Ontogeny profile of hepatic uptake transporters in rats based on uptake activity, protein expression, and mRNA expression levels
Percentages represent expression/activity relative to adult levels.
| Onset of Activity and/or Expression | Adult Levels Reached | Age-Related Changes in Activity/Expression | Comments | References | |
|---|---|---|---|---|---|
| NTCP | |||||
| Uptake activity | 2 days: 10%–20% | 29 days | Increased progressively | Adult age: 55 days. Fetal development: NR Substrate: 3H-taurocholate. Strain and sex: Wistar (M). Matrix: hepatocytes in suspension. Methods: liquid scintillation counting | Fattah et al. (2015) |
| mRNA expression | Fetal development: <36% | Birth: 75% | Increased rapidly during fetal development | Adult age: NR. Birth–adult: NR. Strain and sex: Wistar (F). Methods: RT-PCR | St-Pierre et al. (2004) |
| OCT1 | |||||
| Uptake activity | 1 day: 130% | 1 days | Peaked at 7 days (150%) | Adult age: 49 days. Fetal development: NR. Substrate: [3H]-1-methyl-4-phenylpyridinium. Strain and sex: Wistar (M/F). Matrix: liver slices. Methods: liquid scintillation counting | Martel et al. (1998) |
| CNT1 | |||||
| Protein expression | Fetal development: 35%–50% | 21 days: 70% | Increased slowly | Adult age: NR. Strain and sex: Wistar (F). Methods: Western blotting | del Santo et al. (2001) |
| CNT2 | |||||
| Protein expression | Fetal development: 40%–70% | 21 days: 70% | Increased slowly | Adult age: NR. Strain and sex: Wistar (F). Methods: Western blotting | del Santo et al. (2001) |
| mRNA expression | Fetal development: 20% | 45 days | Increased slowly | Adult age: 45 days. Strain and sex: Wistar (F). Methods: Northern blotting | del Santo et al. (2001) |
| CNT1/2 | |||||
| Uptake activity | Fetal development: 300% | Fetal development | Decreased rapidly in neonates (200%) | Adult age: NR. Substrate: uridine. Strain and sex: Wistar (F). Matrix: hepatocytes in suspension. Methods: Radioactivity | del Santo et al. (2001) |
| SNAT1 | |||||
| Protein expression | Fetal development: 300%–500% | Fetal development | Decreased rapidly in neonates (200%) | Adult age: NR. Strain and sex: Sprague Dawley (M/F). Methods: immunoblotting | Weiss et al. (2005) |
| OATP1A1 | |||||
| Protein expression | NR | NR | Decreased in elderly M: 800 days (40%). F: 800 days (10%) | Adult age: 60 days. Fetal development–adult: NR. Strain and sex: Sprague Dawley (M/F). Methods: Western blotting | Hou et al. (2014) |
| mRNA expression | Fetal development: <2% | M: 35 days (78%). F: 35 days (44%) | Increased slowly then decreased in elderly | Adult age: 56–70 days. Strain and sex: Sprague Dawley (M/F). Methods: RT-PCR | St-Pierre et al. (2004); Macias et al. (2011); Hou et al. (2014); Kawase et al. (2015) |
| OATP1A4 | |||||
| Protein expression | Birth: 15%–40% | 28 days: 40%. M: 25 days. F: 30 days | Increased slowly then decreased in elderly or increased progressively with no changes after 25 days | Adult age: 60 days. Strain and sex: Sprague Dawley (M/F). Methods: Western blotting | Guo et al. (2002); Hou et al. (2014) |
| mRNA expression | Fetal development: <2%; Birth: 30%–76% | M: 10–35 days (65%). F: 25–35 days (20%) | Interstudy variability: increased slowly then decreased in elderly, or increased rapidly (M) vs. progressively (F) | Adult age: 45–60 days. Strain and sex: Sprague Dawley (M/F). Methods: RT-PCR, branched DNA signal amplification assay | Guo et al. (2002); St-Pierre et al. (2004); Macias et al. (2011); Hou et al. (2014) |
| OATP1A5 | |||||
| mRNA expression | Fetal development: <30% | 35 days: 65%–70% | Increased slowly then decreased in elderly | Adult age: 60 days. Strain and sex: Sprague Dawley (M/F). Methods: RT-PCR | Hou et al. (2014) |
| OATP1B2 | |||||
| Uptake activity | 2 days: 25% | 55 days | Some decrease between birth and weaning (10% at 3 wk) then rapid increase to adult values | Adult age: 55 days. Fetal development: NR. Substrate: sodium fluorescein. Strain and sex: Wistar (M). Matrix: hepatocytes in suspension. Methods: fluorescence spectrometry | Fattah et al. (2015) |
| Protein expression | NR | M: 28 days (50%). F: 28 days (70%) | Increased slowly then decreased in elderly | Adult age: 60 days Fetal development – 28 days: NR Strain and sex: Sprague Dawley (M/F) | Hou et al. (2014) |
| mRNA expression | Fetal development: <10%; birth: 20% | M: 35 days (78%). F: 60 days | M: Increased progressively. F: Increased slowly. Decreased in elderly | Adult age: 45–60 days. Strain and sex: Sprague Dawley and Wistar (M/F). Methods: RT-PCR, branched DNA signal amplification assay | Li et al. (2002); St-Pierre et al. (2004); Macias et al. (2011); Hou et al. (2014) |
| OATP2B1 | |||||
| mRNA expression | Fetal development: <16% | Birth: 20% | NR | Adult age: NR. Birth–adult: NR. Strain and sex: Wistar (M/F). Methods: RT-PCR | St-Pierre et al. (2004) |
| OATP4A1 | |||||
| mRNA expression | Fetal development: 255% | Fetal development | Increased rapidly at birth (310%) | Adult age: NR. Birth–adult: NR. Strain and sex: Wistar (M/F). Methods: RT-PCR | St-Pierre et al. (2004) |
F, female; M, male; NR, not reported; RT-PCR, reverse-transcriptase polymerase chain reaction.