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)

Synaptic vesicles have been isolated from bovine cerebral cortex by sequential differential and density gradient centrifugations followed by chromatography on a Sepharose 6B column. We have studied the morphology, enzymatic markers, neurotransmitter and ATP contents and protein composition of the vesicles. The specific contents of acetylcholine, gamma-aminobutyric acid, aspartate, glutamate and catecholamines were 4--8-fold higher in the vesicle fraction compared to the crude synaptosomal pellet. Electron micrographs of the vesicle preparation showed enrichment of vesicular material with an average diameter of 50 nm. The purity of the preparation was assessed by the very low activities of enzymatic markers of cellular membranes and cytosol components. Some Ca--Mg-activated ATPase activity was detected in the vesicle preparations, but its content relative to the neurotransmitters fell on chromatography, suggesting that this activity may be partially contributed by non-synaptic vesicle components, such as small microsomes. The isolated synaptic vesicles were solubilized with 1% sodium dodecyl sulfate and subjected to polyacrylamide gel electrophoresis. The major Coomassie blue stained bands observed with apparent molecular weights of 160,000 and 55,000 were enriched in parallel to the increase in purity of the preparation.
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PMID:Studies on synaptic vesicles in mammalian brain characterization of highly purified synaptic vesicles from bovine cerebral cortex. 4 13

The centrally acting drugs belonging to different groups--fluphenazine, trifluperidol, phthoracyzine, imipramine, diazepam, apomorphine, fentanyl, diphneylhydantoin, nonachlazine displayed in vitro an inhibitory effect on the uptake of gamma-aminobutyric acid by rat brain synaptosomes. A decrease in the activity of synaptosomal Na,K-ATPase was found in most cases. Drugs that failed to alter GABA uptake were as a rule found to be ineffective in relation to the enzyme activity (carbidine, morphine). GABA uptake was not affected by certain drugs inhibiting the Na,K-ATPase activity (azabuperon, tetrabenazine). It is supposed that the drugs used had at least two possible sites of action - Na,K-ATPase itself and hypothetic GABA transmembrane carrier.
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PMID:[The effect of psychotropic substances on synaptosomal uptake of gamma-aminobutyric H3-acid and the activity of Na,K-ATPase]. 12 78

The effects of iontophoretically applied Na+-, K+-dependent adenosinetriphosphatase (Na+,K+-ATPase) (EC 3.6.1.3) inhibitors (ouabain, digitoxin, digitoxigenin, strophanthin K, strophanthidin, thevetin A and B, ethacrynate, and harmaline) on the depression of rat cerebral cortical neurones by noradrenaline, 5-hydroxytryptamine, and histamine have been studied. The inhibitors antagonized depressions of spontaneously active neurones evoked by these amines, but not those evoked by gamma-aminobutyric acid, adenosine, adenosine 5'-monophosphate, or calcium. The antagonistic potencies of the various inhibitors appeared to be proportional to their known potencies as inhibitors of Na+, K+-ATPase. The data therefore support the hypothesis that amines depress central neurones by activating an electrogenic sodium pump.
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PMID:Antagonism of biogenic amine-induced depression of cerebral cortical neurones by Na+, K+-ATPase in inhibitors. 14 20

Na,K-ATPase activity in glial membranes is rather low that in the nerve ending membranes, but is characterized by the same kind of Na+/K+-dependence. Glial Na,K-ATPase is insensitive to acetylcholine (ACh), 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) while norepinephrine activates Na,K-ATPase at low concentrations and inhibits it at high concentrations. Participation of Na,K-ATPase in the regulatory mechanisms of the neuron-neuroglia relations is discussed.
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PMID:[Some properties of glial membrane Na, K-ATPase]. 21 27

The aim of the present study was to elucidate the possible functional significance of gamma-aminobutyric acid (GABA) homoexchange at nerve endings. Using synaptosomes from adult rat cerebrum, we found that a number of conditions altering cationic fluxes produced a concomitant change in the stoichiometry of GABA homoexchange, In fact, exogenous GABA (10 muM), while not causing net release of intrasynaptosomal GABA in standard conditions, triggered a large net GABA release in the presence of veratridine, Na(+)-K(+)-ATPase inhibitors, or the ionophore A23187, superimposed on that due to the various agents tested alone. This extra release was mediated by the membrane carrier, being largely inhibited by the GABA carrier-blocker L-diaminobutyric acid. The altered stoichiometry of GABA homoexchange observed under these conditions (efflux > influx) appeared to be coupled to the influx of Na(+) (or of Ca(2+)), rather than determined by the establishment of a high intrasynaptosomal [Na(+)]. Under conditions of reversed Na(+) flux (Na(+) efflux), the GABA outward/inward flux ratio was also reversed, and the stoichiometry of GABA homoexchange was in favor of net influx. The possible contribution of K(+) to the effects observed is also discussed. It is concluded that the GABA transport system of nerve endings is susceptible to fine modulation by changes in cationic fluxes similar to those occurring in vivo during depolarization and repolarization. These fluxes may have a prominent role in determining the direction of net GABA transport in GABA-ergic nerve terminals of the living brain.
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PMID:Modulation of gamma-aminobutyric acid transport in nerve endings: role of extracellular gamma-aminobutyric acid and of cationic fluxes. 35 22

In search of factors mitigating the final outcome of ischemic and epileptic brain damage, we tested a novel dibenzoxazepine derivative (BY-1949), as the compound has been shown to be effective under these two conditions. First, using rat brain, we assessed whether or not BY-1949 affects the Na+,K(+)-ATPase activity. Although in vitro applications of either BY-1949 or its three major metabolites did not cause any apparent effects, both acute and chronic oral administrations of the compound (10 mg/kg) invariably increased the Na+,K(+)-ATPase activity in the synaptosomal plasma membranes by increasing Vmax values. Second, it was shown by this study that the drug treatment caused marked increases in the uptake of both glutamic acid and gamma-aminobutyric acid into the synaptosomes. These results suggest that the activity against ischemic/epileptic brain damage by BY-1949 is explicable, at least partly, in terms of improvement of ionic derangements across the neural membranes via Na+,K(+)-ATPase activation.
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PMID:An activation of synaptosomal Na+,K(+)-ATPase by a novel dibenzoxazepine derivative (BY-1949) in the rat brain: its functional role in the neurotransmitter uptake systems. 134 68

Acute effects of ethanol on Na(+)-dependent transport of gamma-aminobutyric acid (GABA) and glutamic acid (GLU) were investigated in crude synaptosomal preparations from rat cerebral cortex. In experiments with 30-40-day-old (peripubertal) rats, the overall dose responses of the GABA and GLU transport systems to ethanol were biphasic. Stimulation was observed at ethanol concentrations (40-160 mM) relevant to intoxication. Inhibition was observed at higher concentrations of ethanol. The stimulatory phase of the dose response was not observed in 60-100-day-old (adult) rats. In preparations from peripubertal rats, other alcohols also had biphasic dose response curves with stimulation at low alcohol concentrations. The relative efficacy of the different alcohols appeared to correlate with the relative membrane-buffer partition coefficient. In synaptosomal membrane vesicles, where artificial ion concentration gradients rather than Na+,K(+)-ATPase activity provide the driving force for uptake, ethanol did not stimulate GABA uptake. In direct measures of Na+,K(+)-ATPase activity, both Rb+ uptake and ATP hydrolysis were enhanced by 80 mM ethanol. We conclude that stimulation of Na(+)-dependent uptake of amino acids by ethanol was secondary to enhanced Na+,K(+)-ATPase activity and may be associated with a specific developmental stage in the rat.
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PMID:Effects of ethanol on Na(+)-dependent amino acid uptake: dependence on rat age and Na+, K(+)-ATPase activity. 136 Aug 64

A 68-kDa glycoprotein bearing the biological activity of the plasma membrane serotonin (5-hydroxytryptamine, 5-HT) transporter has been purified from human blood platelets, a classical cell model for the study of 5-HT uptake. After treatment of the whole platelet population or its plasma membrane fraction by sulfhydryl-dependent bacterial protein toxins or by digitonin, purification was reproducibly obtained by a one-step affinity chromatography using two different columns with 5-HT or 6-fluorotryptamine as ligands and elution by 5-HT or Na(+)-free buffer. The purified fraction migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single band with an apparent molecular mass of 68 kDa and exhibited an apparent isoelectric point of 5.6-6.2. Two sialic acid residues were detected in the purified material. The purified glycoprotein bound the 5-HT uptake blocker [3H]paroxetine with a Kd (0.25 nM) similar to the one observed for intact human platelets. It also bound [3H] 5-HT but neither [3H]hydroxytetrabenazine nor [3H] ouabain, the respective markers of the granular monoamine transporter and of the Na+,K(+)-ATPase associated to the plasma membrane 5-HT transporter. 5-HT derivatives and 5-HT uptake inhibitors exhibited similar Ki values for 5-HT uptake and paroxetine binding in intact human platelets and in the purified glycoprotein. Under laser UV irradiation, 40% of this purified glycoprotein could be labeled by either [3H]paroxetine or [3H]cyanoimipramine. No labeling was detected with either [3H] gamma-aminobutyric acid or [3H]GBR 12783, the respective markers of gamma-aminobutyric acid and dopamine carriers. The purified 68-kDa protein is therefore likely to correspond at least to the binding domain of the 5-HT transporter located at the human platelet plasma membrane.
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PMID:One-step purification of the serotonin transporter located at the human platelet plasma membrane. 153 59

Granulosa cell lines, transformed by SV40 T-antigen and Ha-ras oncogene, have recently been established that can produce progesterone at levels comparable to those of highly differentiated cultures of primary granulosa cells (1-4). Here, the hypothesis that these cells contain a mitochondrial benzodiazepine receptor, and that stimulation of the receptor can trigger progesterone production in these cells, was tested. The agonist of the peripheral benzodiazepine receptor, Ro5-4864, produced a 3- to 5-fold stimulation (P less than 0.005) of progesterone production both in differentiated granulosa primary cultures and in the oncogene-transformed cell lines. Ro5-2807 (diazepam, Valium) exerts a similar effect on granulosa cell steroidogenesis while the specific agonist of central benzodiazepine receptor Ro15-4513 was without effect. The effects of Ro5-4864 or Ro5-2807 were not additive to those of gonadotropins and cAMP. Intact isolated mitochondria possessed high-affinity binding sites to [3H]-Ro5-4864 (Kd = 3.03 +/- 0.70 nM), which were enriched by 1 order of magnitude in these organelles compared to total cell homogenate. Bound Ro5-4864 could be competitively displaced with 1 microM unlabeled Ro5-4864 and Ro5-2807, but not with specific ligands of central benzodiazepine receptors Ro15-4513 and Ro15-1788. Prolonged elevation of cAMP in these cells caused a 30% (P less than 0.01) rise in the number of receptors. Mitochondria of NIH 3T3 cells contained only 30-40% (P less than 0.001) of the Ro5-4864 binding sites of mitochondria from steroidogenic cells, whereas yeast mitochondria lacked them completely. The existence of functional peripheral benzodiazepine receptors in mitochondria suggests that they may have a physiological role in the mobilization of cholesterol into mitochondria, and in elevating progesterone production in ovarian cells. The modulation of the interaction between benzodiazepine compounds and the gamma-aminobutyric acid receptor by progesterone metabolites suggests new interrelationships between peripheral and central nervous system receptors sensitive to benzodiazepines.
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PMID:An inducible functional peripheral benzodiazepine receptor in mitochondria of steroidogenic granulosa cells. 164 7

In vitro exposure to tetraethyllead (Et4Pb, 10 microM) did not alter the release of [3H] dopamine (DA), [3H]acetylcholine (ACh), or [3H]gamma-aminobutyric acid (GABA) from superfused synaptosomes isolated from rat brain striatum, hippocampus, and cortex, respectively. On the other hand, a concentration-dependent increase in the spontaneous release of these transmitters was observed following exposure to triethyllead (Et3Pb, 0.1-10 microM). The magnitude of 1 microM Et3Pb-induced [3H]DA release was 5-fold greater than that observed for [3H]ACh or [3H]GABA release. Removal of [Ca2+]e did not alter the Et3Pb-induced increase in the release of these three transmitter substances, nor did Et3Pb alter synaptosomal 45Ca efflux. EtePb-induced [3H]ACh and [3H]GABA release, but not [3H]DA release, was blocked by lowering [Na+]e from 140 to 50 mM. Similarly, the release of [3H]ACh and [3H]GABA, but not [3H]DA, induced by either Na,K-ATPase inhibition or veratridine (a Na(+)-ionophore), was attenuated by lowering [Na+]e from 140 to 50 mM. However, Et3Pb did not inhibit isolated synaptic membrane Na,K-ATPase, nor did the magnitude or temporal patterns of Et3Pb-induced transmitter release resemble transmitter release induced by Na,K-ATPase inhibition. Et3Pb and veratridine, but not Na,K-ATPase inhibition, produced an increase in synaptosomal [3H] deoxyglucose phosphate (dGluP) efflux, suggesting that both compounds increase membrane permeability. A Et3Pb-induced increase in membrane permeability is further supported by electrophysiological studies using the frog neuromuscular junction in which Et3Pb was found to reduce both the input resistance and membrane potential of muscle cells. As with [3H]ACh and [3H]GABA release, the Et3Pb-induced increase in synaptosomal [3H]dGluP efflux was attenuated by lowering [Na+]e.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of triethyllead on synaptosomal [3H]dopamine vs. [3H]acetylcholine and [3H]gamma-aminobutyric acid release. 165 96


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