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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Ammonia and urea transport across the colonic mucosa was studied by a perfusion technique in four subjects with colonic exclusion for chronic hepatic encephalopathy. 2. Reduction of luminal pH inhibited net and unidirectional transport of ammonia from lumen to plasma, but net absorption from high luminal concentrations persisted at low pH. 3. Neither addition of urea to the perfusate nor intravenous infusion of urea produced a consistent increase in the colonic excretion of ammonia when ammonia-free solutions were perfused. 4. In one subject intravenous infusion of (15N)-ammonium chloride produced rapid labelling of colonic effluent ammonia and within 60 min the specific enrichments of ammonia in effluent and in arterial plasma were approximately equal. 5. During perfusion of nitrogen-free solutions, only small amounts of urea appeared in the effluent, suggesing limited permeability of the colonic mucosa to urea. 6. These results are discussed in relation to the equilibration of ammonia across the colonic mucosa by both ionic and non-ionic diffusion. The lack of evidence of 'juxtamucosal' (as opposed to luminal) ureolysis is in contrast to other observations on the intact colon. The possible reasons for and implications of this discrepancy are discussed.
Clin Sci Mol Med 1975 Apr
PMID:Ammonia and urea transport by the excluded human colon. 23 10

Great progress has been made in the last 5 yr in demonstrating the presence of benzodiazepines (BDZs) in mammalian tissues, in beginning studies on the origin of these natural compounds, and in elucidating their possible biological roles. Many unanswered questions remain regarding the sources and biosynthetic pathways responsible for the presence of BDZs in brain and their different physiological and/or biochemical actions. This essay will focus on recent findings supporting that: (1) BDZs are of natural origin; (2) mammalian brain contains BDZs in concentrations ranging between 5 x 10(-10)-10(-8) M; (3) dietary source of BDZs might be a plausible explanation for their occurrence in animal tissues, including man; (4) the formation of BDZ-like molecules in brain is a possibility, experimentally supported; (5) BDZ-like molecules including diazepam and N-desmethyldiazepam are elevated in hepatic encephalopathy; and (6) natural BDZs in the brain are involved in the modulation of memory processes. Future studies using the full range of biochemical, physiological, behavioral, and molecular biological techniques available to the neuroscientist will hopefully continue to yield exciting and new information concerning the biological roles that BDZs might play in the normal and pathological functioning of the brain.
Mol Neurobiol 1992
PMID:Benzodiazepines in the brain. Their origin and possible biological roles. 133 55

The possible involvement of taurine in the pathogenesis of hepatic encephalopathy was studied in rats injected with thioacetamide. Spontaneous release of exogenous labeled taurine was not affected in any brain area studied, but the potassium-stimulated release was enhanced in the striatum in thioacetamide-treated rats. High concentrations of ammonium ions also evoked greater release of taurine from striatal slices in rats with thioacetamide-induced hepatic encephalopathy.
Mol Chem Neuropathol 1991 Feb
PMID:Taurine release from brain slices in thioacetamide-induced hepatic encephalopathy in rats. 191 Mar 55

The effect of hyperammonemia of varying degree and duration on the gamma-glutamyl-transpeptidase (GGT) activity was studied in the homogenates and capillaries of different brain regions of the rat. "Acute" hyperammonemia (750 and 600 mg of ammonium acetate per kg b.w. were injected i.p. at 30 min interval, and the animals were decapitated immediately), in which blood ammonia was increased 14-fold, and brain ammonia six-fold above the control level, produced a 20% increase of the enzyme activity in cerebellum, and a 17% decrease in gyrus dentatus, but had no effect in the frontal cortex and the CA1 and CA3 regions of hippocampus. "Subchronic" hyperammonemia (two injections of 600 mg ammonium acetate/kg were given at 24 h intervals, and tissue samples were removed 24 h later), that was accompanied by only a 60% increase of blood or brain ammonia, increased the activity in cerebellum to 38% above control, but produced no effect in the other brain regions. "Chronic" hyperammonemia (three injections of 600 mg ammonium acetate/kg at 24 h intervals and excision of tissue samples 30 min after the last injection), in which blood and brain ammonia were, respectively, 60 and 100% higher than in control animals, elevated the GGT activity in the cerebellum by 57%, in CA1 by 15%, and in CA3 by 21%, but produced no effect in the frontal cortex or gyrus dentatus. By contrast, "chronic" hyperammonemia produced a 30% increase of GGT activity in cerebral cortical capillaries, but only a 10% increase in hippocampal capillaries, and no change in cerebellar capillaries. The results suggest that, hyperammonemia of relatively long duration may contribute to the enhancement of brain GGT activity observed in chronic forms of hepatic encephalopathy. However, ammonia does not appear to activate the enzyme directly.
Mol Chem Neuropathol
PMID:The effect of acute and repeated hyperammonemia on gamma-glutamyl transpeptidase in homogenates and capillaries of various rat brain regions. 198 79

Most of the brain glycogen, a major energy reserve that can be mobilized in response to increased neuronal activity, resides in the astrocyte, the site of the neuropathological abnormality found in hepatic encephalopathy (HE). Ammonia, a neurotoxin implicated in the pathogenesis of HE, has been reported to cause a depletion of glycogen in primary astrocyte cultures. To further investigate the action of ammonia on glycogen levels, cultured astrocytes were exposed to ammonium chloride (1-5 mM) for various times up to 7 d. Treatment with ammonia for 24 h did not alter deoxyglucose uptake, but significantly lowered peak glycogen values (found at 1.5 h following feeding with medium containing 5.5 mM glucose) in a concentration-dependent manner. This inhibitory effect was not observed after longer exposure times to ammonia. Three day treatment of cells did, however, significantly reduce norepinephrine-stimulated glycogenolysis, an effect not seen after 1 d of ammonia treatment. Part of the neurotoxic action of long term ammonia exposure in humans and experimental animals may be to inhibit the breakdown of glycogen. The effect of ammonia on astrocyte glycogen synthesis and/or breakdown may disrupt glial neuronal signaling and thus play a role in the pathogenesis of HE.
Mol Chem Neuropathol 1993 Aug
PMID:The action of ammonia on astrocyte glycogen and glycogenolysis. 839 86

The activities of the cytoplasmic and plasma membrane marker enzymes: lactate dehydrogenase (LDH) and acetylcholinesterase (AChE), respectively, were measured in the cerebral homogenates, in the synaptic and nonsynaptic mitochondrial fractions, and in the postmitochondrial supernatants derived from rats in which a 3-d, moderately hyperammonemic condition (no more than 120% increases in blood ammonia) was produced by repeated administration of ammonium acetate (simple hyperammonemia, SHA) or a hepatotoxin, thioacetamide (TAA) (hepatic encephalopathy, HE). As measured in the homogenate and postmitochondrial supernatants, neither of the enzyme activities was affected by SHA or HE. SHA and HE increased the synaptic mitochondrial LDH activity by respectively 53 and 24%, but reduced this enzyme activity in nonsynaptic mitochondria by 19%. Both conditions stimulated the synaptic and nonsynaptic mitochondrial AChE activity by 30-40%. By contrast, the only significant change produced in these fractions by in vitro treatment with a toxic (3 mM) concentration of ammonium chloride was a slight decrease of LDH activity in nonsynaptic mitochondria and postmitochondrial supernatants. It is concluded that moderate hyperammonemia modifies subsequent separation of both cerebral classes of mitochondria from the cytosolic and plasma membrane components. This modification is likely to reflect subtle hyperammonemia-related changes in the physicochemical properties of the two mitochondrial classes and/or other subcellular components.
Mol Chem Neuropathol 1993 Apr
PMID:Changes in the cytoplasmic (lactate dehydrogenase) and plasma membrane (acetylcholinesterase) marker enzymes in the synaptic and nonsynaptic mitochondria derived from rats with moderate hyperammonemia. 850 4

Mitochondrial trifunctional protein (TP), an enzyme of beta-oxidation, is a multienzyme complex composed of four molecules of the alpha-subunit (HADHA) containing the enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase domains and four molecules of the beta-subunit (HADHB) containing the 3-ketoacyl-CoA thiolase domain. An inborn error of this enzyme complex can cause sudden infant death syndrome, acute hepatic encephalopathy or liver failure, skeletal myopathy, or hypertrophic cardiomyopathy. TP deficiency is classified into two different biochemical phenotypes: one represents the existence of both subunits and the lack of only the 3-hydroxyacyl-CoA dehydrogenase activity and the other represents the absence of both subunits and the lack of all three TP activities, although their clinical features are similar. We have identified two Japanese patients with this disorder. Three enzyme activities of TP were undetectable in fibroblasts from these two patients. We detected two mutations in the HADHB gene from two Japanese patients, an exonic single T insertion which created a new cryptic 5' splice site and a G1331A transition (R411 K). Patient 1 was a compound heterozygote, while patient 2 was a homozygote of a G1331A transition.
Hum Mol Genet 1997 Aug
PMID:Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency. 925 66

Alzheimer type II astrocytosis is the pathological hallmark of hepatic encephalopathy. These astrocytes undergo a characteristic morphological change and, in addition, lose immunoreactivity for glial fibrillary acidic protein (GFAP). However, a previous study in the portacaval shunted rat, a model of hepatic encephalopathy, revealed increased rather than decreased GFAP immunoreactivity in Bergmann glia, a specialized group of cerebellar astrocytes. In the present study, sections of cerebellar vermis from 15 cirrhotic patients with hepatic encephalopathy and varying degrees of Alzheimer type II astrocytosis were stained using antisera to GFAP. The Bergmann glial cells did not show altered GFAP immunoreactivity compared to controls. In addition, the degree of GFAP immunoreactivity was not correlated with the degree of Alzheimer type II change nor related to the aetiology of the liver disease. These results suggest a differential response of Bergmann glia in human hepatic encephalopathy.
Mol Chem Neuropathol 1997 Aug
PMID:Distinctive pattern of Bergmann glial pathology in human hepatic encephalopathy. 933 69

Biotinyl derivatives of several lectins were used to study the localization of glycoconjugates in the cerebral microcapillaries and various brains of rats given at 24-h intervals two i.p. administrations of a hepatotoxin-thioacetamide (TAA) and examined 21 d posttreatment. At this time, the rats were asymptomatic with regard to hepatic encephalopathy but showed specific and selective changes in the blood-brain-barrier (BBB) transport of basic amino acid, but no BBB damage, and region-specific neuronal injury in the hippocampus and neocortex. The lectins tested recognized the following sugar residues: beta-D-galactosyl (Ricinus communis agglutinin [RCA-1]); N-acetyl-glucosaminyl and N-acetyl-neuraminic acid (wheat-germ agglutinin [WGA]); N-acetyl-D-galactosaminyl (Helix pomatia agglutinin [HPA]); beta-D-galactosyl and D-galactosyl neuraminic acid (peanut agglutinin [PNA]), and alpha-D-galactosyl and alpha-D-mannosyl (concanavalin A [Con A]). The treatment markedly decreased the binding to the cerebromicrovascular network of the hippocampus and neocortex of RCA-1 and WGA. The binding of these two lectins to their complementary monosaccharide residues appears to reflect subtle changes in BBB function, with a detection threshold below the conventional BBB permeability tests. The changes in the binding of the other two lectins: an increase of HPA binding and a decrease of Con A binding, confined to neocortical neurons and pyramidal cells of hippocampus injured by TAA treatment.
Mol Chem Neuropathol
PMID:Lectin histochemistry of the rat brain following thioacetamide-induced hepatic failure. 943 65

Hepatic encephalopathy (HE) is characterized by symptoms pointing at disturbances in glutamatergic neurotransmission in the brain, particularly in the striatum. The binding parameters of ligands specific for different recognition sites in the N-methyl-D-aspartate (NMDA) receptor complex and the distribution of the receptor subunit mRNAs (NR1, NR2A-D) were assessed in rats with acute HE induced with a hepatotoxin, thioacetamide (TAA). The binding of: 1. L-[3H]glutamate (NMDA-displaceable); 2. [3H]dizocilpine and N-(1-[2-thienyl]-cyclohexyl) [3H]piperidine ([3H]TCP); and 3. The coactivator site agonist [3H]glycine was assayed in purified membranes of the cerebral cortex, hippocampus, and striatum. In HE rats, Bmax of NMDA-displaceable glutamate binding was increased in the cerebral cortex and hippocampus, but slightly decreased in the striatum. In this region, the binding affinity was also slightly increased. In HE, Bmax of [3H]dizocilpine binding was unchanged in the striatum and cerebral cortex, but substantially decreased in the hippocampus. Pretreatment with phorbol ester enhanced the binding of dizocilpine more in HE than in control rats. Bmax of [3H]TCP binding was decreased in the cerebral cortex and striatum, but increased in the hippocampus. The different responses of these two phencyclidine site antagonists to HE may be indicative of a conformational change within the ion channel and/or the presence of microdomains reacting differently to extrinsic factors. HE did not affect glycine binding, but potentiated the maximal stimulation of [3H]dizocilpine binding by glycine in the cerebral cortex. The results emphasize the brain region and domain specificity of the responses of the NMDA receptor complex to HE.
Mol Chem Neuropathol
PMID:Effects of thioacetamide-induced hepatic failure on the N-methyl-D-aspartate receptor complex in the rat cerebral cortex, striatum, and hippocampus. Binding of different ligands and expression of receptor subunit mRNAs. 943 66


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