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)

Catecholamine (CA) release was studied in rat adrenal incubated in vitro. Inhibition of (Na + K)-ATPase either by omission of K+ from the incubation medium or by addition of a high concentration of ouabain (10(-3) M) caused increased release of CA from the adrenal. Diphenylhydantoin (DPH) (10(-5) M) inhibited the spontaneous as well as the acetylcholine (10(-4) M)-induced release of CA. However, in K+-free medium or in the presence of 10(-3) M ouabain, DPH had no significant effect on CA release. A low concentration of ouabain (10(-10) M) caused a significant inhibition of spontaneous and of acetylcholine-induced release of CA. In a K+-free medium ouabain (10(-10) M) had no effect on CA release. DPH (10(-5) M) and a low concentration of ouabain (10(-10) M) caused a significant activation of (Na + K)-ATPase in a membrane fraction of the adrenal medulla. It is suggested that DPH and low ouabain concentrations inhibit CA release from the adrenal by activation of the sodium pump. The possible mechanism involved is discussed.
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PMID:Mechanism of inhibition of catecholamine release from adrenal medulla by diphenylhydantoin and by low concentration of ouabain (10(-10) M). 13 99

Post-tetanic potentiation (PTP) of monosynaptic reflex was estimated in spinal cords in the drug-free state after the administration of a convulsant dose of penicillin and after the administration of phenytoin. There was no apparent correlation between the degree of depression of PTP and the efficacy of controlling seizure activity by phenytoin. Extracellular potassium levels were measured with ion-selective microelectrodes. The post-stimulation clearing of [K+]0 was not accelerated by phenytoin, and frequently it was slowed. Post-stimulus undershooting of [K+]0 was diminished. Oxidation of NADH in cortex and of cytochrome a, a3 in spinal cord were measured by optical methods. Stimulus-evoked transient oxidation responses evoked by electrical stimulation were depressed by phenytoin. It is concluded that systemic administration of phenytoin in therapeutic doses does not stimulate Na+-K+-activated membrane ATPase in cortex and spinal cord. Unlike other depressants, phenytoin did not cause a reduction of "resting" redox levels of respiratory enzymes. The local regulation of blood flow remained unaltered after phenytoin administration. Phenytoin caused a moderate but consistent depression of the stimulus-evoked responses of potassium activity, electric potential, and oxidative enzymes, consistent with diminished outflow of potassium from cells, owing either to lesser activation of cells or to a lesser exchange of ions.
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PMID:Phenytoin, electric, ionic, and metabolic responses in cortex and spinal cord. 19 41

Phenytoin stimulated renin secretion from rat renal cortical slices. A sigmoid relationship was found between stimulatory effect and log concentration, from 1 to 8 mg/100 ml. The ED5C was 2.8 mg/100 ml. Basal secretion and the stimulation of secretion elicited by phenytoin were blocked by incubating slices in a K-free medium and by adding 1 mM ouabain to the medium (both of which inhibit Na,K-adenosine triphosphatase activity and increase intracellular Na concentration), and by reductions in the Na concentration of the incubation medium. NaCl in the incubation medium was replaced by choline chloride so that osmolality and Cl concentration were held constant. It is suggested that renin secretion rate is directly related to the transmembrane Na gradient, that phenytoin stimulates secretion by increasing the gradient, and that ouabain, K-free medium and reductions in Na concentration of the medium inhibit secretion by reducing the gradient.
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PMID:Phenytoin stimulates renin secretion from rat kidney slices. 51 21

Partially purified (Na+,K+)-ATPase (E.C. 3.6.1.3.) was investigated in the epileptic cortex of audiogenic DBA/2 mice and in the primary and secondary foci of cats with acute or chronic freeze lesions. No differences in specific activities measured at 3 mM K+ were observed between epileptic and control cortex, except an increase of enzymic activities in the primary focus of acutely lesioned cats. The (Na+,K+)-ATPase catalytic subunits were resolved by SDS-gel electrophoresis and their phosphorylation levels were measured in presence of K+ ions and phenytoin. K+ was more effective in inducing maximal dephosphorylation of (Na+,K+)-ATPase in C57/BL, with identical affinity in the two strains. Phenytoin decreased the net phosphorylation level of (Na+,K+)-ATPase by about 50% in C57/BL mice, but only by 20% in DBA/2 mice. Both K+ and phenytoin dephosphorylating influences were decreased in primary and secondary foci of acutely lesioned cats. Those changes were limited to the alpha(-) subunit. In chronic cats, the dephosphorylating step of the (Na+,K+)-ATPase catalytic subunit recovered a normal affinity to K+, but its sensitivity to phenytoin remained decreased. Those differences in K+ and phenytoin influences on brain (Na+,K+)-ATPases between control and epileptic cortex might be responsible for the ictal transformation and seizure spread. In cats, the alteration of the alpha(-) isoform could mainly affect the glial cells.
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PMID:Phosphorylation of brain (Na+,K+)-ATPase alpha catalytic subunits in normal and epileptic cerebral cortex: I. The audiogenic mice and the cat with a freeze lesion. 165 58

A plasma membrane-rich fraction has been separated from liver cells and cells of two solid rat tumors. D23 hepatoma and MC7 sarcoma. On the basis of marker enzyme activity the membranes separating at the 31-41% interface on the discontinuous sucrose gradient were enriched 15- to 19-fold. No significant differences in the phospholipid (PL) composition of the three membrane fractions were observed. The PL fatty acid (FA) composition showed that the percentage of unsaturated FA in all three membranes was between 43 and 48%. However, the oleic acid:PUFA ratio was much greater from tumor membranes. Membrane cholesterol was also significantly lower for cells from both tumors compared with liver cells. The DPH fluorescence polarization of the membrane fractions showed that the membranes from cells of both tumors are significantly less ordered than those of liver at all temperatures measured (4-50 degrees C). The Mg2+ ATPase activity of the plasma membranes is inactivated by hyperthermia treatments. The enzyme from liver cells was more thermostable (LT50 = 53.86 degrees C) than that from cells of either D23 (LT50 = 47.51 degrees C) or MC7 (LT50 = 46.34 degrees C) tumors.
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PMID:Lipid composition of the membranes from cells of two rat tumors and its relationship to tumor thermosensitivity. 198

Cat soleus motor nerve terminals, after high frequency conditioning, generate a post-tetanic repetition (PTR) which leads to a post-tetanic (PTP) of the muscle response. This property enables quantitative assessment of enhancement or depression of this nerve terminal excitability in vivo. The present study focuses on ionic mechanisms underlying the PTRs produced in this neuromuscular system either by high frequency stimulation or edrophonium. Ouabain was used as a specific probe for inhibition of Na(+)-K+ ATPase and its known consequences on Na+ and Ca2+ translocation. Ouabain pretreatment doubled the duration over which single stimuli, following either high frequency or edrophonium conditioning produced PTR. Ouabain in the doses used had no effect per se but as a function of dose augmented the frequency dependent responses. This pointed to Na+ loading of nerve terminals via high frequency stimulation plus ouabain inhibition of Na(+)-K+ ATPase. Ouabain potentiation of PTR responses evidently depends on exchange of intra-terminal sodium for external calcium. Thus, calcium entry blockers, Mn2+, and Co2+ suppressed or abolished the potentiations both before and after ouabain. Diphenylhydantoin, a Na+ and Ca2+ blocker, acted similarly. The effects of stimulation frequency, ouabain and the sequence of events leading to PTR in the soleus neuromuscular system appeared in general no different from those derived from the many in vitro microphysiologic studies of this phenomenon. Thus, EPPs were augmented and prolonged. It was concluded that intracellular Ca2+ is critical for regulating the stability of systems in which repetitive firing is both a normal and abnormal function.
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PMID:The interactions of ouabain with post-tetanic and facilitatory drug potentiations at cat soleus neuromuscular junctions in vivo. 216 59

Ischemia gives rise to severe energy depletion and imbalance of Ca2+ homeostasis. This condition leads to activation of phospholipases A2, A1 and to attenuation of ATP dependent reacylation. As a result, free fatty acid (FFA) especially arachidonic acid accumulates. Phenytoin has been reported to blockade the various Ca2+ channels. In this study, we could investigate the effect of phenytoin on the liberation of FFA, energy metabolites, various nucleotides metabolism, Na+, K+-ATPase activity, and water and electrolyte contents in the ischemic brain. Inhibitory effects of phenytoin against FFA accumulation in the ischemia, and increase of parietal cortex water content in the recirculation were brought about. In addition, Na+,K+-ATPase activity in the ischemia was accelerated by phenytoin. Phenytoin may reduce intracellular Ca2+ by blocking the Ca2+ channel into the cytoplasma, or by activation of Na+-Ca2+ exchange transport system following the acceleration of Na+,K+-ATPase activity. Another conceivable way for this acceleration of Na+,K+-ATPase may be derived from the preservation of the energy state, protein metabolism, and lipid metabolism.
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PMID:[A study on the protective mechanism of phenytoin in transient global ischemia]. 255 Aug 30

Phenytoin, a potent antiepileptic drug, has been thought to stimulate Na+, K+ transport across cell membranes, but its influence on (Na+, K+)-ATPase activity remains highly controversial. We have investigated the effects of the drug on the phosphorylation level of (Na+, K+)-ATPase partially purified from mouse, cat and human brain. (Na+, K+)-ATPase catalytic subunits [alpha(+) and alpha(-)] were resolved by sodium dodecylsulfate polyacrylamide gel electrophoresis. Previous experiments had shown that phenytoin dephosphorylates the (Na+, K+)-ATPase catalytic subunit by +/- 50% in C57/BL mice. In the present study, we showed that phenytoin (10(-4) M) decreases the phosphorylation level of (Na+, K+)-ATPase catalytic subunit by the same value in cat and human cortex. Moreover, that effect is predominant on the alpha(-) subunit, thought to be the predominant enzymatic form in non-neuronal or glial cells. The results are thus favoring the hypothesis that phenytoin stimulates the brain (Na+, K+)-ATPase. They further suggest that phenytoin mainly activates the glial enzymatic form, providing central nervous system with an enhanced ability to regulate extracellular K+.
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PMID:Phenytoin dephosphorylates the alpha(-) catalytic subunit of (Na+, K+)-ATPase. A study in mouse, cat and human brain. 255 36

The effect of magnesium on the phospholipid order parameter and not the conformation of purified pig kidney outer medulla (Na+ + K+)-ATPase was investigated by fluorescence techniques. Measurements with a fluorescent probe TMA-DPH and its sensitized fluorescence with tryptophan residues as donors revealed that magnesium increased the order of the membrane phospholipids both in the lipid annulus and in the bulk phase. Changes in the lipid order induced by Mg2+ can be closely referred to the protein arrangement followed by the steady-state anisotropy of FITC-labeled (Na+ + K+)-ATPase.
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PMID:Mg2+-induced changes of lipid order and conformation of (Na+ + K+)-ATPase. 282 84

(Na+, K+)-ATPase (E.C.3.6.1.3) was partially purified from the cerebral cortex of audiogenic DBA/2 mice, from the primary and secondary epileptogenic foci of cats with a freeze lesion and from normal and epileptic human cortices. No differences in the specific activities of the microsomal enzyme were observed between normal and epileptic cortex. The influence of K+ ions and phenytoin, a potent antiepileptic drug, was then studied on the phosphorylation level of (Na+, K+)-ATPase alpha(+) (neuronal) and alpha(-) (non-neuronal) catalytic subunits resolved by SDS-gel electrophoresis. In normal cortex, the apparent affinity of the non-neuronal enzyme to K+ ions was reduced compared to the affinity of the neuronal enzyme. Phenytoin decreased the phosphorylation level of (Na+, K+)-ATPase purified from non-epileptogenic cortex of control C57/BL mice, cats and human patients. In fact, the drug induced the dephosphorylation of the (Na+, K+)-ATPase catalytic subunits, mainly of its alpha(-), non-neuronal subtype. In the cortex of audiogenic DBA/2 mice, K+ ions induced the dephosphorylation of (Na+, K+)-ATPase, with the same affinity as in control C57/BL mice. The dephosphorylating influence of phenytoin was however much decreased. In the primary and secondary foci of lesioned cats, both K+ and phenytoin dephosphorylating influences were decreased. Those changes were especially valid for the alpha(-), non-neuronal subunit. In human epileptic cortex, the (Na+, K+)-ATPase catalytic subunit had a decreased affinity to K+, as well as it lost its sensitivity to phenytoin dephosphorylation. Those results confirm the existence of two molecular forms of (Na+, K+)-ATPase in animal and human brain cortex. Those two forms, the neuronal and the non-neuronal or glial (Na+, K+)-ATPases, differ at least by their K+ regulation and their phenytoin sensitivity. Phenytoin studies also suggest that the drug stimulates the cortical (Na+, K+)-ATPase, mainly its glial form, providing central nervous system with an enhanced ability to regulate extracellular K+. In epileptic cortex, (Na+, K+)-ATPase and especially its glial form is altered in its K+ regulation and phenytoin sensitivity. That deficiency of glial (Na+, K+)-ATPase in focal epileptogenic cortex could be responsible for ictal transformation and seizure spread (Acta neurol. belg., 1988, 88, 257-280).
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PMID:Brain cortical (Na+ K+)-ATPase in epilepsy. A biochemical study in animals and humans. 285 92


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