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

---

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

Alterations of tyrosine hydroxylase activity in various regions of brain from rats postnatally exposed to lead were tested. Three groups of animals were prepared; (1) Rats exposed to lead at a low dose (0.05% lead acetate, PbAc); (2) Rats exposed to lead at a high dose (0.2% PbAc); (3) Age-matched normal control rats. At 2, 4, 6, and 8 weeks of age, weight of brain and body, and concentrations of lead in whole brain of animals in each group were measured. Activities of tyrosine hydroxylase and Na(+)-K+ ATPase were also measured at the same ages in 4 brain regions of each animal. Body weight gain was decreased after 6 weeks of age in rats exposed to lead at a high dose. Concentrations of lead in whole brain were increased from 0.37 to 0.83 (ng/mg wet tissue) in these animals. Exposure of rats to lead generally increased tyrosine hydroxylase activity and decreased Na(+)-K+ ATPase activity. However, changes of tyrosine hydroxylase activity were detected without concomitant changes of Na(+)-K+ ATPase activity in pons-medulla at 2 weeks of age and telencephalon at 6 weeks of age in rats exposed to lead at a low dose, and in midbrain at 4 and 6 weeks of age in rats exposed to lead at a high dose. These data imply that catecholaminergic nervous system in the brain regions described above could be selectively affected by lead.
...
PMID:Selective effect of chronic lead ingestion on tyrosine hydroxylase activity in brain regions of rats. 136 52

Studies of various parameters of amino acid and catecholamine metabolism in human cerebral cortex have provided a number of biochemical markers that appear to delineate areas of focal epileptic activity. These observations have been consolidated further by investigations of a number of experimental models of epilepsy in animals. In appraising this data, it is important to take into consideration whether the tissue samples were obtained during an actual seizure state or in an interictal period. It is also important when possible to assess the extent of astrogliosis and neuronal loss. Sites of spontaneously active epileptic spiking in the cerebral neocortex have a somewhat different amino acid profile when compared to gray matter obtained from surrounding nonspiking gyri several centimeters away. There is an elevation in glycine content, a relative diminution in taurine, and a trend towards lowered glutamic acid levels. However, the concentrations of the eight amino acids measured appear in both the foci and surround to still be within the general range for normal tissue. Measurements of key enzymes involved in the synthesis and regulation of neurotransmitters provide a complementary method of evaluating functional changes in epileptic brain as they are generally less labile than their substrates. There is a moderate increase in the activity of glutamic acid dehydrogenase, an enzyme that plays an important role in the synthesis of glutamic acid from glucose. In some patients a decrease in glutamic acid decarboxylase has also been reported: this enzyme forms gamma-aminobutyric acid (GABA) from glutamic acid and is thus important for inhibition in the central nervous system. Moreover, there is a striking increase in the activity of tyrosine hydroxylase, the rate-limiting enzyme responsible for catecholamine synthesis. The possibility of a focal abnormality in catecholamine metabolism is reinforced by the simultaneous finding of a relative decrease in the number of alpha-1 postsynaptic receptor sites. An important marker of energy metabolism in neural tissue, Na+,K+-ATPase activity, has also been found to be decreased in actively spiking human cerebral cortex. Data from experimental animal foci produced by topical application of convulsant agents show a consistent drop in glutamic acid tissue content. This can be matched to an efflux of glutamic acid from the cortical surface, which in turn is proportional to the electrographic activity of the spike focus. In addition, there is often also a decrease in taurine and GABA in such foci, as well as an increase in the levels of a number of neutral amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Amino acid and catecholamine markers of metabolic abnormalities in human focal epilepsy. 287 18

Abnormalities in the function of the central nervous system exist in phosphate depletion (PD). It is possible that this is due to an adverse effect of PD on the metabolism of neurotransmitters, such as norepinephrine (NE), in brain synaptosomes. We examined the effects of PD, produced by restriction of dietary phosphate intake on NE metabolism of brain synaptosomes. Synaptosomes from PD rats had significantly reduced NE content, uptake and release, elevated Km, but normal Vmax of tyrosine hydroxylase, normal Km and Vmax of monoamine oxidase, elevated resting levels of cytosolic calcium ([Ca2+]i), higher delta [Ca2+]i in response to KCl, higher delta [Ca2+]i/basal [Ca2+]i ratio, lower ATP content and reduced activity of Na(+)-K(+)-ATPase as compared to synaptosomes from pair-weighed rats. Treatment of PD rats with verapamil corrected all the synaptosomal derangements except for the elevated Km of tyrosine hydroxylase and NE content. Verapamil did not affect the metabolism of PW rats. The data demonstrate that PD causes significant derangements in NE metabolism of brain synaptosomes. Observations in the present study and in others indicate that these derangements in NE metabolism are due to the PD-induced abnormalities in the homeostasis of synaptosomal [Ca2+]i, ATP and phospholipids and in the activities of Na(+)-K(+)-ATPase and Ca(2+)-ATPase.
...
PMID:Abnormal norepinephrine metabolism in rat brain synaptosomes in phosphate depletion. 810 Jun 85

The relationship between elevations in intracellular free Ca2+ concentration ([Ca2+]i) by different mechanisms and tyrosine hydroxylase (TH) gene expression was examined. Depolarization by an elevated K+ concentration triggered rapid and sustained increases in [Ca2+]i from a basal level of approximately 50 to 110-150 nM and three- to fourfold elevations in TH mRNA levels, requiring extracellular calcium but not inositol 1,4,5-trisphosphate (IP3). On the other hand, bradykinin or thapsigargin, both of which induce release of intracellular calcium stores via IP3 or inhibition of Ca(2+)-ATPase, rapidly elevated [Ca2+]i to > 200 nM and increased TH gene expression (three-to fivefold). Confocal imaging showed that the elevations in [Ca2+]i in each case occurred throughout the cyto-and nucleoplasm. The initial rise in [Ca2+]i due to either bradykinin or thapsigargin, which did not require extracellular calcium, was sufficient to initiate the events leading to increased TH expression. Consistent with this, the effects of bradykinin on TH expression were inhibited by 1, 2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid or 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester which chelates or inhibits the release of intracellular calcium, respectively. Bradykinin required a rise in [Ca2+]i for < 10 min, as opposed to 10-30 min for depolarization to increase TH mRNA levels. These results demonstrate that although each of these treatments increased TH gene expression by raising [Ca2+]i, there are important differences among them in terms of the magnitude of elevated [Ca2+]i, requirements for extracellular calcium or release of intracellular calcium stores, and duration of elevated [Ca2+]i, indicating the involvement of different calcium signalling pathways leading to regulation of TH gene expression.
...
PMID:Involvement of intracellular or extracellular calcium in activation of tyrosine hydroxylase gene expression in PC12 cells. 893 63

1. Carnosine, anserine, and homocarnosine are endogenous dipeptides concentrated in brain and muscle whose biological functions remain in doubt. 2. We have tested the hypothesis that these compounds function as endogenous protective substances against molecular and cellular damage from free radicals, using two isolated enzyme systems and two models of ischemic brain injury. Carnosine and homocarnosine are both effective in activating brain Na, K-ATPase measured under optimal conditions and in reducing the loss of its activity caused by incubation with hydrogen peroxide. 3. In contrast, all three endogenous dipeptides cause a reduction in the activity of brain tyrosine hydroxylase, an enzyme activated by free radicals. In hippocampal brain slices subjected to ischemia, carnosine increased the time to loss of excitability. 4. In in vivo experiments on rats under experimental hypobaric hypoxia, carnosine increased the time to loss of ability to stand and breath and decreased the time to recovery. 5. These actions are explicable by effects of carnosine and related compounds which neutralize free radicals, particularly hydroxyl radicals. In all experiments the effective concentration of carnosine was comparable to or lower than those found in brain. These observations provide further support for the conclusion that protection against free radical damage is a major role of carnosine, anserine, and homocarnosine.
...
PMID:Biochemical and physiological evidence that carnosine is an endogenous neuroprotector against free radicals. 914 Jul 2

We examined the effect of intracerebroventricular (i.c.v.) administration of mu-opioid agonist, morphine, and its antagonist naloxone followed by morphine on the activities of monoamine-metabolizing enzymes, namely tyrosine hydroxylase (TH) and monoamine oxidase (MAO) along with adenosinetriphosphatase (Na+, K+ -ATPase), the enzyme responsible for the maintenance of ionic gradients across the membrane, in seven discrete regions of brain from estrogen- and progesterone-primed ovariectomized rats. TH activity decreased after morphine treatment in some areas such as the median eminence-arcuate region (ME-ARC), the amygdala, and the thalamus, showing statistically significant change. MAO activity increased in all the areas studied, but more appreciable change was observed in medial preoptic area (mPOA), the ME-ARC region, and the cortex. Pronounced increase in Na+, K+ -ATPase enzyme activity was observed after the drug treatment. Naloxone given prior to morphine injection resulted in recovery of the enzyme activities in most of the areas studied. Our study may provide insights into the precise opioidergic modulation of gonadotropin releasing hormone (GnRH) release mechanisms through the involvement of monoaminergic system, elucidating the basis of various neuronal dysfunctions and their management in opioid addicts.
...
PMID:Role of opioidergic and monoaminergic neurotransmission in the GnRH release mechanism of EBP-primed OVX rats. 976 93

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide first isolated from ovine hypothalamic tissue. This peptide stimulates adenylate cyclase activation. However, few details were known of the function of this peptide on stimulus-secretion coupling in neuronal cells. The authors have investigated the role of PACAP on catecholamine biosynthesis and secretion using cultured bovine adrenal chromaffin cells as a model for catecholamine-containing neurons. PACAP38, the 38-amino acid form of PACAP, increased cAMP formation in bovine adrenal chromaffin cells. In addition, PACAP38 increased [Ca2+]i associated with PI turnover and Ca2+ influx into the cells. The synthesis of catecholamine and the phosphorylation of tyrosine hydroxylase, a rate-limiting enzyme of catecholamine biosynthesis, stimulated by the maximal effective concentration of dibutyryl cAMP or a high concentration (56 mM) of K+ were further enhanced by PACAP38. Thus PACAP38 stimulated the pathway of catecholamine biosynthesis mainly by both activation of cAMP- and Ca2(+)-dependent protein kinases. On catecholamine secretion from the cells, the effect of PACAP38 was markedly potentiated by addition of ouabain, an inhibitor of Na+/K+ ATPase. This markedly potentiated secretion was greatly reduced with Na+ omitted-sucrose medium. PACAP38 increased 22Na+ influx into the cells treated with ouabain. Thus PACAP38 with ouabain stimulated catecholamine secretion by accumulation of intracellular Na+, resulting in an increase in Ca2+ influx. These results indicate that the neuropeptide PACAP has an important role in stimulus-secretion coupling in adrenal chromaffin cells.
...
PMID:[Possible role of a neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) on stimulus-secretion coupling in catecholamine neuron]. 1223 56

The aim of this study was to investigate the effects of selegiline ((-)deprenyl), an irreversible inhibitor of monoaminoxidase-B (MAO-B): (a) on brain acetylcholinesterase (AChE), (Na(+),K(+))-ATPase and Mg(2+)-ATPase activities; (b) total antioxidant status (TAS); (c) learning performance and to evaluate possible correlation between biochemical and behavioral findings after long-term drug administration in aged male rats. Selegiline (0.25mgkg(-1) rat) was administered once every other day for 50 days. Learning parameters were tested through a two-way active avoidance procedure taking place in an Ugo-Basile automated shuttle box device. Enzyme activities and TAS were evaluated spectrophotometrically in brain homogenates of decapitated animals. TAS was significantly lower in aged compared to adult rats and this was reversed by selegiline administration. The decrease of free radical production by selegiline resulted in the stimulation of AChE and (Na(+),K(+))-ATPase. Mg(2+)-ATPase activity was not affected by the drug. Selegiline seems to improve the avoidance performance as compared to control groups. It is concluded that: (a) MAO-B inhibition and/or free radical protection on tyrosine hydroxylase by the drug may increase brain catecholamine concentrations resulting possibly in (Na(+),K(+))-ATPase stimulation; (b) AChE and (Na(+),K(+))-ATPase activation by the drug could modulate brain cholinergic, catecholaminergic and serotoninergic systems as well as the neural excitability and metabolic energy production; and (c) selegiline seems to improve the learning performance of aged rats.
...
PMID:Selegiline long-term effects on brain acetylcholinesterase, (Na+,K+)-ATPase activities, antioxidant status and learning performance of aged rats. 1286 Apr 42

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.
...
PMID:Demonstration of functional coupling between dopamine synthesis and its packaging into synaptic vesicles. 1463 Nov 17

Rat brain synaptic vesicles were isoosmotically isolated and examined for Mg(2+)-ATPase [EC 3.6.1.3.] and tyrosine hydroxylase [EC 1.14.16.2.] associated with the synaptic vesicles. Synaptosomes in 0.32 M sucrose were disrupted by freezing and thawing treatment, and the cytosol fraction was fractionated on a Sephacryl S-500 column with a mean exclusion size of 200 nm. Peak I at the void volume was a mixture of large vesicular membranes, small amounts of synaptic vesicles and coated vesicles, etc. Peak II consisted of non- and granulated synaptic vesicles of 35-40 nm diameter, and peak III of soluble proteins. The synaptic vesicles in peak II reacted with antibodies against the H(+)-ATPase A-subunit, vesicular acetylcholine transporter, and vesicular monoamine transporter. However, they showed little Mg(2+)-ATPase activity. Tyrosine hydroxylase was observed in either peak II or III on blotting with an anti-tyrosine hydroxylase antibody. These results imply that tyrosine hydroxylase exists in soluble and bound forms to synaptic vesicles in nerve terminals.
...
PMID:Isoosmotic isolation of rat brain synaptic vesicles, some of which contain tyrosine hydroxylase. 1549 95


1 2 3 Next >>

---