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At least 793 records · Page 44Linked to original sources
PubMed1994

Block of GABA-transaminase modifies GABAergic transmission at the crayfish synapses.

1. The cytosolic concentration of a neurotransmitter is believed to be an important factor determining its release. The effects of ethanolamine-O-sulfate (EOS), a gamma-aminobutyric acid (GABA)-transaminase blocker, on GABAergic postsynaptic and presynaptic inhibitory neurotransmission were examined in the crayfish opener neuromuscular synapses. 2. Intracellular recordings of evoked excitatory (EPSPs) and inhibitory postsynaptic potentials (IPSPs) as well as loose macropatch clamp measurements of excitatory (EPSCs) and inhibitory postsynaptic currents (IPSCs) were used to evaluate the effects of the drug, which was applied exclusively to the nerve bundle. 3. Under normal conditions, a stimulus train to the inhibitor before the excitor stimulation elicited two phases of inhibition: 1) a large reduction in EPSP amplitude associated with a decrease in its time constant of decay (tau D) at time intervals of 0-15 ms and 2) a moderate decrease in EPSP amplitude with a small change in EPSP tau D at intervals of 15-90 ms. EOS treatment selectively increased the inhibition of phase 2. 4. The muscle membrane electrical parameters and the existing postsynaptic tonic release of GABA were not affected by the drug. 5. EOS did not alter the IPSP's parameters such as amplitude, reversal potential, and conductance. 6. Quantal analysis of single IPSCs revealed no significant changes in the statistical parameters such as quantum size (q), quantal content (m), number of active zones (n), or probability of release (p). 7. Quantal analysis of EPSCs, released after interaction with the inhibitor, did exhibit a large reduction in m without any effect on q. 8. These results demonstrate that EOS has a specific and differential effect on neural transmission in two synapses of the same axon: it increases presynaptic inhibition without significant effect on the postsynaptic inhibitory mechanism.

4-Aminobutyrate Transaminase↗
PubMed1989

Potential antidepressant properties of subchronic GABA transaminase inhibitors in the forced swimming test in mice.

We carried out the forced swimming test in mice to investigate the antidepressant potentials of GABA transaminase (GABA-T) inhibitors including aminooxyacetic acid, ethanolamine-O-sulfate, gamma-vinyl GABA (GVG) and valproic acid (VPA). In acute experiments only GVG reduced immobility. Following chronic oral administration via drinking water containing the drugs, immobility was significantly reduced at days 5 and 10 in all of the GABA-T inhibitors examined. The tolerance of the anti-immobility effect, however, occurred at day 20. Brain GABA contents showed moderate to marked increase during the session with the exception of VPA, which did not alter GABA contents. These results suggest that subchronic GABA-T inhibitors possess antidepressant properties, though the anti-immobility effect of GABA-T inhibitors did not directly correlate with the increase in brain GABA.

4-Aminobutyrate Transaminase↗
PubMed1983

Human red cell glutamic-pyruvic transaminase polymorphism in Serbia, Yugoslavia.

The polymorphism of red cell glutamic-pyruvic transaminase (GPT) was studied in 277 unrelated voluntary blood donors from the population of Serbia (Yugoslavia). The following phenotype frequencies were observed: GPT 1 0.309, GPT 2-1 0.454 and GPT 2 0.206, while gene frequencies were: GPT1 0.556 and GPT2 0.454.

Alanine Transaminase↗
PubMed1984

Genetic polymorphism of glutamate-pyruvate transaminase and glyoxalase I in Colombia.

Genetic polymorphism of red cell enzymes glutamate-pyruvate transaminase (GPT) and glyoxalase I (GLO) was investigated in five villages of the Colombian Andes. The GPT1 and GLO1 gene frequencies show a considerable range, but compatible to the range of European populations. In both the systems there is slight excess of observed homozygosity suggesting that the infrastructure of the subpopulations may be influenced by inbreeding.

Alanine Transaminase↗
PubMed1987

Genetic polymorphism of red cell glutamate-pyruvate transaminase in Japanese.

Six hundred and eight red cell hemolysates were screened for glutamate-pyruvate transaminase (GPT) by means of isoelectric focusing. Two new variant phenotypes were detected, neither of which could be distinguished from GPT2-1 and GPT2 by conventional starch gel electrophoresis. The two types were considered to correspond to GPT2B-1 and GPT2A-2C reported previously in samples of European origin.

Alanine Transaminase↗
PubMed1989

Glutamate-pyruvate transaminase subtypes in Singapore ethnic groups.

Autopsy liver samples from 244 Chinese, 119 Malays and 136 Indians were screened for glutamate-pyruvate transaminase (GPT) subtypes by starch-gel electrophoresis and isoelectric focusing at pH 5-7. Altogether, ten phenotypes controlled by four alleles (GPT1, GPT2A, GPT2B and GPT3) were identified. There was no significant difference in the frequency of GPT alleles between the ethnic groups. The distribution of GPT types was in agreement with the Hardy-Weinberg equilibrium in all the ethnic groups.

Alanine Transaminase↗
PubMed1995

Impact of decreased serum transaminase levels on the evaluation of viral hepatitis in hemodialysis patients.

The value of serum transaminases (ST) in evaluating hepatitis B (HBV) and C (HCV) infection was studied in 217 hemodialysis (HD) patients and 804 normal controls. Mean serum aspartate aminotransferase (AST) was 22.3 (22.0-22.7) and 22.6 (21.6-23.6) IU/l or 0.371 (0.366-0.378) and 0.376 (0.36-0.393) mu kat/l in controls and HD patients, respectively (nonsignificant), while mean serum alanine aminotransferase (ALT) was 20.3 (19.9-20.7) and 16.3 (15.3-17.3) IU/l or 0.338 (0.331-0.345) and 0.271 (0.255-0.288) mu kat/l in these two groups (p < 0.001). However, both AST and ALT became significantly depressed in HD patients after adjusting for age, gender, HBV surface antigen (HBsAg) and anti-HCV. The usual practice of regarding AST and ALT as being 'abnormal' in evaluating viral hepatitis when they exceeded the upper reference range (40 and 46 IU/l or 0.666 and 0.766 mu kat/l in our laboratory) was then critically assessed by the receiver operating characteristic (ROC) curve. ROC analysis showed that ST was useless in detecting HBsAg, while the best cutoff point for detecting the presence of anti-HCV was 18 IU/l (0.3 mu kat/l) for AST and 16 IU/l (0.266 mu kat/l) for ALT in HD patients, respectively. These are considerably lower than the conventional criteria for an 'abnormal' ST. We conclude that ST are decreased in HD patients and that the cutoff value of ST for detecting HCV should be set at lower levels to enhance their diagnostic yield.

Alanine Transaminase↗
PubMed1976

Expression of hormonally induced tyrosine transaminase in normal, host liver and three Morris hepatomas.

Cytoplasmic tyrosine transaminase (L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was partially purified from normal, host liver and three Morris hepatomas and subsequently resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically in situ on the gels. Seven enzymatically active forms were detected in normal liver. The presence of growing hepatomas altered significantly the expression of this enzyme. Only one, two and four activity peaks were detected in the host liver of animals with highly (most liver-like), well and poorly (least liver-like) differentiated hepatomas, respectively. Similarly, only one, four and six peaks were detected, respectively, in highly, well and poor differentiated hepatomas.

Animals↗
PubMed1987

Effect of maternal fasting on ovine fetal and maternal branched-chain amino acid transaminase activities.

Activities of branched-chain amino acid transaminase were assayed in maternal skeletal muscle, liver and fetal skeletal muscle, cardiac muscle, liver, kidney and placenta obtained from fed and 5-day-fasted late gestation ewes. Very high activities were found in placenta; fetal skeletal muscle also had high activity. Fetal brain had intermediate activity, followed by cardiac muscle and kidney. Fetal liver possessed negligible activity. Activities were low in both maternal liver and skeletal muscle. Trends were seen for fasting to increase activities in fetal placenta, skeletal muscle, brain, kidney, heart and maternal liver, but these changes were statistically significant only for fetal brain and placental tissue. Fetal skeletal muscle activity was 100 times that of maternal skeletal muscle. These data imply differences in the metabolism of the branched-chain amino acids by fetal and adult ruminants and expand the thesis that branched-chain amino acids are important to the metabolism of the ovine fetus.

Amino Acids, Branched-Chain↗
PubMedDate not supplied

Sequential neuropathology of dogs treated with vigabatrin, a GABA-transaminase inhibitor.

Vigabatrin (Sabril) is a gamma-aminobutyric acid-transaminase (GABA-T) inhibitor that is effective in the treatment of certain types of drug-resistant or uncontrolled epilepsy but is known to cause microscopic vacuolation (intramyelinic edema) in the brains of treated rats, mice, and dogs. The effects of high oral doses (300 mg/kg/day) of vigabatrin administered orally to Beagle dogs were studied during treatment weeks 1-12 and recovery weeks 13, 14, 16, 20, 24, and 28. Emesis, loose stools, and anorexia and 3 drug-related deaths were observed during the first 4 wk of treatment but were virtually nonexistent thereafter because of adaptation to the drug aided by food supplementation. In more sensitive areas of the brain (columns of the fornix, thalamus, and hypothalamus), microscopic quantitative differences between background vacuolation in controls and drug-related vacuolation in treated dogs could be delineated after 4 wk, generally reached highest levels of severity between 8 and 12 wk, and were reversible upon cessation of dosing. Inhibition of brain GABA-T and elevation of brain GABA were noted after 1 wk of treatment. During the course of treatment vigabatrin ranged between 4-17 nmol/ml (plasma) and 42-1,570 nmol/ml [cerebrospinal fluid (CSF)] while CSF GABA concentrations were 4-32 nmol/ml (treated dogs) and 0.1-0.6 nmol/ml (control dogs). Although the cause of vigabatrin-induced microvacuolation is unknown, the results of the study demonstrated that GABA-T inhibition with subsequent GABA elevation occurred within the first week of treatment and was followed by the onset of detectable microvacuolation several weeks later.

4-Aminobutyrate Transaminase↗
PubMed1994

Inhibition of GABA transaminase enhances light-induced circadian phase delays but not advances.

The CNS neurotransmitter GABA is distributed extensively throughout the suprachiasmatic nucleus, the site of circadian pacemaker cells in mammals. Pharmacological agents that act at GABAA receptors alter specific circadian responses to light and may induce phase shifts of circadian rhythms. In the present study, the role of endogenously released GABA in rhythm regulation was investigated using vigabatrin (gamma-vinyl GABA), an agent that has been shown to increase chronically or acutely the CNS levels of this neurotransmitter by inhibiting GABA transaminase. In Experiment 1, hamsters in constant darkness (DD) received a saline or a vigabatrin injection 1 hr before a 15-min, 700-lux light pulse. Vigabatrin increased photic phase delays but did not affect advances. In Experiment 2, vigabatrin delivered chronically via osmotic minipump treatment did not affect locomotor activity period in DD. However, after 14 days of infusion, photic phase delays (but not advances) were greatly increased in the vigabatrin group. In Experiment 3, in constant light (LL), chronic vigabatrin-treated animals showed an increased period that returned to pretreatment values after the 14-day drug infusion. The results are consistent with the phase-dependent effects of other agents that alter GABA neurotransmission. The data support the general hypothesis that GABA modulates the circadian responses to light in a phase-dependent manner, and may participate in entrainment to light-dark cycles by influencing the relative responsiveness to light in the early and late subjective night.

4-Aminobutyrate Transaminase↗
PubMed1981

Elevations in serum transaminases and alkaline phosphatase secondary to papaverine hydrochloride.

A case of papaverine-induced elevated liver function tests occurred in a 58-year-old female with peripheral vascular disease after she received papaverine hydrochloride 150 mg bid over a two- to three-week period. The patient presented with abnormal elevations in serum transaminases (SGOT and SGPT) and alkaline phosphatase. The papaverine was discontinued, and the elevated enzymes returned to normal within three weeks.

Alkaline Phosphatase↗
PubMed1987

Immunoreactive GABA transaminase within the pancreatic islet is localized in mitochondria of the B-cell.

Subcellular localization of gamma aminobutyrate-alpha-ketoglutarate transaminase (GABA-T) in the pancreatic islets of Langerhans was determined by use of an electron microscopic, immunogold post-embedding protocol. The objective of this study was to define the islet cell distribution and subcellular localization of GABA-T. Within the islet, GABA-T was found only in the B-cells and was localized in mitochondria; 78 mitochondria contained 336 gold particles, whereas 245 secretory granules contained only 18 gold particles. Although studies utilizing either the isolated perfused pancreas or cultured islets have shown that exogenous GABA modulates D-cell secretion, in this study immunoreactive GABA-T, the catabolic enzyme for GABA, was not detectable in A- and D-cells of the islet. Control studies substituting normal rabbit serum for the GABA-T antiserum resulted in absence of labeling. These results indicate that the high concentration of GABA present in islet B-cells is catabolized by GABA-T in the mitochondrial compartment, consistent with the possibility that GABA functions as a mediator of B-cell activity.

4-Aminobutyrate Transaminase↗
PubMed2006

A new citryl glycoside from Gastrodia elata and its inhibitory activity on GABA transaminase.

A new citryl glycoside, trimethylcitryl-beta-D-galactopyranoside (1) along with a known phenolic compound, gastrodigenin (2) have been isolated from the active fraction of the rhizomes of Gastrodia elata (Orchidaceae). Their structures were elucidated on the basis of spectroscopic data and chemical reaction. 1 inhibited GABA transaminase activity by 56.8% at the final concentration of 10 microg/ml.

4-Aminobutyrate Transaminase↗
PubMed2004

Resistance imparted by traditional Chinese medicines to the acute change of glutamic pyruvic transaminase, alkaline phosphatase and creatine kinase activities in rat blood caused by noise.

The activities of serum glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP) and creatine kinase (CK) in rats injected or not with the Chinese medicines, Astragali, Rhodiolae and Ligusticum, were determined after noise exposure. Noise at 95 and 105 dB significantly increased the activities of GPT, ALP and CK, and showed a dependence on the exposure time. The injection of each medicine significantly suppressed the increased enzyme activities by 95 and 105 dB noise.

Alanine Transaminase↗
PubMed2005

Patients with chronic hepatitis C and normal transaminases.

Hepatitis C virus infection evolves progressively persisting in the majority of patients (85%). Most patients have high ALT (alanine aminotransferase) levels and approximately 25% normal ALT. The latter are usually female and there is no association between genotype and severity of hepatic lesion. Histologic analysis usually shows small lesion and absence or low amount of fibrosis, despite cirrhosis having been reported. Aiming at assessing prevalence, demographic, genotypical and anatomopathological characteristics in patients with normal ALT levels, we have carried out a study of 68 chronic hepatitis C patients between January 1997 and April 2000. There was a prevalence of 13.8% chronic hepatitis C patients with normal ALT levels, 45.6% of which were male and 54.4% female, the mean age being 38 +/- 13 years. We found a predominance of genotype 1 in 84.7% of the patients, genotype 2 in 6.8% and genotype 3 in 10.7%. In 52.9% of the cases liver biopsies revealed liver reaction, periportal activity score 0-1 was observed in 85.3% of the patients and score 2-4 was seen in 14.7%. Structural activity score 0-1 was seen in 73.5% of the patients and score 2-4 in 26.5% of them. Periportal activity > or = 2 and structural activity > 1 was seen in 29%, but steatosis was not seen in 73.5%. Our results suggest the need to revisit for liver biopsy practice in patients with chronic hepatitis C and normal transaminases.

Adolescent↗
PubMed2003

GABA transporters and GABA-transaminase as drug targets.

The fine-tuning and homeostatic balance of the GABAergic inhibitory tone in the central nervous system (CNS) is a prerequisite for controlling the excitatory neurotransmission. This principal mechanism for controlling excitation is inhibition which has been the topic of intensive research covering all known functional entities of the GABAergic synapse. The therapeutical scope for targeting the GABA system covers a large number of neurological and psychiatric disorders. This review focuses on the major inactivation systems for GABAergic neurotransmission, the GABA transporters (GATs) and the GABA catabolic enzyme GABA -transaminase (GABA-T) as drug targets. Tiagabin and Vigabatrin, two anti-epileptic drugs on the market today, specifically inhibit GABA transport and metabolism, respectively. However, previous and recent evidence has clearly demonstrated the importance and differential functional roles of glial and neuronal GABA uptake and the metabolic fate of the sequestered neurotransmitter GABA in these cells. Moreover, the diverse expression patterns of the GABA transporters, in combination with development of GAT inhibitors with novel pharmacological profiles may initiate a renaissance for these inactivation systems as drugs targets. In particular, further research to elucidate the specialized physiological function of the GATs combined with their differential spatial expression could be of fundamental importance for the understanding of concerted action with regard to the fine-tuning of the GABAergic inhibitory tone. As such, selective targeting and modulation of GABA transporter subtypes and cell-specific GABA uptake and metabolism is of therapeutical interest in GABA-related CNS disorders, including epilepsy.

4-Aminobutyrate Transaminase↗