L-Carnitine and creatine transporters, OCTN2 and CRT1, respectively, are located on the apical membrane of renal tubular epithelial cells. They are important for the concentrative reabsorption of L-carnitine and creatine, respectively, after their glomerular filtration in the kidney. In the current work, the ontogeny of L-carnitine and creatine transport by rat renal brush border membrane (BBM) has been studied.

BBM Vesicles (BBMV) were isolated from the kidney of newborn (1 day postpartum), suckling (16-18 days), weaning (30 days) and adult (2- and 7-month-old) Wistar rats. The animals were terminally anaesthetized with ether and humanely killed. BBMV were obtained using the method of Biber et al. (1981). L-[¹⁴C]carnitine or [¹⁴C]creatine uptake into BBMV was measured by a rapid filtration technique.

It was observed that BBMV of newborn Wistar rats transport L-carnitine and creatine and that the rate of transport of the two solutes increased with age, reaching a plateau at 1 month old. Kinetic studies revealed that the maximal rate of transport, V_max, increased with development from 6.4 ± 0.2 at 1 day old (n = 3) to 42.1 ± 2.4 at 2 months old (n = 3) for creatine, and from 0.8 ± 0.03 at 1 day old (n = 2) to 4.0 ± 0.08 at 1 month old (n = 8) for L-carnitine. However, no changes in K_m values (12 µM (n = 16) for creatine and 48 µM (n = 12) for L-carnitine) were observed. These observations suggest an increase in either the density or the turnover of transporters during ontogeny. Northern blot analysis revealed one transcript for OCTN2 of 3.7 kb and two for CRT1 of 3.2 kb and 4.9 kb. In all cases, the intensity of the bands were low at birth and increased throughout development, approaching maximum levels at 30 days of age.

In conclusion, transport activity and mRNA expression levels of L-carnitine and creatine are increased with age.

This work was supported by a grant from the Spanish Ministerio de Ciencia y Tecnología (DGICYT PM99-0121).