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


CONCLUSIONS
These findings suggest a downregulation of OCTN2 at the renal level, in the presence of high levels of carnitine.
Gómez-Amores
Lucía
L
Department of Physiology and Zoology, Faculty of Pharmacy, University of Seville, E-41012 Seville, Spain.
Mate
Alfonso
A
Vázquez
Carmen M
CM
D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D002331:Carnitine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002352:Carrier Proteins / Q000378:metabolism; D004334:Drug Administration Schedule; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D027701:Organic Cation Transport Proteins; D009994:Osmolar Concentration; D051381:Rats; D011921:Rats, Inbred WKY; D000074058:Solute Carrier Family 22 Member 5; D013997:Time Factors; D014463:Ultrasonography
D002352:Carrier Proteins; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine