Rat Liver Cell Nuclei Research Articles

Investigation of nuclear DNA content and cell cycle phases in rat liver cells under chlorpromazine administration

Hepatotoxicity of antipsychotic drugs remains an urgent problem of modern medicine. Therefore, the purpose of the study was to investigate the nuclear DNA content and cell cycle phases of rat liver cells under Сhlorpromazine administration at doses ranging from 3.5 mg/kg to 28 mg/kg for 30 and 60 days. The study was conducted on 60 sexually mature female rats. Chlorpromazine was administered once daily for 30 and 60 days at doses of 3.5 mg/kg, 7 mg/kg, 14 mg/kg, 21 mg/kg and 28 mg/kg. The DNA content in the nuclei of rat liver cells was determined by flow cytometry. Cytological analysis of cells was performed using FloMax software (Partec, Germany), where the percentage of nuclei in the G0G1 interval of the cell cycle, in the S phase, G2M interval, and the apoptosis index – SUB-G0G1 area on DNA histograms were determined. Statistical processing of the results was performed using the Mann-Whitney U test. The results of the study showed that Сhlorpromazine has a dose-dependent hepatotoxic effect: with an increase in the dose of this drug in rats from 7 to 28 mg/kg, the percentage of fragmented nuclei in liver tissue significantly increased, which is a sign of hepatocyte death by apoptosis. It was found that Сhlorpromazine at a dose of 3.5 mg/kg did not increase hepatocyte apoptosis, while at a dose of 21 and 28 mg/kg the drug showed the highest hepatotoxicity, increasing the level of apoptosis by 1.9 and 2.1 (p˂0.05) times, respectively. The hepatotoxic effect is enhanced by the use of Сhlorpromazine for 60 days, which is manifested in a significant increase in hepatocyte nuclear DNA fragmentation, which, in our opinion, should be taken into account when conducting long-term therapy in patients.

Phospholipids and cholesterol of liver nuclei during artificial hypobiosis of rats

The contents of lipids in the tissue and the nuclei of liver cells during artificial hypobiosis, as well as in the nuclei of liver cells for 3 days after the cessation of cooling in rats, were studied. In the artificial hypobiosis and in the state of normothermia 24 h after the cessation of cooling, the total phospholipid content of the liver cell nuclei increased by 20% due to minor phospholipids. The levels of sphingomyelin, phosphatidylinositol, phosphatidylserine, cardiolipin, and lysophosphatidylcholine were doubled in hypobiosis and then nonmonotonically returned to the normal level within 72 h. In the state of artificial hypobiosis, the levels of fatty acids, cholesterol, and diglycerides increased by 30–40%. The state of artificial hypobiosis did not affect the level of lipids in the liver tissue of Wistar rats. The increase of the lipid content in the liver cell nuclei of Wistar rats indicates the important role of lipids in functions of the nucleus when the energy supply and protein synthesis are inhibited under conditions of artificial hypobiosis.

Phosphatidic acid metabolism in rat liver cell nuclei

The aim of the present research was to analyze the pathways for phosphatidic acid metabolism in purified nuclei from liver. Lipid phosphate phosphatase, diacylglycerol lipase, monoacylglycerol lipase and PA-phospholipase type A activities were detected. The presence of lysophosphatidic acid significantly reduced DAG production while sphingosine 1-phoshate and ceramide 1-phosphate reduced MAG formation from PA. Using different enzymatic modulators (detergents and ions) an increase in the PA metabolism by phospholipase type A was observed. Our findings evidence an active PA metabolism in purified liver nuclei which generates important lipid second messengers, and which could thus be involved in nuclear processes such as gene transcription.

Influence of distamycin A on the methylation, extraction, and formation of UV-inducible DNA-protein cross links of histone H1 in the interphase nuclei of rat liver cells

Incubation in vitro of rat liver nuclei in the presence of S-adenosyl[methyl-(3)H]methionine ([(3)H] SAM) leads to incorporation of the radioactive label not only into core-histones H3 and H4, but also into linker histone H1. Addition of distamycine A to the incubation medium stimulates label incorporation into histone H1 ~ in 6 times and into histone H3 ~ in 2 times. The presence of distamycine facilitates histone H1 extraction by polyglutamic acid (poly(Glu)) and decreases of UV-induced DNA-histone cross-links formation. These effects give evidence of weakening of H1-chromatin interaction by distamycin to be results of histone H1 position change relative to nucleosome and(or) disturbance of histones H1-H3 interactions so as these histones are exposed to additional methylation.

Uptake of Cr (VI) and Cr (III)–GSH complex across rat liver cell nuclei

Cr (VI) is a known carcinogen that readily crosses the cellular membrane and is then reduced by intracellular reductants such as reduced glutathione (GSH) to Cr (III), forming various reactive intermediate compounds (Ding and Shi, 2002). The interaction of Cr (VI) and GSH is known to be one of the causes of DNA damage in vitro (Mazzer et al., 2007). This study investigates the occurrence of Cr (III)-GSH in freshly isolated rat hepatocytes incubated with Cr (VI), and the uptake of Cr (VI) and Cr (III)-GSH complex across rat liver cell nuclei. Cr (III)-GSH complex was synthesised by the method of Levina et al. (2003), and its formation confirmed by liquid chromatography-mass spectrometry (LC-MS).

Expression of Hepatic UDP-Glucuronosyltransferase 1A1 and 1A6 Correlated with Increased Expression of the Nuclear Constitutive Androstane Receptor and Peroxisome Proliferator-Activated Receptor α in Male Rats Fed a High-Fat and High-Sucrose Diet

Rats that consumed a high-fat and high-sucrose (HF1) diet or a high-fat (HF2) diet developed hepatic steatosis. The alteration in nutritional status affected hepatic cytochrome P450 and UDP-glucuronosyltransferase (UGT) levels. Messenger RNA and protein levels of UGT1A1 and UGT1A6 in the liver but not the jejunum were increased in male rats fed the HF1 diet. These protein levels did not increase in HF2-fed male rats or HF1-fed female rats. In contrast, the CYP1A2 protein level was decreased in the HF1 but not HF2 diet group, whereas CYP2E1 and CYP4A protein levels were elevated in the HF2 but not HF1 diet group. No significant difference in the organic anion transporter polypeptide (Oatp) 1, Oatp2, multidrug resistance-associated protein (Mrp) 2, or Mrp3 protein levels was found between the standard and HF1 diet groups of male rats. Consumption of the HF1 diet affected the in vivo metabolism of acetaminophen (APAP) such that the area under the APAP-glucuronide plasma concentration-time curve was elevated 2.1-fold in male rats but not female rats. In liver cell nuclei of male rats but not female rats, constitutive androstane receptor (CAR) and proliferator-activated receptor alpha (PPARalpha) protein levels were significantly enhanced by intake of the HF1 diet. Additionally, administration of the PPARalpha agonist clofibrate to male rats up-regulated UGT1A1 and UGT1A6 and down-regulated CYP1A2 in the liver. Taken together, these results indicate that nutritional status may gender-specifically influence the expression and activation of CAR and PPARalpha in liver cell nuclei, and this effect appears to be associated with alterations in UGT1A1 and UGT1A6 expression.

Ontogenic development-associated changes in the expression of genes involved in rat bile acid homeostasis

Ontogenic changes in the rat bile acid (BA) pool, measured enzymatically and by GC-MS, and expression of enzymes (5alpha-reductase, 5beta-reductase, and cytochrome P450 enzymes Cyp7a1, Cyp8b1, Cyp27 and Cyp3a11), transporters [bile salt export pump, sodium taurocholate-cotransporting polypeptide, apical sodium-dependent bile acid transporter, and organic solute transporter alpha/beta (Ostalpha/Ostbeta)], and nuclear receptors [fetoprotein transcription factor (Ftf), farnesoid X receptor (Fxr), small heterodimer partner (Shp), and hepatic nuclear factor 4alpha (HNF-4alpha)], determined by quantitative PCR, were investigated. The absolute size of the BA pool increased progressively up to adulthood, whereas the complexity of its composition was high in fetuses, decreased after birth, increased again progressively up to adulthood, and decreased in aged animals. Allo-cholic acid only appeared early in development, in spite of low 5alpha-reductase expression. The relative size of the BA pool, corrected by liver weight, was maintained from 1 week after birth, except at weaning, when a transient peak accompanied by Shp downregulation and Cyp7a1 upregulation was observed. An imposed weaning delay of 1 week had no effect on the time course of the BA pool size but decreased the proportion of chenodeoxycholic and alpha-muricholic acids, whereas the proportion of cholic acid was increased, probably as a result of Cyp8b1 upregulation. In conclusion, changes in the expression of genes involved in BA homeostasis may play a role in physiological adaptations to digestive functions during the rat life span.

Incorporation of Arachidonic and Stearic Acids Bound to L‐FABP into Nuclear and Endonuclear Lipids from Rat Liver Cells

The incorporation of exogenous fatty acids bound to L-FABP into nuclei was studied. Rat liver cell nuclei and nuclear matrices (membrane depleted nuclei) were incubated in vitro with [1-(14)C]18:0 and 20:4n-6 either free or bound to L-FABP, ATP and CoA. FA esterification in whole nuclei and endonuclear lipids was ATP-CoA-dependent, and with specificity regarding fatty acid type and lipid class. 18:0 and 20:4n-6, free or L-FABP bound, showed the same incorporation and esterification pattern in lipids of whole nuclei. Only 20:4n-6 L-FABP bound was less incorporated into TAG with respect to free 20:4n-6. In the nuclear matrix, 18:0 free or L-FABP bound was esterified with a higher specific activity (SA) into: PtdEtn > PtdIns, PtdSer > PtdCho. 20:4n-6 free or L-FABP bound was esterified into: PtdIns > PtdEtn > PtdCho. 20:4n-6:L-FABP was esterified in endonuclear total-PL and PtdIns with a greater SA with respect to free 20:4n-6 and with a minor one as FFA. To summarize, trafficking of FA to nuclei includes esterification of 18:0 and 20:4n-6 either free or L-FABP-bound, into nuclear and endonuclear lipids by an ATP-CoA-dependent pathway. Endonuclear fatty acid esterification was more active than that in whole nuclei, and independent of the nuclear membrane. Esterification patterns of fatty acids L-FABP-bound or free into whole nuclear lipids were the same whereas in the nuclear matrix, L-FABP could play an important role in the mobilization of 20:4n-6 into specific sites of utilization such as the PtdIns pools.

Identification of NF1 as a silencer protein of the human adenine nucleotide translocase-2 gene.

The human adenine nucleotide translocase-2 (ANT2) promoter contains a silencer region that confers partial repression on the heterologous herpes simplex virus thymidine kinase (HSVtk) promoter [Barath, P., Albert-Fournier, B., Luciakova, K., Nelson, B.D. (1999) J. Biol. Chem.274, 3378-3384]. Two sequences in the silencer (Site-2 and Site-3) are protected in the DNase I assay in vitro, and one of these is a repeated GTCCTG element previously shown to act as the active repressor element. We have now purified the DNA binding protein, and identified it using MALDI-TOF MS as a 33-kDa member of the nuclear factor 1 (NF1) family of transcription factors. NF1 purified from rat liver and HeLa cell nuclei bind to both silencer Site-2 and Site-3, resulting in a DNase I footprint identical to that obtained with purified recombinant NF1. Furthermore, transient transfection experiments with reporter constructs containing mutated silencer Site-2 and/or Site-3 show that both sites contribute to repression of the HSVtk promoter. Finally, chromatin immunoprecipitation analysis reveals that NF1 is bound to both elements on the endogenous HeLa cell ANT2 promoter. Our data support the belief that NF1 acts as a repressor when bound to silencing Site-2 and Site-3 of the ANT2 gene.

Phosphatidyl choline fatty acid remodeling in the hepatic cell nuclei

This study was performed to determine whether fatty acids incorporated into liver cell nuclei phosphatidylcholine (PtdCho) could be remodeled in the isolated nuclear. For this reason, rat liver cell nuclei were incubated in vitro with [1- 14C]20:4n-6-CoA. PtdCho molecular species with the highest specific activity had an unsaturated fatty acid at sn-1 and sn-2 positions (20:4-20:4>>18:2-20:4>18:1-20:4). 16:0-20:4 and 18:0-20:4 PtdChos showed a minor specific activity. When labeled nuclei were reincubated in the absence of labeled substrate with the addition of cytosol, ATP and CoA, the specific activity of 20:4-20:4, 18:2-20:4 and 18:1-20:4 species decreased, while that of 16:0-20:4 and 18:0-20:4 increased. In conclusion, the asymmetric fatty acid distribution of saturated fatty acids at sn-1 position, and unsaturated fatty acids at sn-2 position of nuclear PtdCho molecular species was re-established by an acyl-CoA-dependent remodeling process.

Nuclear localization of phosphatidylinositol 4-kinase beta.

Whereas most phosphatidylinositol 4-kinase (PtdIns 4-kinase) activity is localized in the cytoplasm, PtdIns 4-kinase activity has also been detected in membrane-depleted nuclei of rat liver and mouse NIH 3T3 cells. Here we have characterized the PtdIns 4-kinase that is present in nuclei from NIH 3T3 cells. Both type II and type III PtdIns 4-kinase activity were observed in the detergent-insoluble fraction of NIH 3T3 cells. Dissection of this fraction into cytoplasmic actin filaments and nuclear lamina-pore complexes revealed that the actin filament fraction contains solely type II PtdIns 4-kinase, whereas lamina-pore complexes contain type III PtdIns 4-kinase activity. Using specific antibodies, the nuclear PtdIns 4-kinase was identified as PtdIns 4-kinase beta. Inhibition of nuclear export by leptomycin B resulted in an accumulation of PtdIns 4-kinase beta in the nucleus. These data demonstrate that PtdIns 4-kinase beta is present in the nuclei of NIH 3T3 fibroblasts, suggesting a specific function for this kinase in nuclear processes.

Changes in the pattern of bile acids in the nuclei of rat liver cells during hepatocarcinogenesis

Changes in the pattern of bile acids in the nuclei of rat liver cells during hepatocarcinogenesis

Changes in the pattern of bile acids in the nuclei of rat liver cells during hepatocarcinogenesis

Bile acids reach the nuclei of hepatocytes, where they may play an important role in controlling gene expression by binding to nuclear receptors. In previous studies, changes in the amounts of the different molecular species of bile acids in the hepatocyte nucleus during rat liver regeneration have been reported. The aim of the present work was to investigate whether this also occurs during rat hepatocarcinogenesis. Liver cell nuclei were isolated after homogenization of livers from healthy adult rats (controls) and from rats at different time points during chemically induced hepatocarcinogenesis, corresponding to the stages of foci (12 weeks), hepatoma (20 weeks) and carcinoma (32 weeks). Bile samples from the cannulated common bile duct were collected for 1h from different sets of animals undergoing hepatocarcinogenesis. Bile acids in bile, liver homogenates and isolated nuclei were measured by GC-MS. Because the yield of nuclei isolated changed during the course of hepatocarcinogenesis (control, 20.1%; 12 weeks, 23.6%; 20 weeks, 7.8%; 32 weeks, 5.1%), amounts of bile acids in nuclei were corrected for the amount of DNA in each preparation. During hepatocarcinogenesis, bile acid concentrations in liver homogenates were reduced to approximately half the values obtained in control livers, while the levels of bile acids in both isolated nuclei and bile were not decreased. Hepatocarcinogenesis induced changes in the composition of bile acid pools. These were manifest as an increase in the proportion of cholic acid and a decrease in that of ursodeoxycholic acid in both bile and liver. These modifications differed from the changes seen in the nuclear bile acid pool, where a decrease in the proportion of cholic acid together with an increase in that of ursodeoxycholic acid were the major changes observed during hepatocarcinogenesis. With regard to the 'flat' bile acids (allo-cholic acid plus Delta(5)- or Delta(4)-unsaturated bile acids), a marked hepatocarcinogenesis-induced increase in the output of these species in bile was found. However, these bile acids were only found in liver homogenates at the hepatoma stage, whereas they were not detected in isolated nuclei at any stage of hepatocarcinogenesis. In summary, these results support the existence of a bile acid pool in hepatocyte nuclei whose composition differs from that of the extranuclear bile acid pool. Moreover, they indicate that, during hepatocarcinogenesis, the composition of the nuclear pool undergoes important alterations.

Influence of aging on the carcinogen-induced protein kinase activity in rat liver cell nuclei.

A carcinogen-induced increase in a protein kinase activity was found in cell nuclei of rat liver. The enzyme was extracted from isolated nuclei with a hypotonic buffer, retained to an anion-exchange column, eluted with 0.15 M NaCl containing solution and to be measured for the activity with casein as the substrate, showing a nature of a casein kinase. The change in the activity during the course of aging was studied with 5-, 10-, and 50-week old Wistar male rats. The activity was highest in 5-week-old rat but decreased in 10- and 50-week-old animal. A hepatocarcinogen, thioacetamide, induced an increase in activity in 10-week old rats but rather decreased in 5- and 50-week-old rats. Aging suppresses the activity of this unique enzyme. Thioacetamide abolishes this suppression resulting in an increase in the activity of the enzyme at a certain stage of aging.

Proteins recognized by antibodies against isolated cytological heterochromatin from rat liver cells change their localization between cell species and between stages of mitosis (interphase vs metaphase)

Heterochromatin in the cell nucleus seems to concentrate various proteins, such as Drosophila heterochromatin protein 1, which maintain the repressed state of gene expression. However, it still remains obscure how protein composition related to chromatin structure is different between heterochromatin and euchromatin in interphase nuclei. We isolated cytological heterochromatin from sonicated interphase nuclei obtained from rat liver cells and prepared antisera against it. The dense heterochromatic bodies seen in the preparation of intact nuclei were duplicated in a relatively pure form during the preparation of heterochromatin. In the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, differences between the fractions of heterochromatin and euchromatin were noted by their protein composition. Isolated heterochromatin was then digested by DNase after partial digestion with trypsin and its dense structure changed to become highly sensitive to DNase. The prepared antibodies reacted with the heterochromatin region of rat liver cell nuclei and isolated cytological heterochromatin; however, they did not react with euchromatin. Using immunohistochemistry, the antibodies bound to each cell nucleus in all tissues observed; some cell types were distinguished by their differential stainability (e.g. staining in the cytoplasm). Staining of the mitotic cells showed that the proteins recognized by the antibodies were localized in the cytoplasm and, in part, on the chromosomes. Based on the results of molecular cloning from rat liver cDNA library using the antibodies as a probe, it seemed that the antibodies mainly recognized two proteins similar to arginase and general vesicular transport factor p115, respectively. The results obtained from these experiments reveal that some proteins located in the heterochromatin of interphase liver cell nuclei seem to play important roles in condensing a portion of the chromatin structure during interphase and suggest that proteins composing heterochromatin might be changed according to cell types or the stage of the cell cycle.

CREB controls LAP/C/EBP beta transcription.

LAP/C/EBP beta is a member of the C/EBP family of transcription factors and is involved in hepatocyte-specific gene expression. Recently we showed that, besides its posttranscriptional regulation, LAP/C/EBP beta mRNA is modulated during liver regeneration. Therefore, in this study we investigated mechanisms which control LAP/C/EBP beta gene transcription. Deletion analysis of the 5'-flanking region, located upstream of the start site of transcription in the LAP/C/EBP beta gene, demonstrated that a small region in close proximity to the TATA box is important in maintaining a high level of transcription of the luciferase reporter gene constructs. In gel shift experiments two sites were identified which are important for specific complex formation within this region. Further analysis by cross-linking, super shift, and competition experiments was performed with liver cell nuclear extracts, hepatoma cell nuclear extracts, or recombinant CREB protein. These experiments conclusively demonstrated that CREB binds to both sites in the LAP/C/EBP beta promoter with an affinity similar to that with the CREB consensus sequence. Transfection experiments with promoter constructs where the CREB sites were mutated showed that these sites are important to maintain both basal promoter activity and LAP/C/EBP beta inducibility through CREB. Northern blot analysis and runoff transcription assays demonstrated that the protein kinase A pathway not only stimulated the activity of the luciferase reporter construct but also the transcription of the endogenous LAP/C/EBP beta gene in different cell types. Western blot analysis of rat liver cell nuclear extracts and runoff transcription assays of rat liver cell nuclei after two-thirds hepatectomy showed a functional link between the induction of CREB phosphorylation and LAP/C/EBP beta mRNA transcription during liver regeneration. These results demonstrate that the two CREB sites are important to control LAP/C/EBP beta transcription in vivo. As several pathways control CREB phosphorylation, our results provide evidence for the transcriptional regulation of LAP/C/EBP beta via CREB under different physiological conditions.

Intranuclear distribution of 2,2′,4,4′,5,5′-hexachlorobiphenyl and 2,3,7,8,-tetrachlorodibenzo- p-dioxin

The in vitro intranuclear distribution of the chlorinated aromatic hydrocarbon compounds 2,2′,4,4′,5,5′-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo- p-dioxin was determined in isolated rat liver cell nuclei. Suspended nuclei were incubated with the 3H-labeled congeners, and the incubation terminated by brief UV irradiation. High-intensity UV irradiation at 254 nm changes the reversible association between macromolecules and ligands into covalent linkages and thus stabilizes the equilibrium distribution. The nuclei were then fractionated with the radioactive congeners covalently linked to the purified fractions. The intranuclear distribution of the model compounds was not uniform. The majority of either chemical was attached to the nuclear envelope and to the chromatin fraction. Much lower amounts were bound to nucleoli. The nuclear matrix was almost devoid of the chemicals. Minute amounts of either compound were detected in association with DNA, none with nuclear RNA. The substantial association of these chlorinated hydrocarbon model compounds with chromatin may bear more general biological relevance and point to detrimental effects on the genetic apparatus. The presented method yields an unequivocal profile of the genuine nuclear distribution of photoactivatable chemicals.

Long-chain fatty Acyl-CoA synthetase enzymatic activity in rat liver cell nuclei.

A long-chain fatty acyl-CoA synthetase that catalyzes the activation of long-chain fatty acids as thioesters of CoA, was described in rat liver nuclei. This is the first step for further metabolization of fatty acids in the cell. Up to now, it has been shown that long-chain fatty acyl-CoA synthetase is located in the endoplasmic reticulum, in plasma membrane, in mitochondria and in peroxisomes. The nuclear long-chain fatty acyl-CoA synthetase was assayed using palmitic (16:0), linoleic (18:2n-6) and 8,11,14-eicosatrienoic (20:3n-6) acids as substrates and was stimulated linearly with nuclear protein concentration and with incubation time The higher enzymatic activity was observed with 18:2n-6 and 20:3n-6 acids as substrates. The synthesis of palmitoyl-CoA, linoleyl-CoA and 8,11,14-eicosatrienoyl-CoA followed normal Michaelis-Menten kinetics with respect to the corresponding substrate concentrations. The acyl-CoA synthetase seems to be saturated at a substrate concentration of 12.8 microM for all the acids tested. The apparent Km values decreased in the following order 20:3n-6 > 18:2n-6 > 16:0. The lowest apparent Km for palmitic acid indicates a preference for acylation of this acid in the cell nucleus.

Immunocytochemical localization of melatonin in the harderian gland of Syrian hamster.

The Harderian gland (HG) is a tubulo-alveolar gland found within the ocular orbit of animals which present a nictitating membrane. The Harderian gland is regarded as an extrapineal melatonin producing organ and both, photoperiod and melatonin have been shown to exert an important role in the metabolism and morphological features of such a gland. Our results seem to support the presence of melatonin in the nuclei of the HG cells, although our studies have not definitively proved such presence. An Immunocytochemical anti-melatonin technique was done over free sections of Bouin fixed material obtained from Syrian hamsters. Some of the sections were embedded in an epoxy resin and studied under electron microscope. The presence of positive immunoreaction was observed at the level of the nuclear membranes and in close relation to chromatin. No differences were observed between males and females nor between pinealectomized animals and control ones. Our results suggest the binding of melatonin to the cell nucleus in all cell types of the gland. These observations are in accord with the binding studies performed by Acuña-Castroviejo in purified cell nuclei of rat liver (Acuña-Castroviejo et al., 1994. J. Pineal Res., 16:100-112) and the earlier one by Menéndez-Peláez et al. (1993a,b, J. Pineal Res., 15:59-69; J. Cell Biochem., 53:373-3*2) using the light microscope. Our results seem to support the idea of a nuclear action of melatonin and they agree with the observations of Carlberg and Wiesenberg (1995, J. Pineal Res., 18:171-178) about the activation of some orphan receptors by melatonin.

A high-affinity peripheral benzodiazepine receptor is expressed on nuclei of rat liver cells and a macrophage cell lines: [formula omitted]. Dept. of Pathology and Medicine, The George Washington University School of Medicine, Washington, D.C.

A high-affinity peripheral benzodiazepine receptor is expressed on nuclei of rat liver cells and a macrophage cell lines: [formula omitted]. Dept. of Pathology and Medicine, The George Washington University School of Medicine, Washington, D.C.