Ontogeny of Na+/l-carnitine transporter and of γ-trimethylaminobutyraldehyde dehydrogenase and γ-butyrobetaine hydroxylase genes expression in rat kidney

The kidney synthesizes l-carnitine and reabsorbs it via the Na+/l-carnitine cotransporter OCTN2. This study investigates the ontogeny of OCTN2, γ-trimethylaminobutyraldehyde dehydrogenase (TMABA-DH) and γ-butyrobetaine hydroxylase (BBH) in rat kidneys. Foetuses, newborn, suckling, weaning and adult rats were used. The apical membranes of foetal and newborn rat kidneys express OCTN2 transport activity, which is up-regulated by age. Maturation significantly increased the Vmax of this transport system without changing the apparent Kt, which excludes a maturation-related expression of different transporter isoforms. Northern analysis showed a 3.7 kb transcript for OCTN2 in all the ages tested. Northern and RT-PCR assays revealed that maturation increased renal expression of OCTN2 mRNA. Foetuses express TMABA-DH mRNA and this expression increased during postnatal life. BBH mRNA, however, was detected during the suckling period onwards and its abundance was not changed significantly by maturation. This study reports for the first time that, in rat kidneys: (i) an apical OCTN2 transporter is active in rat foetuses, (ii) ontogeny up-regulates OCTN2 activity by increasing the density and/or turnover of the transporters, (iii) the maturation-related changes in OCTN2 are in part mediated by transcriptional mechanism(s) and (iv) the expression of both, TMABA-DH and BBH mRNA is ontogenically regulated. Some of these results were published as an abstract (García-Delgado et al., 2003).