Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.15 (glutamate decarboxylase)
 2,169 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histochemical and biochemical studies demonstrate that gamma-aminobutyric acid (GABA), glutamic acid decarboxylase (EC 4.1.1.15), and GABA aminotransferase (EC 2.6.1.19) are present in bovine adrenal chromaffin cells. Moreover, [3H]GABA can be taken up and stored by primary cultures of adrenal chromaffin cells. Nicotinic receptor stimulation or KCl depolarization releases the [3H]GABA taken up by these cell cultures. GABA and benzodiazepine recognition sites located in chromaffin cells interact with each other with modalities similar to those described for GABA and benzodiazepine recognition sites located in synaptic membranes prepared from brain tissue. Bicuculline facilitates the release of catecholamine from chromaffin cells induced by nicotinic receptor stimulation but it fails to influence the release of catecholamine evoked by K+ depolarization. Since the GABA-benzodiazepine receptor system appears to modulate nicotinic receptor function, it is suggested that GABA transmission might participate in modulating responsiveness of chromaffin cells to incoming cholinergic stimuli.
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PMID:Intrinsic GABAergic system of adrenal chromaffin cells. 632 6

Purkinje neurons of the cerebellar cortex from a chemically and morphologically heterogeneous population containing some members that have gamma-aminobutyric acid (GABA), others that have immunoreactivity for motilin, and a small number that have both. The remaining 30-40% of all Purkinje cells have neither of these two neuroactive substances, leaving possibilities for other transmitter candidates. The evidence was compiled from double-staining immunocytochemical procedures performed on single sections of the cerebellum and brain stem in rat, mouse, and monkey. Two polyclonal antibodies were applied in succession, one directed against the midregion and COOH terminus of the 22-amino acid polypeptide motilin and the other against glutamic acid decarboxylase (glutamate decarboxylase; L-glutamate 1-carboxy-lyase, EC 4.1.1.15), the rate-limiting enzyme in the synthesis of the neurotransmitter GABA. The staining combinations employed the immunoperoxidase method, with different chromogens for distinguishing the motilin-like immunoreactivity from glutamic acid decarboxylase immunoreactivity by different colors, or the immunoperoxidase method for one antiserum and immunofluorescence for the other. The locations of both motilin and GABA cell types were mapped. The recognition of motilin in Purkinje cells calls for experimental definition of the role of this substance in the cerebellum and for reevaluation of the roles of Purkinje cells and of GABA in cerebellar function. The significant motilin representation in the flocculus, paraflocculus, and vermis suggests that it may be the Purkinje cell mediative chemical in the vestibular parts of the cerebellum. However, the presence of GABA as well in the same regions indicates that the chemical preference may be at least bimodal.
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PMID:Chemical heterogeneity in cerebellar Purkinje cells: existence and coexistence of glutamic acid decarboxylase-like and motilin-like immunoreactivities. 703 82

The comparative effects of a 10 day estrogen treatment and estrogen independent hyperprolactinemia on nigral and striatal glutamic acid decarboxylase (GAD, EC 4.1.1.15) activity were investigated in male rats. Data obtained show that estrogen treatment decreases GAD activity in substantia nigra, while an increase was observed in conditions of hyperprolactinemia induced by adenohypophysis homograft or acute and chronic sulpiride injection. The possibility of an opposite modulation of strio-nigral GABAergic system by estrogens and prolactin is suggested.
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PMID:Comparative effects of estrogens and prolactin on nigral and striatal GAD activity. 705 6

The AA. have investigated the effects of acute or chronic injection of typical and atypical antidepressants on the activity of the GABA--synthesizing enzyme glutamic acid decarboxylase (GAD, EC 4.1.1.15) in discrete brain regions. Very significant changes in GAD activity were only observed with sulpiride and nomifensine, two atypical antidepressants that selectively influence dopaminergic transmission and, in turn, prolactin secretion.
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PMID:Effects of some typical and atypical antidepressants on GAD activity in various brain regions. 709 72

The effects of gamma-aminobutyric acid (GABA)-alpha-oxoglutarate aminotransferase (GABA-T) inhibitors, L-glutamic acid decarboxylase (GAD) inhibitors, and antipetit mal anticonvulsants on gamma-hydroxybutyric acid (GHB) and GABA were studied. Treatment with anticonvulsants and GABA-T inhibitors resulted in an increase in steady-state brain levels of both GHB and GABA. GAD inhibitors produced markedly decreased levels of brain GABA but no change in GHB concentrations. Studies of GHB derived exclusively from GABA showed that GABA-T inhibitors which produced an elevation of steady-state levels of GHB in brain also resulted in a decrease in GABA-derived GHB. Intracerebroventricular (i.c.v.) administration of GABA, putrescine, and 1,4-butanediol all produced significant elevations in brain GHB, but GABA-T inhibitors blocked this effect of GABA and putrescine. These data suggest that there may be another source for GHB in brain in addition to GABA and raise the possibility that 1,4-butanediol may be that source.
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PMID:Studies on the relation of gamma-hydroxybutyric acid (GHB) to gamma-aminobutyric acid (GABA). Evidence that GABA is not the sole source for GHB in rat brain. 715 69

The activity of gamma-aminobutyric acid (GABA) synthesizing enzyme glutamic acid decarboxylase (GAD, EC 4.1.1.15) was assayed in the rat substantia nigra (SN) and medial basal hypothalamus (MBH) following systemic injection of different doses of the dopamine receptor agonist apomorphine. In SN, the highest dose of apomorphine (1000 micrograms/kg) causes an increase of the GAD activity whilst an opposite effect is observed with the lowest dose (35 micrograms/kg). Results obtained in SN are in accordance with previous neurochemical and behavioural data suggesting an opposite action of high (500 micrograms/kg) and low doses (100 micrograms/kg) of apomorphine in nigro-striatal system, probably due to the existence of two classes of dopamine receptors, i.e. classical postsynaptic dopamine receptors and presynaptic inhibitory dopamine autoreceptors. In MBH, the evidence for similar effects of low and high doses of apomorphine (the decrease of GAD activity) may suggest that, as already reported, at this level only one class of dopamine receptors is present.
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PMID:[Effects of different doses of apomorphine on the glutamate decarboxylase activity of the substantia nigra and the medial basal hypothalamus]. 731 1

The effects of different doses of the dopamine (DA) receptor agonist apomorphine on the activity of the gamma-aminobutyric acid (GABA)-synthesizing enzyme glutamic acid decarboxylase (GAD, EC 4.1.1.15) were investigated in rat substantia nigra in comparison with haloperidol and sulpiride, two DA receptor blocking agents. Results obtained show that low doses (10,35 microgram/kg, s.c.) of apomorphine induce a decrease in nigral GAD activity whilst an opposite effect is observed with the highest dose (1000 microgram/kg, s.c.). No significant change is observed following injection of the intermediate doses (100 and 500 microgram/kg, s.c.). Moreover, sulpiride at the dose used (2 mg/kg, i.p.) induces an increase in GAD activity whilst no effect follows systemic injection of the same dose of haloperidol. The results are discussed in light of recent neurochemical and behavioral data.
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PMID:Effects of different doses of apomorphine on GAD activity in rat substantia nigra. 734 53

Disruption of dopaminergic neurotransmission in the striatum by neurotoxic lesions of the substantia nigra leads to increases in glutamic acid decarboxylase and proenkephalin messenger RNA expression, and to decreases in preprotackykinin (the precursor molecule for substance P) messenger RNA expression in the two populations of striatal medium-sized spiny projection neurons. These cells also express TrkB, the neurotrophin receptor for brain-derived neurotrophic factor and neurotrophin 4/5, and TrkC, the receptor for neurotrophin-3. Since there is some indication that exogenous brain-derived neurotrophic factor can exert neuromodulatory effects in the basal ganglia, we studied the effects of repeated intrastriatal injections of the four members of the neurotrophin family of neural growth factors, nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 on the expression of striatal neurotransmitter-related genes in the unilaterally 6-hydroxydopamine-lesioned rat using in situ hybridization histochemistry. We found that 4 micrograms/day of brain-derived neurotrophic factor or neurotrophin-4/5 when injected intrastriatally for eight consecutive days led to a normalization of the denervation-induced decrease of preprotachykinin messenger RNA when compared to animals injected with equivalent doses of nerve growth factor, neurotrophin-3, or vehicle. Neurotrophin-4/5 alone also normalized expression of messenger RNA encoding the 67 x 10(3) mol. wt isoform of glutamate decarboxylase, while none of the neurotrophins had a significant effect on preproenkephalin messenger RNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Brain-derived neurotrophic factor and neurotrophin-4/5 modify neurotransmitter-related gene expression in the 6-hydroxydopamine-lesioned rat striatum. 761 69

The postnatal development of direct thalamocortical projections from the zona incerta of the ventral thalamus to the whisker representation area of the rat primary somatosensory cortex was investigated. Cytoarchitectonic analysis based on Nissl staining, cytochrome oxidase histochemistry and immunohistochemistry for glutamic acid decarboxylase, GABA, parvalbumin and calbindin D28K revealed that the zona incerta can be clearly distinguished from surrounding diencephalic structures from the day of birth. Moreover, four distinct anatomical subdivisions of this nucleus were identified: the rostral, dorsal, ventral and caudal. Of these, the ventral subdivision is by far the most conspicuous, containing the highest density of neurons, and the highest levels of cytochrome oxidase, glutamate decarboxylase, GABA, parvalbumin and calbindin D28K. In contrast, the dorsal, rostral and caudal subdivisions contain fewer cells, lower levels of glutamic acid decarboxylase and GABA and very few parvalbumin-positive and calbindin-positive neurons. Small injections of rhodamine coated microspheres or Fluoro-gold in the primary somatosensory cortex of animals at different stages of development revealed the existence of retrogradely labeled neurons in the rostral and dorsal subdivisions of the zona incerta from postnatal day 1. At this age, retrogradely labeled cells were also found in the ventral lateral, ventral posterior medial, posterior medial, centrolateral, ventral medial and magnocellular subdivision of the medial geniculate nuclei of the dorsal thalamus. The density of the incertocortical projection reaches its maximum between the first and second postnatal weeks, decreasing subsequently, until an adult pattern of labeling is achieved. Tracer injections combined with immunohistochemistry revealed that the majority of the incertocortical projection derives from GABAergic neurons, implying a potentially inhibitory role for the incertocortical projection. These results demonstrate that the rat trigeminal system contains parallel thalamocortical pathways of opposite polarity, emerging from both the dorsal (glutamatergic, excitatory) and ventral (GABAergic, inhibitory) thalamus since the day of birth. As such, these findings suggest that, contrary to the classical notion, not only the dorsal but also the ventral thalamus may play a special role in both cortical maturation and function.
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PMID:Development of direct GABAergic projections from the zona incerta to the somatosensory cortex of the rat. 777 73

It has been shown that the enzyme glutamic acid decarboxylase (GAD; EC 4.1.1.15), which catalyzes the conversion of L-glutamate to gamma-aminobutyric acid in the central nervous system of vertebrates, can be first detected in rodents at late embryonic stages. In contrast, we have found that the gene coding for the 67-kDa form of GAD is already transcriptionally active at embryonic day E10.5 in the mouse. In addition to the 3.5-kb adult-type mRNA, we have detected two 2-kb embryonic messages that contain alternatively spliced exons of 80 (I-80) and 86 (I-86) bp, respectively. The overlapping stop-start codon TGATG, found in the embryonic exons, converts the monocistronic adult-type transcript into a bicistronic one, coding for a 25-kDa leader peptide and a 44-kDa enzymatically active truncated GAD. A second stop codon at the 3' end of the 86-bp exon abolishes the expression of truncated GAD. The products of the two embryonic mRNAs were identified in a rabbit reticulocyte in vitro translation system, COS cells, and mouse embryos. The two GAD embryonic forms represent distinct functional domains and display characteristic developmental patterns, consistent with a possible role in the formation of the gamma-aminobutyric acid-ergic inhibitory synapses.
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PMID:Distinct protein forms are produced from alternatively spliced bicistronic glutamic acid decarboxylase mRNAs during development. 793 69


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