Expression Patterns of Organic Anion Transporting Polypeptides 1B1 and 1B3 Protein in Human Pediatric Liver.
Determining appropriate pharmacotherapy in young children can be challenging due to uncertainties in the development of drug disposition pathways. With knowledge of the ontogeny of drug-metabolizing enzymes and an emerging focus on drug transporters, the developmental pattern of the uptake transporters organic anion transporting polypeptide (OATP) 1B1 and 1B3 was assessed by relative protein quantification using Western blotting in 80 human pediatric liver specimens covering an age range from 9 days to 12 years. OATP1B3 exhibited high expression at birth, which declined over the first months of life, and then increased again in the preadolescent period. In comparison with children 6-12 years of age, the relative protein expression of highly glycosylated (total) OATP1B3 was 235% (357%) in children <3 months of age, 33% (64%) in the age group from 3 months to 2 years, and 50% (59%) in children 2-6 years of age. The fraction of highly glycosylated to total OATP1B3 increased with age, indicating ontogenic processes not only at the transcriptional level but also at the post-translational level. Similar to OATP1B3, OATP1B1 showed high interindividual variability in relative protein expression but no statistically significant difference among the studied age groups.
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee (M.M.S.T., B.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.N.H.); and Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital Memphis, Tennessee (E.G.S.).
Margaret M S
MM
Thomson
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee (M.M.S.T., B.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.N.H.); and Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital Memphis, Tennessee (E.G.S.).
Ronald N
RN
Hines
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee (M.M.S.T., B.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.N.H.); and Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital Memphis, Tennessee (E.G.S.).
Erin G
EG
Schuetz
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee (M.M.S.T., B.M.); Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin (R.N.H.); and Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital Memphis, Tennessee (E.G.S.) bmeibohm@uthsc.edu.
Bernd
B
Meibohm
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006031:Glycosylation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011499:Protein Processing, Post-Translational; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3 / Q000235:genetics / Q000378:metabolism*
D027381:Liver-Specific Organic Anion Transporter 1; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3