Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamate stimulated release of [3H]GABA was studied, during receptor desensitization block and its modulation by voltage gated Ca2+ channels, internal Ca2+ mobilization and GABA transport inhibitors from olfactory bulb slices. Under control conditions, glutamate and agonists induced release was strongly inhibited by Mg/0 Ca2+ Krebs and Cd2+ and partially inhibited by Ni2+ and nifedipine. Cyclothiazide, which blocks desensitization of glutamate receptors, potentiated glutamate, kainate, AMPA and quisqualate induced release. This effect was less dependent of entry of external Ca2+, but was inhibited by trifluoperazine and thapsigargin, inhibitors of Ca2+-calmodulin and endoplasmatic Ca2+ ATPase respectively. Nipecotic acid and NO-711, inhibitors of the GABA transporter, were also able to reduce cyclothiazide potentiated release induced by the 4 secretagogues. Under control conditions, glutamate stimulates the release of GABA in cooperation with VDCC. However, during receptor desensitization block, glutamate stimulated GABA release is mainly modulated through mechanisms dependent on internal Ca2+ mobilization and reversal of the GABA transporter.
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PMID:Glutamate receptor desensitization block potentiates the stimulated GABA release through external Ca2+-independent mechanisms from granule cells of olfactory bulb. 1187 98

Activation of muscarinic cholinergic receptors produces oscillations in the hippocampal slice that resemble the theta rhythm, but also may produce abnormal synchronous activity that is more characteristic of epileptiform activity. We used pilocarpine, a muscarinic agonist and convulsant, and an elevation in extracellular potassium (5-7.5 mM) to produce synchronous neuronal activity that was prolonged (>2 s) and mimicked synchronization noted during seizures in vivo (ictal activity). In the CA3 region of adult rat hippocampal slices, prolonged ictal oscillations consisted of rhythmic field potentials occurring at 4-10 Hz for up to 30 s (ictal duration) that occurred in a regular periodic pattern every 12-166 s (ictal interval). The duration and interval between ictal oscillations were measured before and after application of drugs to define determinants of ictal occurrence. High threshold calcium channel antagonists (nifedipine and verapamil) blocked ictal activity. Release of calcium from intracellular stores also appeared to be important for ictal synchronization because ictal activity was blocked by dantrolene, an inhibitor of calcium release from intracellular stores, and by thapsigargin which blocks the ATPase that maintains intracellular calcium stores. These suppressive effects appeared to be postsynaptic because nifedipine, dantrolene, and thapsigargin had no effect on evoked fEPSPs. Enhancement of presynaptic inhibition by activation of GABA(B) or adenosine A(1) receptors suppressed ictal activity and depressed the amplitude of evoked population synaptic potentials. The results point to an important role for high threshold calcium channels and release of calcium from intracellular stores in addition to strength of synaptic connections in generation of prolonged oscillations that underlie seizure activity.
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PMID:Suppression of pilocarpine-induced ictal oscillations in the hippocampal slice. 1194 8

1. Miniature inhibitory postsynaptic currents (mIPSCs) were recorded in mouse Purkinje cells in the presence of 1 micro M tetrodotoxin (TTX). Under these conditions, which eliminated Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCCs), the contribution of Ca(2+) stores to spontaneous GABA release was examined. 2. The plant alkaloid ryanodine acts as an inhibitor of endoplasmic reticulum ryanodine-sensitive Ca(2+) release channels (ryanodine receptors) at low micromolar concentrations. Ryanodine effects were confined to a subpopulation of cells tested. At 10 micro M ryanodine, 4/12 cells showed a significant increase in mean mIPSC frequency of +19.6+/-4.0% (n=4). 3. The sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) pump inhibitor cyclopiazonic acid (CPA) produced a more robust effect. In 8/10 cells, 25 micro M CPA caused a significant increase in mean mIPSC frequency; the mean increase being +26.0+/-3.0% (n=8). Similar results were seen with thapsigargin (1-2 micro M), another SERCA pump inhibitor. 4. Ruthenium red (RuR) has been proposed to either act directly on the release machinery or block Ca(2+) pumps on internal stores. At 10 micro M RuR, all cells showed a rapid, large increase in mean mIPSC frequency of +90.4+/-16.4% (n=9). This increase was greater than that seen by agents known to modulate Ca(2+) stores and was more consistent with a direct action. At this concentration, RuR also occluded the effects of CPA. 5. For all reagents, there were no obvious effects on mean mIPSC amplitude. However, the effects on mIPSC frequency were consistent with a presynaptic action and indicate that Ca(2+) stores may contribute to spontaneous GABA release onto mouse Purkinje cells.
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PMID:Presynaptic internal Ca2+ stores contribute to inhibitory neurotransmitter release onto mouse cerebellar Purkinje cells. 1235 35

Neurofibromatosis 1 is one of the most common single-gene disorders affecting neurologic function in humans. Mutations in the NF1 gene cause abnormalities in cell growth and differentiation and lead to a variety of learning disabilities. Neurofibromin has several biochemical functions, such as Ras-guanosine triphosphatase activity, adenylate cyclase modulation, and microtubule binding, all of which could be critical for brain function. We review how studies in mouse models are helping to unravel the molecular and cellular mechanisms underlying cognitive deficits in neurofibromatosis 1. These studies suggest that the learning disabilities associated with neurofibromatosis 1 are caused by excessive Ras activity that leads to increased gamma-aminobutyric acid (GABA(A)) inhibition and to decreased long-term potentiation. These findings have brought us closer than ever to the development of possible treatments for the learning disabilities associated with neurofibromatosis 1.
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PMID:Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1. 1240 61

The SLC32 family comprises a single member: the vesicular inhibitory amino acid transporter (VIAAT) or vesicular GABA transporter (VGAT). It belongs to a eukaryotic-specific superfamily of H(+)-coupled amino acid transporters, which also comprises the mammalian SLC36 and SLC38 transporters. VIAAT exchanges GABA or glycine for protons. It is present on synaptic vesicles of GABAergic and glycinergic neurons, and in some endocrine cells, where it ensures the H(+)-ATPase-driven uptake, and subsequent exocytotic release, of inhibitory amino acids. Despite a similar function in vesicular neurotransmitter loading, VIAAT is not related to the vesicular glutamate transporter (VGLUT, SLC17) or the vesicular monoamine transporter/vesicular acetylcholine transporter (VMAT/VACHT, SLC18) proteins.
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PMID:The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids. 1275 Aug 92

In a previous study, we suggested that GABAergic neurons might be resistant to ischemic insult, because of the maintenance of the GABA shunt, which is one of the ATP synthetic pathways in neurons. In the present study, we identified Na(+)-K(+) ATPase immunoreactivity in the gerbil hippocampus in order to determine whether changes in Na(+)-K(+) ATPase immunoreactivity correlate with GABA shunt following ischemic insult. At 12 h after ischemia-reperfusion, Na(+)-K(+) ATPase immunoreactivity accumulated in some neurons in the CA1 region. However, the protein content of Na(+)-K(+) ATPase was not altered. Interestingly, the density of Na(+)-K(+) ATPase immunoreactivity in neurons and the protein content in the CA1 region was intensified in the 24 h post-ischemic group. As a result of double immunofluorescence study, Na(+)-K(+) ATPase immunoreactive neurons were identified with GABAergic neurons. Therefore, our findings suggest that the increase of Na(+)-K(+) ATPase in GABAergic neurons may be able to explain the resistance of these cells to ischemic insult, and support our previous hypothesis that GABA may play an important role as a metabolite in the survival of GABAergic neurons after ischemic insult.
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PMID:Elevation of Na+-K+ ATPase immunoreactivity in GABAergic neurons in gerbil CA1 region following transient forebrain ischemia. 1283 89

We have previously shown that the membrane-associated form of the GABA-synthesizing enzyme, glutamate decarboxylase 65 (GAD(65)), is activated by synaptic vesicle proton gradient-mediated protein phosphorylation. We now report that the rate-limiting enzyme in dopamine (DA) biosynthesis, tyrosine hydroxylase (TH), is regulated similarly to GAD(65). The membrane-associated form of TH (MTH) was activated by conditions favoring protein phosphorylation (e.g. ATP) and was inhibited by phosphatase (e.g. calf intestine phosphatase). Furthermore, the ATP-mediated activation of MTH was abolished by conditions that disrupted the proton gradient of synaptic vesicles, e.g. the presence of carbonyl cyanide M-chorophenylhydrazone, gramicidin, or the V-type ATPase inhibitor (bafilomycin), but not the P-type ATPase inhibitor (vanadate). Moreover, DA newly synthesized from tyrosine by MTH and membrane-associated aromatic amino acid decarboxylase was taken up preferentially rather than pre-existing DA. Therefore, the previously proposed model showing close coupling between GABA synthesis and GABA packaging into synaptic vesicles by vesicular GABA transporters is also applicable to the DA system. Hence, it is concluded that there is a general coupling mechanism between neurotransmitter synthesis and packaging of transmitter into synaptic vesicles.
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PMID:Demonstration of functional coupling between dopamine synthesis and its packaging into synaptic vesicles. 1463 Nov 17

Isolated studies showed that norepinephrinergic REM-OFF neurons are active throughout except during rapid eye movement (REM) sleep when they are inhibited possibly by GABA. Similarly, independent studies have also reported that during REM sleep deprivation those REM-OFF neurons continue firing, that there is increased norepinephrine (NE) in the brain and that increased levels of NE increases the Na-K ATPase activity in the brain. However, it was not known if all those changes were directly related to REM sleep deprivation, what could be the mechanism for such changes and their patho-physiological significance. To confirm the same, based on the reports, mostly from our group, it was hypothesised that GABA antagonist in the locus coeruleus (LC) should at least significantly reduce REM sleep and simultaneously increase Na-K ATPase activity in the brain. To confirm the proposed hypothesis, picrotoxin, a GABA-A receptor antagonist, was bilaterally microinjected every 6 h for 36 h into the LC of freely moving normally behaving rats and the effects on electrophysiological signals signifying sleep-wakefulness and on brain synaptosome Na-K ATPase activity were estimated. The microinjection was done with the help of a remote control pump without handling or disturbing the rats. The findings that REM sleep was significantly reduced and there was associated increase in Na-K ATPase activity confirmed our hypothesis. The results also support our modified (GABA-mediated) model of neural connections in the LC for the regulation of REM sleep. Also, this is probably the first report to simulate REM sleep deprivation using receptor antagonist.
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PMID:Long term blocking of GABA-A receptor in locus coeruleus by bilateral microinfusion of picrotoxin reduced rapid eye movement sleep and increased brain Na-K ATPase activity in freely moving normally behaving rats. 1508 34

Corelease of glycine and GABA from the single synaptic terminal (synaptic bouton) is well accepted in immature rat spinal cord and brainstem. However, it raises the question of how glycine and GABA are accumulated in the same synaptic vesicles and coreleased. To address this issue, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) and focally evoked IPSCs (eIPSCs) mediated via a single synapse were recorded from synaptic bouton preparations of the rat immature sacral dorsal commissural nucleus (SDCN) neurones by whole-cell patch recording. Focal stimulation of a single synaptic bouton revealed that three different quantal releases occur from a single synaptic bouton: i.e. pure glycine, pure GABA, and mixed. Prolonged treatment with bafilomycin A1, a vacuolar-type H+/ATPase inhibitor, to the SDCN neurone greatly suppressed frequency and amplitude of the mIPSCs. During washing out of bafilomycin A1, complete recovery in the amplitude of glycinergic mIPSCs was observed, while that of GABAergic and mixed mIPSCs was incomplete. These observations indicate that three types of vesicles coexist in single synaptic terminals, and that refilling of glycine into the synaptic vesicle predominantes over GABA after pretreatment with bafilomycin A1 in immature rats. This could be explained by the decrease in the cytosolic concentration of GABA, or by the presence of subtypes of vesicular inhibitory amino acid transporter in the synaptic vesicle membrane.
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PMID:Distinct profiles of refilling of inhibitory neurotransmitters into presynaptic terminals projecting to spinal neurones in immature rats. 1530 81

We studied the combined effect of diazepam and GABAA-ergic ligands on the activity of Cl- -ATPase from plasma membrane of bream brain. of The membranes were preincubated and incubated with diazepam as well as with other GABAA-ergic ligands at physiological pH (7.4), i.e. under the conditions when Cl- -ATPase activity is undetectable. GABA (0.1-100 microM) induced Cl- -ATPase activity with the maximum effect at 10 microM. Diazepam (0.1 microM) enhanced the effect of low GABA concentrations (0.1-1 microM) on Cl- -ATPase activity but had no effect on the enzyme in the presence of high GABA concentrations (10-100 microM). At the same time, GABA (1 microM) enhanced the effect of low diazepam concentrations (0.1-1 microM) on the enzyme activity but had no effect on it in the presence of high concentrations of the ligand. Blockers of GABAA-ergic receptors, picrotoxin (50 microM) and bicuculline (5 microM), canceled the combined effect of diazepam and GABA on the enzyme activity. The obtained data demonstrate that the combined effect of diazepam and GABAA-ergic ligands on Cl- -ATPase activity at physiological pH is similar to the effect of these ligands on GABAA/benzodiazepine/Cl- channel.
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PMID:[Combined effect of diazepam and GABAA-ergic ligands on the activity of Cl(-)-ATPase from plasma membrane of bream brain (Abramis brama L.)]. 1535 56


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