Placenta characteristics

Wu, X., et al. Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim. Biophys. Acta 2000, 1466, 315-327. 

Estradiol is the most important of the estrogens. Like progesterone, it is synthesized by the ovaries and, during pregnancy, by the placenta as well. Estradiol controls the menstrual cycle, it promotes proliferation of the uterine mucosa, and is also responsible for the development of the female secondary sexual characteristics (breast, fat distribution, etc.). 

Ethanol readily passes across the placenta and into the fetal circulation. The fetal alcohol syndrome has three primary features microcephaly, prenatal growth deficiency, and short palpebral fissures Other characteristics include postnatal growth deficiency, fine motor dysfunction, cardiac defects, and anomalies of the external genitalia and inner ear. A definite risk of producing fetal abnormalities occurs when ethanol consumption by the mother exceeds 3 oz daily, the equivalent of about six drinks. 

In terms of ADMET, following oral administration about half of the atenolol dose is absorbed. Plasma-protein binding is minimal (3-5%). Peak plasma concentrations, as well as peak action, are reached in 2-4 h. Atenolol has low lipid solubility, and only small amounts cross the blood-brain barrier. Thus, atenolol s CNS side effects are less than with other beta-blockers [75]. Atenolol is excreted mainly by the kidneys, with little or no hepatic metabolism. It crosses the placenta, and concentrations in breast milk can be similar or even higher than those in maternal blood [76]. Atenolol is not recommended in asthma, even though its high beta-1 selectivity makes it safer in obstructive pulmonary disease than nonselective beta-blocking agents. Atenolol s important ADMET characteristics are listed in Tab. 8.2. 

In animals, THC crosses the placenta and is excreted in breast milk. There is conflicting evidence concerning teratogenicity in animals, but no definitive evidence in man. However, there have been many anecdotal reports of abnormalities. Although these were without consistent characteristics, the descriptions would readily fit the fetal alcohol syndrome (133-136) and clinical evaluation of the use of cannabis during pregnancy is complicated by the frequent concomitant use of alcohol and tobacco. 

Enalapril, captopril, and lisinopril (and presumably other ACE inhibitors) cross the placenta in pharmacologically significant amounts (17). There is clear evidence of fetotoxicity when ACE inhibitors are used beyond the first trimester of pregnancy. Since continuation of treatment beyond the first trimester carries an excess risk of low fetal birth weight and other more severe complications, it is important to withdraw the ACE inhibitor at this time. Intrauterine growth retardation, oligohydramnios, and neonatal renal impairment, often with a serious outcome, are characteristic (98) failure of ossification of the skuU or hypocalvaria also appear to be part of the pattern (17). There is also evidence that persistence of a patent ductus arteriosus is also more likely to occur. 

The resolution of the isozymes of human alkaline phosphatase in normal individuals by starch-gel electrophoresis was systematically studied in 1961 by Boyer, who observed a characteristic alkaline phosphatase pattern similar in pregnancy sera and in placenta (B38). With regard to placenta, recent work (H5, R15, R16) has indicated genetic variation of placental alkaline phosphatase in human placenta when the starch-gel electrophoresis is carried out at two different pH s (8.6 and 6.0). Other tissues could not be differentiated by their starch-gel patterns by Boyer (B38, B39). 

Stevenson (S47) and Port and Van Venrooy (P14) were able to demonstrate alkaline phosphatase activity following agar-gel electrophoresis. This technique was further developed by Haije and DeJong (HI), who obtained characteristic separate bands for liver and bone alkaline phosphatases. Dymling (D24) applied the technique to pregnancy serum and placenta. 

The alkaline phosphatase of both human intestine and placenta are L-phenyl-alanine-sensitive and undergo uncompetitive inhibition to the same extent (nearly 80%) by 0.005 M L-phenylalanine. However, we have been able to find several distinguishing biochemical characteristics of the two enzymes (1) the anodic mobility of intestinal alkaline phosphatase remains unchanged after neuraminidase treatment, whereas the placental enzyme is sialidase-seusitive and hence the electrophoretic mobility on starch gel is considerably reduced by such treatment, (2) the Michaelis constant of placental alkaline phosphatase at a definite pH is appreciably higher than that of the intestinal enzyme (at pH 9.3 the Km values of placenta and intestine are 316 and 160 ixM, respectively), and (3) the pH optima (with 0.018 Af phenyl phosphate as substrate) of the two enzymes are different the values for intestinal and placental enzymes with 0.006 Af n-phenylalanine are 9.9 and 10.6, respectively, and the respective values in the presence of 0.005 Af L-phenylalanine are 10.2 and 11.1. Finally, contrary to the behavior of intestinal alkaline phosphatase, placental enzyme is completely heat stable (P19). 

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