L-carnitine transport in kidney of normotensive, Wistar-Kyoto rats: effect of chronic L-carnitine administration.

PURPOSE

To examine the effect of long-term administration of L-carnitine on L-carnitine transport in renal brush-border membrane vesicles (BBMVs) from normotensive, Wistar-Kyoto rats.

METHODS

Rats (n = 20) were orally administered 0.2 g carnitine/kg body weight per day for a total period of 8 weeks. Kinetic parameters of L-carnitine uptake were calculated by non-linear regression, and the relative abundance of the carnitine transporter, OCTN2, was determined by Western blot analysis.

RESULTS

Initial rates and maximal overshoot levels of Na+-dependent L-carnitine transport were significantly reduced in BBMVs from L-carnitine-treated rats compared with untreated animals. Similarly, the maximal transport rate (Vmax) of OCTN2 was lower in treated rats. However, no differences were observed in the Michaelis constant (Km) or the diffusion constant (Kd) between the two groups of animals. The amount of OCTN2 protein was also decreased in L-carnitine-fed rats, this reduction being similar to that of the Vmax. These results were accompanied by an increase in the serum levels and also in the renal excretion of both free and esterified carnitine in treated rats, indicating that the long-term administration of L-carnitine leads to increased renal carnitine clearance.

CONCLUSION

These findings suggest a downregulation of OCTN2 at the renal level, in the presence of high levels of carnitine.