A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 45/00 (2006.01) A61K 38/17 (2006.01) A61K 38/26 (2006.01)
Patent
CA 2347350
Gamma aminobutyric acid (GABA) is a potent inhibitory neurotransmitter that binds to hetero-oligomeric receptors in the mammalian brain. In a previous study, we documented specific GABA binding to isolated rat hepatocytes which resulted in inhibition of hepatocyte proliferation. The purpose of the present study was to define the nature of hepatic GABA A receptors and document their expression during rapid liver growth (post-partial hepatectomy). Polymerase chain reactions (PCR) with gene-specific primers derived from published sequences were performed with marathon-ready human and rat liver cDNA. Two GABA A receptor subunit types (.beta.3 and .epsilon.) were expressed in the human liver and one (.beta.3) in the rat liver. PCR amplification of the human GABA A receptor .beta.3 subunit produced a single product (m.w. 53-59 kDa). In the case of the .epsilon. subunit, two PCR products were identified. Following partial hepatectomy, GABA A receptor .beta.3 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 .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 maintain hepatocytes in a quiescent state.
Minuk Gerald Y.
Battison Williams Dupuis
The University Of Manitoba
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