Hepatic GABA(A) receptor functional regulation during rat liver cell proliferation

Gamma aminobutyric acid (GABA(A)) receptor functional status was analysed i n partial hepatectomised (PH), lead nitrate (LN) induced hyperplastic and N -nitrosodiethylamine (NDEA) treated neoplastic rat livers during peak DNA s ynthesis. The high-affinity [H-3]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 [H-3]GABA with muscimol showed loss of low-affinity site and a shift of high-affinit y site towards low-affinity. The affinity sites shifted towards high-affini ty in LN rats. The number of low-affinity [H-3]bicuculline receptors decrea sed significantly in NDEA and PH whereas it increased in LN rats. GABA(A) r eceptor agonist, muscimol, dose dependently inhibited epidermal growth fact or (EGF) induced DNA synthesis and enhanced the transforming growth factor beta1 (TGF beta1) mediated DNA synthesis suppression in primary hepatocyte cultures. Our results suggest that GABA(A) receptor act as an inhibitory si gnal for hepatic cell proliferation. (C) 2001 Elsevier Science B.V. All rig hts reserved.