Biomedical subjects

P Pávek

Publications and source records attributed to P Pávek.

4 recordsLinked to original sources

PubMed2002

[Physiologic function of P-glycoprotein].

P-glykoprotein has been proposed to function as a membrane transport protein for a large variety of substrates, ranging from small lipophilic molecules, steroid hormones, lipophilic peptides, some drugs, biologically important molecules and xenobiotics. There is little doubt that P-glycoprotein transports a wide range of substrates out of cells, nevertheless it is difficult to explain its wide substrate specificity and mechanism of the transport. P-glycoprotein has been found to be a major cause of acquired multidrug resistance (MDR) of cancer cells to chemotherapeutic drugs. The identification and localization of P-glycoprotein expression in a variety of normal human tissues raised the question of the physiological functions of P-glykoprotein. Currently, there is considerable evidence that P-glycoprotein can protect the body and sensitive tissues against a range of different xenobiotics. In addition, P-glycoprotein might play a role in regulation of cell differentiation, proliferation, immune response and programmed cell death.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Influence of P-glycoprotein on the transplacental passage of cyclosporine.

The transfer kinetics of cyclosporine across the dually perfused rat placenta in the maternal to fetal direction and a possible involvement of P-glycoprotein were investigated. The transplacental clearance of cyclosporine in the materno-fetal direction was found to be dependent on the maternal inflow concentration of cyclosporine. Coadministration of cyclosporine with an excess of quinidine or chlorpromazine into the maternal compartment revealed 1.7- and 1.9-fold increase in cyclosporine concentration in the fetal compartment. In the experiments where quinidine was present both in the maternal and fetal compartments, cyclosporine appeared in the fetal compartment significantly faster, and its amount was three times higher when compared with controls. Conversely, quinidine or chlorpromazine did not affect the transplacental passage of L-[(3)H]-glucose. The interference of quinidine with the metabolism of cyclosporine in the placenta was excluded because only traces of M-1 and M-17 metabolites were found in the fetal solutions. Sodium azide, a mitochondrial respiratory inhibitor, was found to double the rate of cyclosporine, but not L-[(3)H]-glucose, passage across the placenta. Our findings indicate that P-glycoprotein pumps cyclosporine out of the trophoblast cells of the rat placenta in the ATP-dependent manner and restricts the passage of cyclosporine across the placental barrier.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Unidirectional transfer of D-xylose across the rat placenta.

1. The transplacental transfer of D-xylose was investigated in the present study. 2. Umbilical perfusion of the rat term placenta was used to study materno-foetal (M-F) and foetomaternal (F-M) transfer of this compound. 3. D-Xylose was found to cross the rat term placenta very quickly in the M-F direction, with subsequent accumulation in the foetal compartment (the F-M ratio being 2.23 at the end of the experiments). In contrast, no transfer in the F-M direction was observed. 4. A possible facilitation of the transplacental transfer of D-xylose from the mother to foetus in rats is suggested.

Animals↗

PubMedDate not supplied

Corticosterone transfer and metabolism in the dually perfused rat placenta: effect of 11beta-hydroxysteroid dehydrogenase type 2.

Although rat is the most widely used model of glucocorticoid programming of the fetus, the role of rat placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in the transplacental pharmacokinetics of the naturally occurring glucocorticoid, corticosterone, has not yet been fully elucidated. In this study, expression of 11beta-HSD2 in the rat placenta on two different gestation days (16 and 22) was examined using quantitative RT-PCR and Western blotting, and dually perfused rat term placenta was employed to evaluate its functional capacity to transfer and metabolize corticosterone. Marked decrease in placental expression of 11beta-HSD2 toward term was observed on both mRNA and protein levels. In perfusion studies, increasing maternal corticosterone concentration from 3 to 200 nM resulted in the fall of 11beta-HSD2 conversion capacity from 64.3 to 16.3%, respectively. Enzyme saturation occurred at about 50 nM substrate concentration. When delivering corticosterone (3 or 100 nM) from the fetal side, a similar decline of 11beta-HSD2 conversion capacity was observed (66.5% and 48.5%, respectively). Addition of carbenoxolone (10 or 100 microM), a non-specific 11beta-HSD inhibitor, to maternal perfusate decreased conversion capacity from 66.7 to 12.6 or 8.1%, respectively. Similarly potent inhibitory effect was observed in feto-maternal studies. Neither saturation nor inhibition of 11beta-HSD2 was associated with transformation of corticosterone in metabolites other than 11-dehydrocorticosterone. These data suggest that 11beta-HSD2 is the principal enzyme controlling transplacental passage of corticosterone in rats and is able to eliminate corticosterone in both maternal and fetal circulations.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗