Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P80404 (GABA transaminase)
 786 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

gamma-Aminobutyric acid (GABA), a prominent inhibitory neurotransmitter, is present in high concentrations in beta-cells of islets of Langerhans. The GABA shunt enzymes, glutamate decarboxylase (GAD) and GABA transaminase (GABA-T), have also been localized in islet beta-cells. With the recent demonstration that the 64,000-M, antigen associated with insulin-dependent diabetes mellitus is GAD, there is increased interest in understanding the role of GABA in islet function. Only a small component of beta-cell GABA is contained in insulin secretory granules, making it unlikely that GABA, coreleased with insulin, is physiologically significant. Our immunohistochemical study of GABA in beta-cells of intact islets indicates that GABA is associated with a vesicular compartment distinctly different from insulin secretory granules. Whether this compartment represents a releasable pool of GABA has yet to be determined. GAD in beta-cells is associated with a vesicular compartment, similar to the GABA vesicles. In addition, GAD is found in a unique extensive tubular cisternal complex (GAD complex). It is likely that the GABA-GAD vesicles are derived from this GAD-containing complex. Physiological studies on the effect of extracellular GABA on islet hormonal secretion have had variable results. Effects of GABA on insulin, glucagon, and somatostatin secretion have been proposed. The most compelling evidence for GABA regulation of islet hormone secretion comes from studies on somatostatin secretion, where it has an inhibitory effect. We present new evidence demonstrating the presence of GABAergic nerve cell bodies at the periphery of islets with numerous GABA-containing processes extending into the islet mantle. This close association between GABAergic neurons and islet alpha- and delta-cells strongly suggests that GABA inhibition of somatostatin and glucagon secretion is mediated by these neurons. Intracellular beta-cell GABAA and its metabolism may have a role in beta-cell function. New evidence indicates that GABA shunt activity is involved in regulation of insulin secretion. In addition, GABA or its metabolites may regulate proinsulin synthesis. These new observations provide insight into the complex nature of GABAergic neurons and beta-cell GABA in regulation of islet function.
 ...
PMID:Structural and functional considerations of GABA in islets of Langerhans. Beta-cells and nerves. 193 99

Low-frequency vibration, irrespective of its duration (20 Hz, A = 0.4 mm), is shown to increase GABA level, glutamatedecarboxylase enzyme activity (EC 4.1.1.15) in the large hemispheres, cerebellum, brain stem of adult male rats (12 months). Meanwhile GABA aminotransferase activity (EC 2.6.1.19) remains, mainly, unchanged. The observed shifts are more clear under 30 min vibration than under 7h and 30 day effects. Glutaminic and aspartic acids content increases under 30 min and decreases under 7h and 30 day vibration in the given brain structures.
 ...
PMID:[The effect of low-frequency vibration on GABA metabolism in brain structures]. 205 25

Freeze-dried sections (14 microns thick) of retinal layers were prepared from mice with retinal degeneration (C3H strain) and control mice (C57BL strain). The weighed sections (2-30 ng dry weight) were analyzed using our microassay methods. In the control retina, gamma-aminobutyric acid (GABA) concentration and glutamate decarboxylase (GAD) activity, on a dry weight basis, increased from birth to 9 weeks of age and decreased slightly at 20 weeks. In the degenerated retina, the levels of GABA and GAD activity were higher at birth than in the control retina, and continued to increase until 20 weeks of age, at which time the GAD activity reached a markedly high level. This increase was found when the total GABA and GAD levels per retina were determined. In the normal retinal layers, GABA and GAD were confined primarily to the inner plexiform layer. In the degenerated retina, GAD activity gradually increased in the inner layers during postnatal development, but by 20 weeks the increase was most prominent in the inner part of inner nuclear layer and in the outer part of inner plexiform layer. GABA transaminase activity and its distribution were not much different in both normal and degenerated retinas during development.
 ...
PMID:gamma-Aminobutyric acid system in developing and degenerating mouse retina. 230 18

(3R,4R),(3S,4S)- and (3R,4S),(3S,4R)-4-amino-5-fluoro-3-phenylpentanoic acid (1a and 1b) were synthesized and studied as selective inactivators of gamma-aminobutyric acid (GABA) aminotransferase. Neither compound caused time-dependent inactivation of the enzyme. Neither compound underwent enzyme-catalyzed transamination nor was fluoride ion eliminated from either compound by the enzyme. No 3-phenyllevulinic acid, the product of elimination of HF followed by enamine hydrolysis, was detected. However, both 1a and 1b were competitive reversible inhibitors of GABA aminotransferase; the Ki for 1a was smaller than the Km for GABA. These results suggest that 1a and 1b bind to the active site of GABA aminotransferase, but gamma-proton removal does not occur. Whereas (S)-4-amino-5-fluoropentanoic acid (AFPA) is a potent inhibitor of L-glutamic acid decarboxylase (GAD), neither 1a nor 1b at concentrations 40 times the Ki of AFPA caused any detectable competitive inhibition of GAD. Therefore, the incorporation of a phenyl substituent at the 3-position of AFPA confirms selective inhibition of GABA aminotransferase over GAD.
 ...
PMID:Selective inhibition of gamma-aminobutyric acid aminotransferase by (3R,4R),(3S,4S)- and (3R,4S),(3S,4R)-4-amino-5-fluoro-3-phenylpentanoic acids. 230 43

C57BL/10Bg sps/sps mice display behavioral arrest, similar to generalized absence seizures. Compared with the parent strain C57BL/10Bg SPS/SPS, the activities of glutamate decarboxylase (GAD, E. C. 2.6.1.15), GABA aminotransferase (GABA-T, E. C. 2.6.1.19), aspartate aminotransferase (ASP-T, E. C. 2.6.1.1), and glutamate dehydrogenase (GDH, E. C. 1.4.1.3) in whole brain crude supernatant were significantly reduced in the sps/sps mice. Alanine aminotransferase activity (ALA-T, E. C. 2.6.1.2), was not altered in any of the strains, and normalization of GAD, GABA-T and GDH activities by that of ALA-T, further revealed significant differences between the normal strain (SPS/SPS), the heterozygotes (SPS/sps), and behavioral arrest (sps/sps) mice. These results suggest the possible involvement of GABAergic and glutamatergic neurotransmission in the absence-like behavior displayed by sps/sps mice. Open field behavior of C57BL/10Bg sps/sps mice is characterized by periods of marked inactivity which easily distinguish affected homozygotes, from their heterozygotes littermates.
 ...
PMID:The C57BL/10Bg sps/sps mouse: a mutant with absence-like seizures; neurochemical and behavioral correlates. 239 34

The concentration of gamma-aminobutyric acid (GABA), the activities of related enzymes, i.e. glutamate decarboxylase and GABA transaminase, as well as the level of specific GABA binding sites were determined in ovaries and fallopian tubes obtained surgically from 31 women. None of the biochemical parameters examined showed a correlation with the age and hormonal background (serum estradiol and progesterone levels) of the patients. The respective ovarian and tubal values did not differ significantly in groups operated on because of uterine myoma and carcinoma. In organs from pregnant women, however, most GABAergic markers altered significantly. These findings indicate some gestation-related role for the ovarian and tubal GABA systems in humans.
 ...
PMID:Gamma-aminobutyric acid, its related enzymes and receptor-binding sites in the human ovary and fallopian tube. 255 96

The immunocytochemical distribution of gamma-aminobutyric acid (GABA), GABA synthesizing enzyme; L-glutamate decarboxylase (GAD) and degradative enzyme; GABA transaminase (GABA-T) in the chicken vestibular endorgans and the vestibular ganglion was investigated. GABA and GAD-like immunoreactivity were confined to the sensory hair cell cytoplasm, suggesting that GAD synthesizes GABA in the hair cell. GABA-T-like immunoreactivity, indicative of GABA degradation, was found around hair cells, along nerve fibers running through the stroma and within the ganglion cell. These immunocytochemical findings indicate that the GABAergic system exists in the chicken vestibular endorgans and that GABA may function as an afferent neurotransmitter at the level of hair cells.
 ...
PMID:Immunocytochemical study of the GABA system in chicken vestibular endorgans and the vestibular ganglion. 260 15

The technique of estimating gamma-aminobutyric acid (GABA) turnover by inhibiting its major degrading enzyme GABA-T (4-aminobutyrate:2-oxoglutarate aminotransferase; EC 2.6.1.19) and measuring GABA accumulation has been used repeatedly, but, at least in rats, its usefulness has been limited by several difficulties, including marked differences in the degree of GABA-T inhibition in different brain regions after systemic injection of GABA-T inhibitors. In an attempt to improve this type of approach for measuring GABA turnover, the time course of GABA-T inhibition and accumulation of GABA in 12 regions of rat brain has been studied after systemic administration of aminooxyacetic acid (AOAA), injected at various doses and with different routes of administration. A total and rapidly occurring inhibition of GABA-T in all regions was obtained with intraperitoneal injection of 100 mg/kg AOAA, whereas after lower doses, marked regional differences in the degree of GABA-T inhibition were found, thus leading to underestimation of GABA synthesis rates, e.g., in substantia nigra. The activity of the GABA-synthesizing enzyme GAD (L-glutamate-1-decarboxylase; EC 4.1.1.15) was not reduced significantly at any time after intraperitoneal injection of AOAA, except for a small decrease in olfactory bulbs. Even the highest dose of AOAA tested (100 mg/kg) was not associated with toxicity in rats, but induced motor impairment, which was obviously related to the marked GABA accumulation found with this dose. The increase in GABA concentrations induced with intraperitoneal injection of 100 mg/kg AOAA was rapid in onset, allowing one to estimate GABA turnover rates from the initial rate of GABA accumulation, i.e., during the first 30 min after AOAA injection. GABA turnover rates thus determined were correlated in a highly significant fashion with the GAD activities determined in brain regions, with highest turnover rates measured in substantia nigra, hypothalamus, olfactory bulb, and tectum. Pretreatment of rats with diazepam, 5 mg/kg i.p., 5-30 min prior to AOAA, reduced the AOAA-induced GABA accumulation in all 12 regions examined, most probably as a result of potentiation of postsynaptic GABA function. The data indicate that AOAA is a valuable tool for regional GABA turnover studies in rats, provided the GABA-T inhibitor is administered in sufficiently high doses to obtain complete inhibition of GABA degradation.
 ...
PMID:Use of inhibitors of gamma-aminobutyric acid (GABA) transaminase for the estimation of GABA turnover in various brain regions of rats: a reevaluation of aminooxyacetic acid. 280 89

The developmental patterns of gamma-aminobutyric acid (GABA)ergic neurons in primary culture obtained from the neopallium of 15-day-old fetus of mouse were investigated in terms of morphological features, GABA metabolism and GABA receptor binding. Morphological investigations revealed that these cells possessed typical features of neurons and the formation of synapses was detected at 10 days after the inoculation. During neuronal growth on polylysine surfaces, GABA contents and activity of GABA transaminase (GABA-T) showed a progressive increase in the time of culture. Similarly, L-glutamic acid decarboxylase (GAD) showed a progressive elevation during neuronal development in vitro, which corresponded well with the change in immunoreactivity to anti-GAD examined immunohistochemically. In addition, the high K+-evoked release of [3H]GABA also showed an enhancement during the growth in vitro. The numbers of binding sites (Bmax) for [3H]muscimol and [3H]flunitrazepam (FLN) also showed increases with the time of incubation, although affinity (Kd) to the labeled ligands did not show any noticeable changes. Moreover, it was observed that [3H]FLN binding was enhanced by GABA even in neurons cultured for 7 days. These results indicate that cerebral cortical neurons in primary culture possess GABA biosynthesizing and degrading systems including a high-affinity uptake mechanism for GABA. The present results also indicate that these cells possess synaptic contacts as well as GABAA receptors coupled with benzodiazepine receptor from a relatively early stage of cellular development.
 ...
PMID:Development of gamma-aminobutyric acid (GABA)ergic neurons in cerebral cortical neurons in primary culture. 288 49

A severe compression craniocerebral trauma was induced in rats under short-term halothane anesthesia. The activity of pyruvate and 2-oxoglutarate dehydrogenase complexes reduced significantly in the tissue of the damaged hemisphere, ALT activity increased sharply, AST activity grew slowly, the production of GABA in the glutamate decarboxylase reaction was slightly inhibited and its utilization in the GABA transaminase reaction was clearly accelerated. The GABA level in the nerve tissue showed a tendency to reduce, while the glutamate level had a tendency to increase. The observed changes are evidence that the inclusion of the GABA skeleton in the reaction of further oxidation intensifies, which may be of significance in compensation of the transport of the energetically oxidizing succinate and, possibly, in the formation of endogenous GABA possessing a stress-relieving effect.
 ...
PMID:[The compensatory function of a GABA shunt in brain energy metabolism in measured craniocerebral trauma in rats]. 290 62


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>