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)

Our efforts have been directed towards characterizing amino acid uptake, metabolism and release in bulk-isolated glia and neuronal perikarya studied in parallel with nerve-endings, especially as it concerns the transmitter amino acids and the participation of glia in the clearing of the synpatic space during impulse conduction. A possible neuromodulator role for the glia at the synapse is also suggested by K+-stimulated release. Our most definitive conclusions have been based so far on studies with GABA, although we are also beginning to accumulate data for glutamate related to glutamate-glutamine compartmentation. Glia preferentially accumulate potassium and amino acids compared to neuronal perikarya, have higher Na+/K+-ATPase activity, possess high-affinity, sodium-dependent uptake systems for GABA and glutamate similar to the ones in synaptosomes, and release amino acid in response to a potassium pulse by a calcium-independent process. Low neuronal uptake could be due to loss of dendrites. Unidirectional GABA-flux from the synaptosomal to glial compartment is supported by high GAD in nerve endings compared to high GABA-T in glia. Glutamine may be a transmitter glutamate-precursor in nerve-endings since glutaminase activity is high in nerve-endings, but low in glia where glutamine is presumably made. Glutamine uptake in both glia and synaptosomes obeys low-affinity kinetics in contrast to glutamate, consistent with the inability of glutamine to excite the neuronal membrane. The studies with GABA, which are considerably more extensive, are supported by related work using glia in tissue-culture and autoradiography. There appears to be a suggested difference in the behavior of amines which were poorly taken up by the glial system. Glia, synaptosomes and neuronal perikarya, in general behaved similarly with respect to requirements for uptake and release, except in the case of Ca++, which exerted opposite effects on glial and synaptosomal uptake of GABA. We believe that work along these lines tends to firmly establish a direct role for glial cells as modulators of neuronal excitability and represents a convergence between transmitter amino acid neuropharmacology and cellular biochemistry. This not only deepens and enlarges the vocabulary of synaptic biochemistry but also undoubtedly will have major clinical applications in the fields of epilepsy and behavior.
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PMID:Amino acid transport in isolated neurons and glia. 0 26

Bilateral occlusion of common carotid arteries in Mongolian gerbils was produced for the periods (up to 15 min) which were shown to be totally reversible. There was an initial increase of cyclic AMP and GABA levels and enhanced activities of adenylate cyclase and glutamate decarboxylase, as well as the reduction of norepinephrine level and decreased activities of monoamine oxidase, GABA-transaminase and Na+-K+-ATPase. Following these changes, decreased concentration of dopamine, serotinin and glutamate were found. The activities of total protein kinase and acetylcholinesterase were found to be reduced after longer periods of short-term ischemia. The data are consistent with the concept of increased non-controled release of putative neurotransmitters in ischemia.
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PMID:Alterations of putative neurotransmitters and enzymes during ischemia in gerbil cerebral cortex. 3 75

Chronic ammonia toxicity in experimental mice was induced by exposing them for 2 and 5 days to 5 % (v/v) ammonia solution. The enzymes concerned with glutamate metabolism (aspartate-, alanine- and tyrosine aminotransferases, glutamate dehydrogenase and glutamine synthetase) and (Na+ + K+)-ATPase were estimated in the three regions of brain (cerebellum, cerebral cortex and brain stem) and in liver. Glutamate, aspartate, alanine, glutamine and GABA, RNA and protein were also estimated in the three regions of brain and liver. A significant rise in the activity of (Na+ + K+)-ATPase in all the three regions of brain along with a fall in the activity of alanine aminotransferase was noticed. Changes in the activities of other enzymes were also observed. A significant increase in alanine and a decrease in glutamic acid was observed while no change was observed in the content of other amino acids belonging to the glutamate family. As a result of this, changes in the ratios of glutamate/glutamine and glutamate + aspartate/GABA was observed. The results indicated that the brain was in a state of more depression and less of excitation. Under these conditions the liver tissue was showing a profound rise in the activity of the enzymes of glutamate metabolism. The results are further discussed.
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PMID:Chronic metabolic effects of ammonia in mouse brain. 9 19

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

ATPase activities were studied in brain, kidney and liver (13,000 X g pellet) fraction from the mouse. Dopamine and norepinephrine added in vitro showed a dose-dependent stimulation of Na+ and K+ activated and oligomycin sensitive Mg2+ ATPase activities in brain but not kidney and liver tissue fractions. GABA and serotonin had no effect on ATPase in brain, but inhibited oligomycin sensitive Mg2+ ATPase activities in kidney and liver. The relationship between the enhancement of ATPase activity by neurotransmitters in brain and the neuronal excitation is discussed.
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PMID:Effect of biogenic amines and GABA on ATPase activities in mouse tissue. 13 59

The efflux of [3H]glycine was studied in superfused rabbit retina in the presence of various amino acids, ouabain, or high K+ or low Ca2+ concentrations in the superfusion medium. Unlabelled glycine evoked an accelerated efflux as did the structurally similar neutral alpha-amino acids. beta-alanine and GABA were ineffective. The results demonstrate a homoexchange of glycine, and a heteroexchange with the neutral alpha-amino acids. A low concentration of glutamic acid (10(-5) M) will release glycine from the retina. This is an ATPase dependent process which is partially blocked by a high Mg2+/Ca2+ ratio and which may be related to a retinal transmitter function of glutamic acid. A high concentration of K+ or the presence of ouabain in the superfusing medium greatly increases the rate at which glycine is lost from the retina.
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PMID:Factors affecting the spontaneous release of (3H)glycine from rabbit retina. 57 47

The in vitro effects of some neuroleptics and antidepressants on the accumulation of [3H]/-GABA by the synaprosomes of the rat brain cortex were studied. Chloropromazine, trifluoperazine, fluphenazine, perphenazine, thioproperazine, haloperidol, trifluperidol, droperidol, imipramine, haloanison and phthoracyzine were found (in order of a decreasing activity) to inhibit the [3H]/-GABA uptake of synaptosomes. Neuroleptics, except for a new drug carbidine, proved to be more potent inhibitors than antidepressants are. The tranquilized diazepan failed to have any effect on the [3H]/-GABA uptake. The rats synaptosomes treated with chlorpromazine and imipramine were found to display a decreased ability to accumulate [3H]/-GABA. The suppressive effect of psychotropic agents on the [3H]/-GABA uptake by synaptosomes is suggested to be due, at least partly, to their known inhibitory influence on the Na+, K+-dependent ATPase.
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PMID:[Effect of psychotropic substances on the uptake of [H3]-gamma-aminobutyric acid by rat brain synaptosomes]. 118 82

A long period of experimental work has led to the conclusion that Na+/K(+)-ATPase is the enzymatic version of the Na+/K+ pump. This enzymatic system is in charge of various important cell functions. Among them cationic equilibrium and recovering of resting membrane potential in neurons is relevant. A tetrameric ensemble of peptides conform the system known as alpha and beta subunits. The alpha subunit is subdivided in alpha 1, alpha 2 and alpha 3, according to different location and properties. Regulatory factors intrinsic to the Na+/K(+)-ATPase system are: ATP, Na+ and Mg2+ concentrations inside the cell, and K+ outside. The enzyme activity is also regulated by extrinsic factors like some hormones (insulin and thyroxine). Induction of gene expression or post-translational modifications of the preexisting pool of the enzyme are the basic mechanisms of regulation proposed. Other extrinsic factors that seem to regulate the enzyme activity are some neurotransmitters. Among them the most extensively studied are catecholamines, mainly norepinephrine (NE) and lately serotonin (5-HT). The mechanism suggested for NE activation of the enzyme seems to involve specific receptors or a non-specific chelating action related to the catechol group that would relieve the inhibition by divalent cations. Another possibility is that NE removes an endogenous inhibitory factor present in the cytoplasm. The Na+/K(+)-ATPase is activated also by 5-HT. In vivo pharmacological and nutriological manipulations of brain 5-HT are accompanied by parallel responses of Na+/K(+)-ATPase activity. Serotonin agonists do activate the enzyme and antagonists neutralize the activation. In vitro there is a different dose dependent activation, according to the brain region. The mechanism involved seems to implicate a specific receptor system. Serotonin-Na+/K(+)-ATPase interaction in the rat brain is probably of functional relevance because it disappears in amygdaloid kindling. Also it seems to influence the ionic regulation of the pigment transport mechanism in crayfish photoreceptors. In relation to other neurotransmitters, a weak response to histamine was observed with acetylcholine, GABA and glutamic acid, the results were negative.
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PMID:Na+/K(+)-ATPase regulation by neurotransmitters. 136 8

The gamma-aminobutyric acid transporter of rat brain synaptic vesicles was reconstituted in proteoliposomes, and its activity was studied in response to artificially created membrane potentials or proton gradients. Changes of the membrane potential were monitored using the dyes oxonol VI and 3,3'-diisopropylthiodicarbocyanine iodide, and changes of the H+ gradient were followed using acridine orange. An inside positive membrane potential was generated by the creation of an inwardly directed K+ gradient and the subsequent addition of valinomycin. Under these conditions, valinomycin evoked uptake of [3H]GABA which was saturable. Similarly, [3H]glutamate uptake was stimulated by valinomycin, indicating that both transporters can be driven by the membrane potential. Proton gradients were generated by the incubation of K(+)-loaded proteoliposomes in a buffer free of K+ or Na+ ions and the subsequent addition of nigericin. Proton gradients were also generated via the endogenous H+ ATPase by incubation of K(+)-loaded proteoliposomes in equimolar K+ buffer in the presence of valinomycin. These proton gradients evoked nonspecific, nonsaturable uptake of GABA and beta-alanine but not of glycine in proteoliposomes as well as protein-free liposomes. Therefore, transporter activity was monitored using glycine as an alternative substrate. Proton gradients generated by both methods elicited saturable glycine uptake in proteoliposomes. Together, our data confirm that the vesicular GABA transporter can be energized by both the membrane potential and the pH gradient and show that transport can be achieved by artificial gradients independently of the endogenous proton ATPase.
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PMID:Functional reconstitution of the gamma-aminobutyric acid transporter from synaptic vesicles using artificial ion gradients. 168 90

The membrane potential and membrane input resistance of cortical astrocytes from newborn mice were recorded with and without exposure to 1 mM barium. Barium treatment drastically decreased the membrane response to 0 and 35 mM K+. It also revealed an electrogenic component of the Na+,K(+)-ATPase as evident by a biphasic depolarization as a response to ouabain, which was monophasic without barium presence. Untreated mouse astrocytes reacted with small monophasic depolarizations to GABA and glutamate exposure. Barium-treated astrocytes exhibited additional transient responses to both transmitters, similar to those responses of rat astrocytes as found in the literature. The transmitter responses were not changed by exposure to uptake blockers for both transmitter substances. Thus, this electrophysiological study confirms earlier studies with radioactive K+ fluxes in showing that astrocytes derived from mouse brain are capable of short-circuiting electrogenic components and transmitter responses. This extreme high K+ permeability resembles the one reported for endfeet of retinal Muller cells and dissociated astrocytes from optic nerve.
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PMID:Short-circuiting effects of K+ currents on electrical responses of type-1-like astrocytes from mouse cerebral cortex. 168 27


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