Hepatic GABAA receptor functional regulation during rat liver cell proliferation

Gamma aminohutyric acid (GAB A.) receptor tunctionaI status was artaIV se(l in pa It ial hcpatcctoIn ised.II'II). lead nitrate (LN) induced hyperplastic and N-nifrosodiethylantinc INDEAI treated nctplastic rat Iivers during peak DNA synthesis. The high-affinity I'HJGALA binding significantly decreased in PII and NDEi\ rats and the receptor affinity decreased in NDEA and increased in LN rats compared with control . in NDEA. displacement analysis of I'I IIGABA with muscimol showed loss of low-allinity site and a shill of high-allinity cite towards low-allinity . ' 1 he affinity sites shifted towards high-affinity in LN rats. 'file number of low-allinity 1'I Ilhicuc)lline receptors decreased cignilic:uttly in NDEA and I'll whereas it increased in LN rats. (ir\Bi\t receptor :gunist. unrscinrul. disc dependcnllyinhihilcd epidermal growth factor IEGI--) induced DNA synthesis :uul enhanced the tr:utsfnrnting grmvth )actor (Il I I'(il (tlI mediated DNA synthesis suppression in prim:uy hepalucvte cultures . Our results suggest that GABA,t reccjhtor act as an inhibitory signal fur hepatic cell prolifctatiun.

Gaba Receptor Gene Expression during Rat Liver Cell Proliferation and Its Function in Hepatocyte Cultures

The present thesis is an attempt to understand the role of GABA, GABAA and GABAB receptors in the regulation of liver cell proliferation using in vivo and in vitro models. The work also focuses on the brain GABAergic changes associated with normal and neoplastic cell growth in liver and to delineate its regulatory function. The investigation of mechanisms involving mitogenic models without cell necrosis may contribute our knowledge about both on cell growth, carcinogenesis, liver pathology and treatment. Objectives of the present study are, to induce controlled liver cell proliferation by partial hepatectomy and lead nitrate administration and uncontrolled cell proliferation by N-nitrosodiethylamine treatment in male Wistar rats, the changes in the content of GABA, GABAA,GABAB in various rat brain regions. To study the GABAA and GABAB receptor changes in brain stem, hypothalamus, cerebellum and cerebral cortex during the active cortex during the period of active DNA synthesis in liver of different experimental groups. The changes in GABAA and GABAB receptor function of the brain stem, hypothalamus and cerebellum play an important role sympathetic regulation of cell proliferation and neoplastic growth in liver. The decrease in GABA content in brain stem, hypothalamus and cerebellum during regeneration and neoplasia in liver. The time course of brain GABAergic changes was closely correlated with that of heptic DNA synthesis. The functional significance of these changes was further explored by studying the changes in GABAA and GABAB receptors in brain.

Adrenergic and serotonergic function in dna synthesis during rat liver regeneration and in hepatocyte cultures

The adult mammalian liver is predominantly in a quiescent state with respect to cell division. This quiescent state changes dramatically, however, if the liver is injured by toxic, infectious or mechanic agents (Ponder, 1996). Partial hepatectomy (PH) which consists of surgical removal of two-thirds of the liver, has been used to stimulate hepatocyte proliferation (Higgins & Anderson 1931). This experimental model of liver regeneration has been the target of many studies to probe the mechanisms responsible for liver cell growth control (Michalopoulos, 1990; Taub, 1996). After PH most of the remaining cells in the renmant liver respond with co-ordinated waves of DNA synthesis and divide in a process called compensatory hyperplasia. Hence, liver regeneration is a model of relatively synchronous cell cycle progression in vivo. In contrast to hepatomas, cell division is terminated under some intrinsic control when the original cellular mass has been regained. This has made liver regeneration a useful model to dissect the biochemical and molecular mechanisms of cell division regulation. The liver is thus, one of the few adult organs that demonstrates a physiological growth rewonse (Fausto & Mead, 1989; Fausto & Webber, 1994). The regulation of liver cell proliferation involves circulating or intrahepatic factors that are involved in either the priming of hepatocytes to enter the cell cycle (Go to G1) or progression through the cell cycle. In order to understand the basis of liver regeneration it is mandatory to define the mechanisms which (a) trigger division, (b) allow the liver to concurrently grow and maintain dilferentiated fimction and (c) terminate cell proliferation once the liver has reached the appropriate mass. Studies on these aspects of liver regeneration will provide basic insight of cell growth and dilferentiation, liver diseases like viral hepatitis, toxic damage and liver transplant where regeneration of the liver is essential. In the present study, Go/G1/S transition of hepatocytes re-entering the cell cycle after PH was studied with special emphasis on the involvement of neurotransmitters, their receptors and second messenger function in the control of cell division during liver regeneration

Comparative Studies on Arginase of the Liver of Some Vertebrates

The levels and kinetic properties of arginase of the liver of s vertebrates : the fish otifg trhinea e)n, ztyhmee b ias thi(gPhteerro ipnu aslls tph.e), 3t hmeasmqumirarles lin(F cuonmampabruilsuosnp teon tnhaantt oi)f tahned p tohiek iglootahter(Cmaspra s(pC.)atalarec sattulad)i,edth. eT fhreo ga c(tRivaintya greater than that of the frog. The activity ; its activity in the fish is far in the bat and highest in the goat. in the bat is the same as in other mammals. The Km of the enzyme is lowest partially purified enzyme of vertebrates. significant difference in the inhibitory effect of glyoxylic acid on the partially purified enzyme of vertebrates.

5-HT1A AND 5-HT2C RECEPTOR GENE EXPRESSION AND FUNCTIONAL REGULATION DURING RAT HEPATOCYTE PROLIFERATION AND APOPTOSIS

The work is an attempt to understand the role of 5-HT, 5-HT1A and 5-HT2C receptors in the regulation of liver cell proliferation using in vivo and in vitro models. The work also focuses on the brain serotonergic changes associated with hapatocyte proliferation and apoptosis to delineate its regulatory function. The investigation of mechanisms involving different models of hepatocyte proliferation contributes to our knowledge about serotonergic regulation of cell growth, apoptosis and carcinogenesis of liver. The study reveals that the alteration of the 5-HT1A and 5-HT2C receptor function and gene expression in the brain stem, cerebral cortex and hypothalamus play an important role in the sympathetic regulation of cell proliferation, neoplastic transformation and apoptosis. The functional balance between 5-HT1A and 5-HT2C receptor plays an important role in regulating hepatocyte proliferation, neoplastic transformation and hepatic apoptosis. The regulatory role of 5-HT1A and 5-HT2C receptor during neoplastic transformation and apoptosis could lead to possible therapeutic intervention in the treatment of cancers and have immense clinical importance.