Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Programmed-feeding polydipsia results in a reliable model of chronic alcoholism in the rat. High oral ethanol comsumption and a predictable withdrawal reaction associated with audiogenic seizures are produced. The maintenance of high blood ethanol levels for three weeks in 18 male Charles River rats was associated with audiogenic seizures after 6 or 8 hours of withdrawal. These chronic alcoholic rats had enhanced blood clearance of ethanol. The cerebral cortical crude mitochondrial fraction showed a decrease in total and magnesium-dependent adenosine triphosphatase activity in alcoholic and control (water-fed) rats compared with normal rats.
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PMID:Programmed feeding as a model of chronic alcoholism in the rat. 15 1

Intact nerve endings (synaptosomes) have been isolated from spiking and non-spiking temporal cortex and hippocampus samples from 14 patients immediately after temporal lobectomy for intractable epilepsy. Synaptosomes were also prepared from frozen brain samples of humans with no known neurological diseases. Four adenosine triphosphatase (ATP)-metabolizing enzymes (ecto-ATPase, ecto-adenylate kinase, Na+,K(+)-ATPase and Ca2+,Mg2(+)-ATPase) were assayed in the synaptosomal fractions from the most spiking temporal cortex area (including focus) as well as from various regions of the hippocampus, and compared with enzyme activities of the least spiking or non-spiking temporal cortex of the same patient. Enzyme activities of the epileptic brain samples were also compared with values measured in the corresponding regions of normal brains. Ecto-ATPase activities of epileptic temporal cortex were decreased (approximately 30%) in both comparisons. In contrast to these findings, a substantially increased (in some cases 300%) ecto-ATPase activity was observed in the posterior part of epileptic hippocampus. We suggest that the higher than normal ecto-ATPase activity in this particular hippocampal region is related to the presence of granule cells and their efferent (or afferent) synaptic connections. The synaptosomal ecto-adenylate kinase showed alterations opposite to the changes found for the ecto-ATPase. The intrasynaptosomal ATPase (Na+,K(+)- and Ca2+,Mg2(+)-) were decreased in the epileptic hippocampus-, but not in the temporal cortex samples, in relation to the corresponding normal enzyme activity values. These complex alterations in synaptosomal ATP-metabolizing enzyme activities may be important elements of seizure development and maintenance in human temporal lobe epilepsy.
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PMID:Synaptosomal ATPase activities in temporal cortex and hippocampal formation of humans with focal epilepsy. 217 27

Previous studies have demonstrated that electrically induced seizures in rat result in an increased brain intracellular sodium which can be decreased by treatment with sodium diphenylhydantoin (DPH). The correlation of cation transport with membrane-oriented sodium-potassium-adenosine triphosphatase (Na-K-ATPase) prompted an investigation of the effect of DPH upon ATPase enzyme activity.Rat cerebral cortical synaptosomes isolated in Ficoll gradients were employed as the source for Na-K-ATPase. With 50 mM Na, 10 mM K, 7.5 mM Mg, and 1.8 mM ATP, the specific activity of the preparation was 70 mumoles P(i) released/mg synaptosomal protein per 30 min. The ionic and substrate concentrations yielding one-half maximal velocity were 0.5 mM K, 5 mM Na, and 8.5 x 10(-5) M ATP, respectively. At 50 mM Na and 0.2 mM K, DPH produced an average of 92% stimulation of P(i) release above control. The ratio of Na:K rather than the absolute levels of the ions was critical in determining the effect of DPH. DPH produced significant stimulation of enzyme activity under conditions of a high Na:K ratio (25-50:1). At ratios of 5-10:1, DPH produced little or no effect, and at low Na:K ratios (less than 5:1), DPH was inhibitory. Under all ionic conditions examined, DPH produced no apparent change in enzyme affinity for ATP. Assuming the proposed association of Na-K-ATPase with cation transport in brain, the data suggest the possibility that DPH may control seizures by its stimulation of Na-K-ATPase activity.
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PMID:Effect of diphenylhydantoin on synaptosome sodium-potassium-ATPase. 423 89

Much evidence shows that glia regulates the cation and anion content of brain interstitial space. In rats the pH and bicarbonate (HCO3-) concentration of neurons and glia were derived from carbon 14-labeled HCO3- and dimethyloxazolidinedione uptake into brain and cerebrospinal fluid. Acetazolamide increases the total CO2 concentration in neurons and decreases the pH and HCO3- concentration in glia. Inhibition of glial carbonic anhydrase (CA) reduces conversion of neuronally derived CO2 to HCO3-, glial pH is lowered, and neuronal CO2 accumulates. CA therefore has an essential role in regulating pH in neurons, glia, and interstitial fluid. In audiogenic seizure mice, glial CA activity is increased and glial anion transport is reduced. As the mice age, seizure susceptibility, the increased CA activity, and the defect in anion transport disappear concurrently. The enhanced CA activity in the glial cells of these mice is an adaptive mechanism to overcome the defect in anion transport that results from a deficiency of HCO3- -dependent and Na+- and K+ -dependent adenosine triphosphatase. Pentylenetetrazol stimulates neurons in neonatal rats, but after 10 days of age, when glia is present, it too is stimulated and the seizures are attenuated. Cobalt implantation in the cortex of rats also induces a glial response that ameliorates the focal seizures produced by this procedure.
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PMID:Ionic and acid-base regulation of neurons and glia during seizures. 615 Jun 82

Marked asterixis occurred in two patients following metrizamide myelography. One also suffered generalized seizures and the other had severe stuttering speech for seven days. The spectrum of toxic manifestations of metrizamide is reviewed with emphasis on the unusual lethargy and other depressive effects seen with this relatively safe agent. The hypothesis that metrizamide exerts a ouabain-like effect on the cortical surface was tested. Metrizamide in concentrations as high as 20 mM had no inhibitory effect on rat cerebral K+-para-nitrophenylphosphatase, a partial reaction of (Na+K+)-adenosine triphosphatase. Because metrizamide is a 2-deoxyglucose analogue, a competitive inhibition of hexokinase at the first step in glycolysis was also postulated. Metrizamide was found to competitively inhibit commercial (microbial) hexokinase. The Michaelis constant for glucose rises from 0.13 to 0.25 to 0.33 to 0.91 mM in the presence of 0, 0.4, 1.0, and 2.0 mM metrizamide, respectively. Since the concentration of metrizamide over the cerebral cortex after routine myelography may be approximately 50 mM compared with a glucose concentration of only 3.6 mM (65 mg/dl), it is postulated that impaired brain glucose metabolism may be responsible for some of the toxic effects of metrizamide.
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PMID:Asterixis and encephalopathy following metrizamide myelography: investigations into possible mechanisms and review of the literature. 722 1

Neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome and maternally inherited Leigh's syndrome have been associated with T8993G point mutations in the mitochondrial adenosine triphosphatase 6 gene. Typically, NARP syndrome is characterized by developmental delay, seizures, dementia, retinitis pigmentosa, ataxia, sensory neuropathy, and proximal weakness. Usually, there is a correlation between the percentage of mutated mitochondrial DNA and clinical severity, and when mutated mitochondrial DNA is > 90%, it is often seen with Leigh's syndrome. We now report a family with mitochondrial DNA T8993G mutation in eight living members, five with mutant mitochondrial DNA >90% and one with 20% mutant mitochondrial DNA. However, their clinical features include variable combinations of seizures, behavior problems, learning disability, mental retardation, sensorineural deafness, cerebellar ataxia, and proximal muscle weakness. No retinitis pigmentosa was found in all eight living members, including a 56-year-old grandmother. Only one dead female relative was diagnosed with Leigh's syndrome on the neuropathologic examination at age 22 years, when she died of an accident. High mitochondrial DNA T8993G mutation is not always associated with typical features of Leigh's and NARP syndromes.
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PMID:High mitochondrial DNA T8993G mutation (<90%) without typical features of Leigh's and NARP syndromes. 1145 54

Mitochondrial disorders associated with defects in the respiratory chain can be attributable to mutations in the mitochondrial genome (mitochondrial DNA) or the nuclear genome (nuclear DNA). Because the brain is highly dependent on oxidative metabolism, encephalopathy is a common presentation, and epilepsy is a clinical hallmark of many of these conditions. Although most mutations in mitochondrial DNA do not present in infancy, a few mutations in the adenosine triphosphatase gene cause maternally inherited Leigh disease and infantile epilepsy. Early-onset epilepsy is more commonly associated with defects of nuclear genes encoding subunits of respiratory chain complexes or proteins needed for the correct assembly and functioning of the complexes. These defects generally cause autosomal recessive Leigh disease. In this review, the frequency and types of epilepsy (particularly early-onset seizures) are compared according to a genetic classification of the mitochondrial disorders.
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PMID:Mitochondrial disorders. 1259 54

Mitochondrial DNA defects were known to be associated with a wide spectrum of human diseases and patients might present a wide range of clinical features in various combinations. In the current study, we described a patient with psychomotor and neurodevelopmental delay, mild hyperintensity of posterior periventicular white matter, generalized clonic seizures, leukodystrophy, and congenital deafness. He also had tetraplegia, with central blindness and swallowing difficulty. Brain magnetic resonance imaging (MRI) showed involvement of the interpeduncular nucleus and central tegmental tract, white matter abnormalities, and cerebellar atrophy. A whole mitochondrial genome screening revealed the presence of 19 reported polymorphisms and an undescribed A to G mutation at nucleotide 8411 (p.M16V) affecting a conserved region of the mitochondrial adenosine triphosphatase (ATPase) 8 protein. This de novo mutation was detected in heteroplasmic form (97%) and was absent in 120 controls. Thus, the m.8411A>G mutation could strongly be associated with the disease in the tested patient.
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PMID:A de novo mutation in the adenosine triphosphatase (ATPase) 8 gene in a patient with mitochondrial disorder. 2020 8