A. Mancinelli et al., DISPOSITION OF L-CARNITINE AND ACETYL-L-CARNITINE IN THE ISOLATED-PERFUSED RAT-KIDNEY, The Journal of pharmacology and experimental therapeutics, 274(3), 1995, pp. 1122-1128
The isolated perfused rat kidney was used to investigate the regulatio
n, specificity and concentration-dependence of the renal tubular dispo
sition of L-carnitine (LC) and its ester, acetyl-L-carnitine (ALC). Tr
itiated markers were used to study the renal disposition of LC and ALC
and HPLC was used to purify H-3-LC and H-3-ALC before radiochemical a
nalysis. At perfusate concentrations comparable to those found in plas
ma in vivo (50 mu M for LC and 5 mu M for ALC), the renal clearance of
both analogues was substantially less than GFR (P < .05) which, in vi
ew of their negligible binding to perfusate proteins, is indicative of
extensive reabsorption. During the first 20 min of perfusion, the per
cent tubular reabsorption (%TR) of LC and ALC was 94 +/- (SD) 2.6% and
97 +/- 0.6%, respectively. The extent of H-3-ALC and H-3-LC enrichmen
t of perfusate in experiments with H-3-LC and H-3-ALC, respectively, p
rovided evidence for the capability of the rat kidney to acetylate LC
and deacetylate ALC. In addition, a portion of renally generated H-3-A
LC and H-3-LC was found to undergo leakage into renal tubules and esca
pe subsequent reabsorption. It was also found that the %TR of both com
pounds decreased substantially when the perfusate concentration was in
creased above endogenous levels; each compound was capable of decreasi
ng the %TR of the other; and trimethylamine-N-oxide, a metabolite of L
C, had no significant effect on the renal handling of the carnitine de
rivatives.