Developmental Changes in Hepatic Organic Cation Transporter OCT1 Protein Expression from Neonates to Children

作者:Hahn David; Emoto Chie; Vinks Alexander A; Fukuda Tsuyoshi*
来源:Drug Metabolism and Disposition, 2017, 45(1): 23-26.
DOI:10.1124/dmd.116.072256

摘要

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.

  • 出版日期2017-1