Identification of γ-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 GABAA 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 GABAA receptor subunit types (β3 and ε) were expressed in human liver and one subunit type (β3) in rat liver. PCR amplification of the human GABAA receptorβ3-subunit produced a single product (molecular mass 53–59 kDa). In the case of the ε-subunit, two PCR products were identified. After partial hepatectomy, GABAA receptorβ3-subunit expression inversely correlated with regenerative activity ( r = −0.527, P = 0.006). In conclusion, these results indicate that in the human liver GABAA receptors consist of the β3- and ε-subunit types, whereas in the rat liver only the β3-subunit type is expressed. The results also support the hypothesis that GABAergic activity serves to maintain hepatocytes in a quiescent state.