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

GABA is a potent inhibitory neurotransmitter that binds to heterooligomeric receptors in the mammalian brain. In a previous study, we documented speci fic GABA binding to isolated rat hepatocytes that resulted in inhibition of hepatocyte proliferation. The purpose of the present study was to define t he nature of hepatic GABAA receptors and to document their expression durin g rapid liver growth (after partial hepatectomy). PCRs with gene-specific p rimers derived from published sequences were performed with Marathon-ready human and rat liver cDNA. Two GABAA receptor subunit types (beta 3 and epsi lon) were expressed in human liver and one subunit type (b3) in rat liver. PCR amplification of the human GABA(A) receptor beta 3-subunit produced a s ingle product (molecular mass 53-59 kDa). In the case of the epsilon-subuni t, two PCR products were identified. After partial hepatectomy, GABA(A) rec eptor beta 3-subunit expression inversely correlated with regenerative acti vity (r = 0.527, P = 0.006). In conclusion, these results indicate that in the human liver GABAA receptors consist of the beta 3- and epsilon-subunit types, whereas in the rat liver only the beta 3-subunit type is expressed. The results also support the hypothesis that GABAergic activity serves to m aintain hepatocytes in a quiescent state.