Uptake and catabolism of gamma-aminobutyric acid by the isolated perfused rat liver.
Serum concentrations of gamma-aminobutyric acid (GABA) are increased in liver failure, possibly because of decreased hepatic GABA catabolism. To study in detail the role of the liver in GABA metabolism, uptake and catabolism of GABA by isolated perfused liver from normal rats and rats with galactosamine- or carbon tetrachloride-induced liver failure were measured. Hepatic GABA uptake was almost complete at GABA concentrations of up to 10 microM and approached saturation at a concentration of 50 microM. The apparent affinity of hepatic GABA uptake was 38 microM and the apparent maximal velocity was 158 nmol/g.min. Hepatic GABA uptake was sodium-dependent. gamma-Aminobutyric acid taken up by the liver was rapidly catabolized as measured by 14CO2 formation from [U-14C]GABA. Aminooxyacetic acid, a GABA transaminase inhibitor, completely and irreversibly inhibited hepatic GABA catabolism and thereby also inhibited hepatic GABA uptake. Although uptake of GABA by livers of carbon tetrachloride- or galactosamine-treated rats was decreased (apparent maximal velocity, 103 and 98 nmol/g.min, respectively), at physiologic GABA concentrations in the perfusate GABA uptake and catabolism was not different from that of untreated controls. The observed impairment of hepatic GABA uptake or catabolism by the diseased liver would be expected to contribute to increased GABA levels in peripheral blood plasma in liver failure. However, the magnitude of the observed impairment would be insufficient to account for a 10-fold increase in such levels.
Ferenci
P
P
First Department of Gastroenterology and Hepatology, University of Vienna, Austria.
Stehle
T
T
Ebner
J
J
Schmid
R
R
Häussinger
D
D
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D002851:Chromatography, High Pressure Liquid; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D010477:Perfusion; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000493:pharmacokinetics*
D005680:gamma-Aminobutyric Acid