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Comparative Study
. 2016 Jul;44(7):999-1004.
doi: 10.1124/dmd.115.069252. Epub 2016 Apr 20.

Expression Patterns of Organic Anion Transporting Polypeptides 1B1 and 1B3 Protein in Human Pediatric Liver

Margaret M S Thomson  1 , Ronald N Hines  1 , Erin G Schuetz  1 , Bernd Meibohm  2
Affiliations
Comparative Study

Expression Patterns of Organic Anion Transporting Polypeptides 1B1 and 1B3 Protein in Human Pediatric Liver

Margaret M S Thomson et al. Drug Metab Dispos. 2016 Jul.

Abstract

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.

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Figures

Fig. 1.
Fig. 1.
Representative Western blot analysis of OATP1B1 and OAT1B3 in pediatric liver specimens. Lane 1, positive control for OATP1B3; lane 2, molecular ladder; lane 3, positive control for OATP1B1; lanes 4–6, pediatric liver specimens.
Fig. 2.
Fig. 2.
Relative OATP1B protein expression (normalized to GAPDH) in pediatric liver for different age groups (group A, <3 months; group B, 3 months to <2 years; group C, 2 to <6 years; group D, 6–12 years), as follows: highly glycosylated OATP1B3 (A); core-glycosylated OATP1B3 (B); total (highly glycosylated and core-glycosylated) OATP1B3 (C); and OATP1B1 (D). Boxes represent the interquartile range, whiskers represent the 10th and 90th percentiles. The solid horizontal line in the box denotes the median, and the dotted line represents the mean of the data.
Fig. 3.
Fig. 3.
Relative OATP1B protein expression (normalized to GAPDH) in pediatric liver versus postnatal age. The x-axis is discontinuous, with ages less than 1 year shown as a fraction. Highly glycosylated OATP1B3 (A), core-glycosylated OATP1B3 (B), total (highly glycosylated and core-glycosylated) OATP1B3 (C), and OATP1B1 (D).
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