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-aminobutyric acid receptor subunit types
in human and rat liver
Liver Diseases Unit, Departments of 1 Medicine and 2 Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada R3E 3P5
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 (
3 and
) were expressed in human liver and one
subunit type (
3) in rat liver. PCR amplification of the human
GABAA receptor
3-subunit produced a single product
(molecular mass 53-59 kDa). In the case of the
-subunit, two
PCR products were identified. After partial hepatectomy,
GABAA receptor
3-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
3- and
-subunit types, whereas in the rat liver only the
3-subunit type
is expressed. The results also support the hypothesis that GABAergic
activity serves to maintain hepatocytes in a quiescent state.
gamma-aminobutyric acid A receptor; hepatocytes; receptors; neurotransmitters
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