Identification of an acceptor system for gamma-aminobutyric acid on isolated rat hepatocytes.

gamma-Aminobutyric acid (GABA) is a potent inhibitory neurotransmitter which is synthesized by the enteric bacterial flora and delivered into portal venous blood. To determine whether the liver is likely to play an important role in regulating serum GABA levels, the uptake and metabolism of [3H]GABA by three populations of cells isolated from rat liver were studied. GABA was specifically taken up by hepatocytes but not by endothelial or Kupffer cells. Uptake by hepatocytes was saturable, as well as time and sodium dependent. At 0.5 degrees C, a temperature at which binding of GABA to the cell surface is considered to be the predominant component of the uptake process, the apparent affinity constant (Km) was 0.82 microM and a minimum value for binding velocity (Vmax) was 0.13 microM per min per 5 X 10(5) cells. Uptake of [3H]GABA by hepatocytes was markedly inhibited by excess unlabeled GABA (95%), alpha-aminoisobutyric acid (66%) and bicuculline (58%), but was inhibited much less by alanine (16%) and leucine (29%). These findings suggest that GABA binds specifically to the high affinity acceptor of the A amino acid transport system of rat hepatocytes. Impaired function of this transport system in liver failure could contribute to increased circulating levels of GABA.