Received for publication April 12, 2005.
Revised June 9, 2005.
Accepted for publication June 9, 2005.

Uptake of L-carnitine and its Short-chain Ester Propionyl-L-carnitine in the Isolated Perfused Rat Liver

Abstract

Abstract Hepatic uptake of propionyl- (PLC) and L-carnitine (LC) was assessed with the impulse response (IR) technique in the single-pass perfused rat liver. The experiments involved a rapid injection (impulse) of a mixture of the radiolabeled test compound (propionyl- or L-carnitine) and a reference compound (sucrose) into portal vein inflow and collection and radiochemical analysis (response) of the venous outflowing perfusate samples. The impulse injection was made in the presence of increasing unlabeled background concentrations of PLC (0-50 µM) or LC (50-500 µM) perfusing the liver. For LC the hepatic uptake was minimal or negligible, whereas for PLC the hepatic influx clearance was found to be low (0.095 ml · sec^-1 equivalent to 5.7 ml · min^-1) relative to the perfusate flow rate (30 ml · min^-1). When background concentrations of PLC were increased (from 1 to 50 µM) the influx clearance was reduced in a concentration-dependent behaviour, indicating partial saturation of the entry of compound into hepatocytes. PLC was taken up into hepatocytes via a unidirectional transport process with negligible efflux. The hepatic uptake of PLC was significally reduced in the presence of unlabeled LC (500 µM) indicating an inhibition of the sinusoidal membrane transport of PLC by LC. The study demonstrated the sinusoidal membrane is a permeability barrier to the entry of PLC and LC into hepatocytes and it is the site of a common carrier mediated transporter for both compounds.

Key words: L-carnitine, impulse response, liver, perfused, propionyl-L-carnitine, uptake