Enhanced uptake of carnitine by perfused rat liver following starvation.
Previously, the release of carnitine from the perfused rat liver was found to be protein-mediated, dependent on the nutritional state but not on metabolic energy. Further, it was shown to exceed the physiological demand by about 10-fold (Sandor et al. (1985) Biochim. Biophys. Acta 835, 83-91). In the present study the uptake of carnitine by perfused rat liver has been investigated. The liver tissue and the perfusate were in equilibrium when the carnitine concentration in the perfusate was close to 45 microM, physiological in the rat plasma. Under this condition, when no net carnitine transport occurred, an unidirectional uptake of L-[3H]carnitine was observed. Quantitatively, the uptake rate was 355 +/- 60 (S.D.) nmol/h per 100 g body weight at 45-50 microM perfusate concentration. This uptake capacity balances the previously reported excessive release (Sandor et al., op. cit.). On this basis we propose that a futile release/uptake cycle operates in carnitine transport across the liver cell membrane. Liverse of 24-h starved rats took up L-[3H]carnitine at 56% higher rate from the perfusate (75 microM) than livers of fed rats. Kinetic analysis revealed that fasting caused a decrease in Km value from 4.22 mM to 2.59 mM, whereas Vmax remained practically unchanged, average 0.95 mumol/min per 100 g body weight. D-[3H]Carnitine was transported at the same rate as L-carnitine and underwent the effect of fasting as well. The uptake was partially inhibited by 1 mM 2,4-dinitrophenol and 5 mM KCN, showing its dependency on metabolic energy. If Li+ replaced Na+ a strong inhibitory effect (to 20% of control) was observed, which suggests a co-transport of carnitine with Na+. Mersalyl, an SH reagent, had no effect on the uptake, whereas it practically abolished the release of carnitine from the perfused livers. This observation suggests that the inward and outward transport of carnitine are mediated by two different proteins.
D019297:2,4-Dinitrophenol; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002331:Carnitine / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D005215:Fasting; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008634:Mersalyl / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002712:Chlorides; D004140:Dinitrophenols; D010042:Ouabain; D008634:Mersalyl; D008094:Lithium; D018021:Lithium Chloride; D011190:Potassium Cyanide; D019297:2,4-Dinitrophenol; D002331:Carnitine