Placental membranes

Although a uniform nomenclature for Na /H exchanger isoforms has not yet been adopted, we will refer to the amiloride-sensitive type of Na" /H exchanger that is present in the basolateral membrane of epithelia (apical membrane of placental syncytiotrophoblast) and also widely distributed in non-epithelial cells as the sensitive-type. The relatively amiloride-resistant isoform present in apical mem-... 

Fatty liver of pregnancy Placental abruption Preeclampsia/eclampsia Retained fetus syndrome Pulmonary syndrome syndrome Empyema Hyaline membrane disease... 

Within the OAT family, OAT4 is the only transporter expressed at appreciable levels in both the placenta and in the kidney [54]. The membrane localization of OAT4 within these tissues has not been examined. Steroid sulfates, and ochratoxinA are efficient transport substrates of OAT4, whereas PAH is weakly transported [54]. The functional importance of OAT4 in regulating placental permeability and renal drug elimination is currently unknown. 

Breast Cancer Resistance Protein (BCRP, also known as MXR or ABCP), first cloned from mitoxantrone and anthracycline-resistant breast and colon cancer cells [188, 189] is a half-transporter efflux pump believed to function as a homo-or hetero-dimer. Following its identification, BCRP-mediated drug resistance was observed for topoisomerase inhibitors including camptothecins [190, 191] and in-dolocarbazoles [192]. In normal tissues, BCRP was detected in placental syncytio-trophoblasts, hepatocyte canalicular membrane, apical intestinal epithelia and vascular endothelial cells [193]. These findings support the important role BCRP plays in modulating topotecan bioavailability, fetal exposure and hepatic elimination [194]. Considering that the substrates and tissue distributions for BCRP overlap somewhat with MDR1 and MRPs [195], additional studies will be required to define the relative contribution of each of these transporters in the overall and tis-... 

Mirex has considerable potential for chronic toxicity because it is only partly metabolized, is eliminated very slowly, and is accumulated in the fat, liver, and brain. The most common effects observed in small laboratory mammals fed mirex included weight loss, enlarged livers, altered liver enzyme metabolism, and reproductive failure. Mirex reportedly crossed placental membranes and accumulated in fetal tissues. Among the progeny of mirex-treated mammals, developmental abnormalities included cataracts, heart defects, scoliosis, and cleft palates (NAS 1978 Blus 1995). 

IgG comprises some 80% of the total immunoglobulin in plasma and because it is relatively small it is capable of crossing membranes and diffusing into the extravascular body spaces. It can cross the placental membrane and provides the major immune defence during the first few weeks of life until the infant s own immune mechanism becomes effective. 

It should be mentioned that the placental villous fragments can be used to measure uptake into the syncytiotrophoblast layer but they cannot be used for trans-cellular transport studies. If the transporter is expressed in the microvillous border membrane, the effects of various factors on transporter function can be determined. Another disadvantage is that the villous fragments may be heterogenous in composition and hence, uptake experiments may not be reflective of syncytiotrophoblast uptake alone. 

It needs to be mentioned here that there remains some controversy over the placental expression of P-gp as a function of gestational age. An immunohis-tochemical study done by Macfarland et al. showed that P-gp was localized to the microvillous border of trophoblasts in first trimester placenta, but not in term placenta [85], Subsequent studies refuted this to show that MDR1 mRNA is present throughout pregnancy [94], More recently, enzyme-linked immunosorbent assay (ELISA) performed in syncytial microvillous membrane showed that P-gp protein expression in early gestational age placenta is about... 

F. Ushigome, N. Koyabu, S. Satoh, K. Tsukimori, H. Nakano, T. Nakamura, T. Uchiumi, M. Kuwano, H. Ohtani, and Y. Sawada. Kinetic analysis of P-glycoprotein-mediated transport by using normal human placental brush-border membrane vesicles. Pharm Res. 20 38-44 (2003). 

J.D. Glazier and C.P. Sibley. In vitro methods for studying human placental amino acid transport Placental plasma membrane vesicles. Methods Mol Med. 122 241-252 (2006). 

Annexin V is a human placental anticoagulant protein of molecular weight 35kDa that binds to membranes and lipid bilayers containing phosphatidylserine in the presence of free calcium. Annexin V binding to cell surfaces said to result from transmembrane movement of... 

Nicotine is well absorbed from the mucous membranes in the oral cavity, gastrointestinal tract, and respiratory system. If tobacco smoke is held in the mouth for 2 seconds, 66 to 77% of the nicotine in the smoke will be absorbed across the oral mucosa. If tobacco smoke is inhaled, approximately 90 to 98% of the nicotine will be absorbed. Nicotine is distributed throughout the body, readily crossing the blood-brain and placental barriers. The liver, kidney, and lung metabolize approximately 80 to 90% of the alkaloid. The kidney rapidly eliminates nicotine and its metabolites. 

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