Identification of gamma-aminobutyric acid receptor subunit types in human and rat liver.

Abstract

GABA is a potent inhibitory neurotransmitter that binds to heterooligomeric receptors in the mammalian brain. In a previous study, we documented specific GABA binding to isolated rat hepatocytes that resulted in inhibition of hepatocyte proliferation. The purpose of the present study was to define the nature of hepatic GABA(A) receptors and to document their expression during rapid liver growth (after partial hepatectomy). PCRs with gene-specific primers derived from published sequences were performed with Marathon-ready human and rat liver cDNA. Two GABA(A) receptor subunit types (beta3 and epsilon) were expressed in human liver and one subunit type (beta3) in rat liver. PCR amplification of the human GABA(A) receptorbeta3-subunit produced a single product (molecular mass 53-59 kDa). In the case of the epsilon-subunit, two PCR products were identified. After partial hepatectomy, GABA(A) receptorbeta3-subunit expression inversely correlated with regenerative activity (r = -0.527, P = 0.006). In conclusion, these results indicate that in the human liver GABA(A) receptors consist of the beta3- and epsilon-subunit types, whereas in the rat liver only the beta3-subunit type is expressed. The results also support the hypothesis that GABAergic activity serves to maintain hepatocytes in a quiescent state.