transfer of methadone

Nanovskaya

Nekhayeva

Karunaratne

et al. 2005

Biochemical Pharmacology

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“…Nakamura et al [13] using immunoblotting experiments also showed the expression of P-gp specifically in the human cyto-and syncytio-trophoblasts. Although P-gp in the analogous transporting trophoblast layer (labyrinth) is speculated to play a signficant role in the protection of the rodent fetus from toxic compounds [14], its function, such as transporting activity and substrate specificity in the human cyto-and syncytio-trophoblasts, remain unknown.…”

Section: Introductionmentioning

confidence: 93%

Functional expression of P-glycoprotein in primary cultures of human cytotrophoblasts and BeWo cells☆

Utoguchi

Chandorkar

Avery

et al. 2000

Reproductive Toxicology

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“…P-gp has the capacity to bind and transport different steroids [13,41,42] and is highly expressed in the apical brush-border membrane of the syncytiotrophoblast at different stages of pregnancy [43][44][45][46]. This protein could therefore play a role in the protection of the fetus both against xenobiotics [10,11] and steroids [7].…”

Section: Discussionmentioning

confidence: 99%

Glutathione-S-transferase-P1 I105V polymorphism and response to antenatal betamethasone in the prevention of respiratory distress syndrome

Oretti

Marino

Mosca³

et al. 2009

Eur J Clin Pharmacol

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PHARMACOGENETICSGlutathione-S-transferase-P1 I105V polymorphism and response to antenatal betamethasone in the prevention of respiratory distress syndrome Abstract Purpose The aim of this pilot study was to assess the association between polymorphisms in genes that encode for proteins involved in the pharmacokinetics/pharmacodynamics of glucocorticoids and the occurrence of respiratory distress syndrome (RDS) in preterm infants born to mothers treated with a complete course of betamethasone. Methods Sixty-two preterm infants were enrolled. The C1236T, G2677T, and C3435T polymorphisms in the ABCB1 gene, BclI, N363S and ER22/23EK in the NR3C1 gene, I105V in the GST-P1 gene and GST-M1 and GST-T1 deletions were analyzed, and their association with the occurrence of RDS was assessed. Results In univariate analysis, the heterozygous and homozygous presence of the I105V variant in the GST-P1 gene seemed to confer protection against the occurrence of RDS (P=0.032), while no association for all other polymorphisms was observed. In multivariate analysis, selection from the reference model of independent variables based on AIC (Akaike information criteria) maintained three variables in the model: gestation, C3435T, and GST-P1 genotype.

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Function of P-Glycoprotein Expressed in Placenta and Mole

Cited by 107 publications

References 21 publications

Role of P-glycoprotein in transplacental transfer of methadone

Role of P-glycoprotein in transplacental transfer of methadone

Functional expression of P-glycoprotein in primary cultures of human cytotrophoblasts and BeWo cells☆

Glutathione-S-transferase-P1 I105V polymorphism and response to antenatal betamethasone in the prevention of respiratory distress syndrome

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