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Developmental Changes in Hepatic Organic Cation Transporter OCT1 Protein Expression from Neonates to Children
David Hahn1, Chie Emoto1, Alexander A Vinks1
1Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio (D.H., C.E., A.A.V., T.F); and Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio (C.E., A.A.V., T.F).
Insights
Organic cation transporter 1 (OCT1) protein expression increases significantly with age in children. This study reveals low OCT1 levels in neonates, impacting drug disposition and requiring further research.
Area of Science:
- Pharmacology
- Biochemistry
- Pediatrics
Background:
- Organic cation transporter 1 (OCT1) is crucial for drug metabolism.
- OCT1 activity is linked to its protein expression levels.
- Limited data exists on OCT1 expression in pediatric populations, especially neonates.
Purpose of the Study:
- To characterize OCT1 protein expression in liver samples from neonates, infants, and children.
- To understand the developmental changes in OCT1 expression from birth through adolescence.
Main Methods:
- Immunoblot analysis was used to quantify OCT1 protein levels.
- Liver samples were collected from various pediatric age groups, including neonates.
- OCT1 expression was normalized to glyceraldehyde-6-phosphate dehydrogenase (GAPDH).
Main Results:
- OCT1 protein was detected in the youngest neonates (postnatal days 1-2).
- OCT1 expression was significantly lower in neonates compared to older children (P < 0.01).
- A clear age-dependent increase in OCT1 expression was observed from birth to 8-12 years.
Conclusions:
- OCT1 expression demonstrates a significant age-dependent increase throughout childhood.
- These findings are vital for understanding OCT1-mediated drug disposition in infants.
- The study highlights the need to consider developmental changes in OCT1 for pediatric pharmacotherapy.
Abstract:
Organic cation transporter 1 (OCT1) plays an important role in the disposition of clinically important drugs, and the capacity of OCT1 activity is presumed to be proportional to the protein expression level in organ tissues. Knowledge of OCT1 protein expression in children, especially neonates and small infants, is currently very limited. Here, we report on the characterization of OCT1 protein expression in neonatal, infant, and pediatric liver samples performed using immunoblot analysis. OCT1 protein expression was detected in liver samples from neonates as early as postnatal days 1 and 2. This youngest group showed significantly lower OCT1 expression normalized by glyceraldehyde-6-phosphate dehydrogenase (values given as means ± S.D. in arbitrary units; 0.03 ± 0.02, n = 7) compared with samples from patients aged 3 to 4 weeks (0.08 ± 0.03, n = 5, P < 0.01), 3 to 6 months (0.23 ± 0.15, n = 7, P < 0.01), 11 months to 1 year (0.42 ± 0.32, n = 6, P < 0.01), and 8 to 12 years (1.00 ± 0.44, n = 7, P < 0.01). These data demonstrate an age-dependent increase in OCT1 expression from birth up to 8 to 12 years of age, and the findings of this study contribute to the understanding of OCT1 functional capacity and its effect upon the disposition of OCT1 substrates in neonates and small infants.
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