Table 2.
Human Ontogeny Data of Membrane Transporters in Intestine, Liver, and Kidney Highlighted in This Article GA indicates gestational age; TM50, age at which half of the adult value is reached.
| Membrane Transporter, Protein Name (Gene Name) | Types of Ontogeny Data Available | Reported Ontogeny Pattern | Reference |
|---|---|---|---|
| Intestinal transportersa | |||
| P-gp (ABCB1) | Gene expression | Overall, the mRNA levels in neonates and infants were comparable to those in adults | Mizuno et al,20 Fakhouryetal,21,22 Miki et al,24 van Kalken et al,25 Mooij et al26 |
| BCRP (ABCG2) | Immunohistochemistry | BCRP distribution was similar in fetal (5.5–28 wk of gestation) and adult samples | Konieczna et al27 |
| MRPI (ABCC1) | Immunohistochemistry | MRPI distribution was similar in adults and fetal samples (9–28 wk of gestation) | Konieczna et al27 |
| MRP2 (ABCC2) | Gene expression | mRNA level was stable from neonates to adults | Mooij et al26 |
| OATP2B1 (SLCO2B1) | Gene expression | mRNA level was higher in neonates than in adults | Mooij et al26 |
| PEPT1 (SLCI5A1) | Gene expression | mRNA was slightly lower in neonates than in older counterparts | Mooij et al28 |
| Liver transporters | Immunohistochemistry | Tissue distribution was relatively stable from preterm neonates to adolescents | Mooij et al28 |
| OCT1 (SLC22A1) | Gene expression | Transcript levels in pediatric livers were comparable with those in adults | Hayashi et al36 |
| Western blot | Age-dependent increase in OCT1 protein expression from birth up to 8–12 y | Hahn et al37 | |
| Quantitative proteomics | Age-dependent increase in protein expression level; TM50 was approximately 6 mo | van Groen et al,33 Prasad et al34 | |
| OATP1B1 (SLCO1B1) | Gene expression | mRNA expression of OATP1B1 in fetal liver was 20-fold lower than that in adults. Neonates and infants have even lower levels than fetus (500-fold and 90-fold lower than adults, respectively) | Mooij et al26 |
| Quantitative proteomics | van Groen et al reported higher protein expression in fetal livers compared with that in term neonates. The protein expressions in infants to adults were similar. Genetic polymorphism was not associated with expression levels in this study. Prasad et al reported that when all samples were considered, no age-dependent changes in the protein expression was found. Protein levels were higher in *IAI*IA > 1-y-old cohort than the 0- to 12-mo group | van Groen et al,33 Prasad et al34 | |
| OATP1B3 (SLCO1B3) | Gene expression | mRNA levels in fetus, neonates and infants were lower than that in adults | Mooij et al26 |
| Quantitative proteomics | No age-dependent changes were found in van Groen et al; age-dependent increase reported in Prasad et al with TM50 approximately 6 mo | van Groen et al,33 Prasad et al34 | |
| OATP2B1 (SLCO2B1) | Gene expression | mRNA level was significantly higher in adult liver compared with that in fetus (GA 18–23 weeks) | Sharma et al39 |
| Quantitative proteomics | Comparable protein expression levels in livers from fetus to adults | van Groen et al,33 Prasad et al3440 | |
| NTCP (SLCIOAI) | Gene expression | mRNA level was low in fetal liver compared with adults | Sharma et al,39 Chen et al41 |
| Western blot | Relative expression was stable in livers samples from neonates and adults | Yanni et al42 | |
| Quantitative proteomics | Prasad et al reported stable protein expression from neonates to adults, van Groen et al showed that protein expression was significantly lower in fetuses than in term neonates, infants, children, and adults | van Groen et al,33 Prasad et al34 | |
| P-gp (ABCB1) | Gene expression | Detected in fetal liver; mRNA level increased rapidly during first 12 mo of life in infants | Mooij et al26 |
| Western blot | No significant differences in the relative protein expression from 0.3 to 12 y old | Tang et al43 | |
| Quantitative proteomics | Protein level increase from fetus to adults with TM50 approximately 2.9 y old | van Groen et al,33 Prasad et al34 | |
| MRP2 (ARCC2) | Gene expression | mRNA level increased; levels in fetal, neonatal, and infant livers were substantially lower than that in older children up to 12 y old | Mooij et al,26 Klaassen and Aleksunes44 |
| Quantitative proteomics | van Groen et al reported that MRP2 level was much lower in fetal and term newborn livers than that in adults. Prasad et al found no age-dependent changes | van Groen et al,33 Prasad et al34 | |
| MRP3 (ABCC3) | Gene expression | mRNA level was lower in fetal livers than that in adults | Sharma et al39 |
| Quantitative proteomics | van Groen et al reported that protein abundance was lower in fetus and term neonates than in adults. In Prasad et al, lower protein abundance was found in infants and adolescents than adults. | van Groen et al,33 Prasad et al34 | |
| MRP1 (ABCC1) | Quantitative proteomics | Protein levels were lower in fetus and term neonates than adults | van Groen et al33 |
| MRP4 {ABCC4) | Gene expression | No age-dependent changes in mRNA level | Sharma et al39 |
| MRP6 (ABCC6) | Gene expression | mRNA level increase from neonates to older children and adults | Klaassen and Aleksunes44 |
| BCRP (ABCG2) | Immunohistochemistry Gene expression | Detected in fetus as young as GA 5.5 weeks mRNA level was lower in fetal livers than in adults | Konieczna et al27 Sharma et al,39 Klaassen and Aleksunes44 |
| Quantitative proteomics | Stable across age groups from fetus to adults but age-dependent decrease observed in fetal and newborn cohorts | van Groen et al,33 Prasad et al34 | |
| BSEP (ABCB11) | Quantitative proteomics | Significantly lower in fetal livers compared with that in adults; no age-dependent changes after birth | van Groen et al,33 Prasad et al34 |
| MATE1 (SLC47A1) | Gene expression | mRNA showed age-dependent increase | Klaassen and Aleksunes44 |
| Quantitative proteomics | No age-dependent changes in protein abundance | Prasad et al34 | |
| GLUTI (SLC2A1) | Quantitative proteomics | Protein abundance was high in fetus and lower in other age groups | van Groen et al33 |
| MCTI (SLC16A1) | Quantitative proteomics | No age-dependent changes in protein abundance | van Groen et al33 |
| Kidney transporters | |||
| BCRP (ABCG2) | Gene expression | mRNA level was higher in term neonates than older counterparts | Cheung et al46 |
| Quantitative proteomics | No age-dependent changes in protein abundance | Cheung et al46 | |
| MATE1 (SLC47A1) | Gene expression | No age-dependent changes in mRNA level | Cheung et al46 |
| Quantitative proteomics | No age-dependent changes in protein abundance | Cheung et al46 | |
| MATE2-K (SLC47A2) | Gene expression | mRNA level was lower in term newborns than in adults | Cheung et al46 |
| Quantitative proteomics | No age-dependent changes in protein abundance | Cheung et al46 | |
| MRP2 (ABCC2) | Gene expression | No age-dependent changes in mRNA level | Cheung et al46 |
| MRP4 (ABCC4) | Gene expression | No age-dependent changes in mRNA level | Cheung et al46 |
| Immunohistochemistry | Proper localization observed in renal cortical fetal sample as early as GA 27 wk | Cheung et al46 | |
| URAT1 (SLC22A12) | Gene expression | mRNA levels increased with age from term newborn to adults | Cheung et al46 |
| Quantitative proteomics | Protein levels increased with age from term newborn to adults | Cheung et al46 | |
| P-gp (ABCB1) | Immunohistochemistry | Localization detected as early as end of first trimester of fetal life | van Kalken et al25 |
| Gene expression | mRNA levels were lower in preterm newborns, term newborns, and infants compared with older counterparts | Cheung et al46 | |
| Quantitative proteomics | Protein levels increased with age with TM50 approximately 1 mo | Cheung et al46 | |
| GLUT2 (SLC2A2) | Gene expression | No age-dependent changes in mRNA level | Cheung et al46 |
| Quantitative proteomics | No age-dependent changes in protein abundance | Cheung et al46 | |
| OATI (SLC22A6) | Gene expression | mRNA level increased with age | Cheung et al46 |
| Quantitative proteomics | Protein abundance increased with age. TM50 was approximately 5 mo | Cheung et al46 | |
| OAT3 (SLC22A8) | Gene expression | mRNA level increased with age | Cheung et al46 |
| Quantitative proteomics | Protein abundance increased with age. TM50 was approximately 8 mo | Cheung et al46 | |
| OCT2 (SLC22A2) | Gene expression Quantitative proteomics | mRNA level increased with age Protein expression increased with age. TM50 was approximately 1 mo | Cheung et al46 Cheung et al46 |
a
See Brouwer et al for a more detailed review.14