Hepatic GABA A receptor functional regulation during rat liver cell proliferation

Abstract

Gamma aminobutyric acid (GABA A) receptor functional status was analysed in partial hepatectomised (PH), lead nitrate (LN) induced hyperplastic and N-nitrosodiethylamine (NDEA) treated neoplastic rat livers during peak DNA synthesis. The high-affinity [ 3H]GABA binding significantly decreased in PH and NDEA rats and the receptor affinity decreased in NDEA and increased in LN rats compared with control. In NDEA, displacement analysis of [ 3H]GABA with muscimol showed loss of low-affinity site and a shift of high-affinity site towards low-affinity. The affinity sites shifted towards high-affinity in LN rats. The number of low-affinity [ 3H]bicuculline receptors decreased significantly in NDEA and PH whereas it increased in LN rats. GABA A receptor agonist, muscimol, dose dependently inhibited epidermal growth factor (EGF) induced DNA synthesis and enhanced the transforming growth factor β1 (TGFβ1) mediated DNA synthesis suppression in primary hepatocyte cultures. Our results suggest that GABA A receptor act as an inhibitory signal for hepatic cell proliferation.