CONTROL OF CELL GROWTH BY ALTERING CELL MEMBRANE POTENTIALS

摘要

Gamma aminobutyric acid (GABA) is a potent inhibitoryneurotransmitter that binds to hetero-oligomeric receptors in the mammalianbrain. Ina previous study, we documented specific GABA binding to isolated rathepatocyteswhich resulted in inhibition of hepatocyte proliferation. The purpose of thepresentstudy was to define the nature of hepatic GABA A receptors and document theirexpression during rapid liver growth (post-partial hepatectomy). Polymerasechainreactions (PCR) with gene-specific primers derived from published sequenceswereperformed with marathon-ready human and rat liver cDNA. Two GABA A receptorsubunit types (.beta.3 and .epsilon.) were expressed in the human liver andone (.beta.3) in the ratliver. PCR amplification of the human GABA A receptor .beta.3 subunit produceda singleproduct (m.w. 53-59 kDa). In the case of the .epsilon. subunit, two PCRproducts wereidentified. Following partial hepatectomy, GABA A receptor .beta.3 subunitexpressioninversely correlated with regenerative activity (r= -0.527, p=0.006). Inconclusion,these results indicate that in the human liver, GABA A receptors consist ofthe .beta.3 and .epsilon.subunit types whereas in the rat liver, only the .beta.3 subunit type isexpressed. Theresults also support the hypothesis that GABAergic activity serves to maintainhepatocytes in a quiescent state.