Developmental expression of drug metabolizing enzymes and transporter proteins in human placenta and fetal tissues.
Transporter proteins and xenobiotic metabolizing enzymes have a crucial role in the fate of xenobiotics in human body. The expression in human placenta and fetal tissues of the proteins most commonly participating in pharmaco/toxicokinetics is reviewed. In case human data are not available, relevant animal data are included. Among transporter proteins ABC transporters, monoamine transporters and organic anion transporters are pharmacologically and toxicologically of main interest. From xenobiotic enzymes, both CYP enzymes and transferases are expressed in fetal liver already during pregnancy. In the placenta, the variety of enzymes is much more restricted. During development dynamic changes occur in both xenobiotic metabolizing enzymes and drug transporters. Although the knowledge has increased substantially over the past years it is apparent from the literature that there are uncharacterized areas, especially regarding developmental expression patterns and regulation of transporters in fetal tissues and placenta. Knowledge about tissue-specific distribution and functional significance will aid our understanding of the differences in drug response and risks for adverse events during fetal development.
Myllynen
Päivi
P
University of Oulu, Institute of Biomedicine, Department of Pharmacology and Toxicology, Oulu, Finland. Paivi.myllynen@oulu.fi
Immonen
Elina
E
Kummu
Maria
M
Vähäkangas
Kirsi
K
D000818:Animals; D001692:Biological Transport; D005260:Female; D005333:Fetus / Q000201:enzymology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D015262:Xenobiotics / Q000378:metabolism / Q000493:pharmacokinetics
D026901:Membrane Transport Proteins; D015262:Xenobiotics