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)

Regulation of intracellular Ca2+ homeostasis was characterized in epimastigote forms of Trypanosoma cruzi using the fluorescence probe Fura-2. Despite an increase in extracellular Ca2+, [Ca2+]o, from 0 to 2 mM, cytosolic Ca2+, [Ca2+]i, increased only from 85 +/- 9 to 185 +/- 21 nM, indicating the presence of highly efficient mechanisms for maintaining [Ca2+]i. Exposure to monovalent Na+ (monensin)-, K+ (valinomycin, nigericin)-, and divalent Ca2+ (ionomycin)-specific ionophores, uncouplers of mitochondrial respiration (oligomycin), inhibitors of Na+/K(+)-ATPase (ouabain), and Ca(2+)-sensitive ATPase (orthovanadate) in 0 or 1 mM [Ca2+]o resulted in perturbations of [Ca2+]i, the patterns of which suggested both sequestration and extrusion mechanisms. Following equilibration in 1 mM [Ca2+]o, incubation with orthovanadate markedly increased [Ca2+]i, results which are compatible with an active uptake of [Ca2+]i by endoplasmic reticulum. In contrast, equilibration in 0 or 1 mM [Ca2+]o did not influence the relatively smaller increase in [Ca2+]i following incubation with oligomycin, suggesting a minor role for the mitochondrial compartment. In cells previously equilibrated in 1 mM [Ca2+]o, exposure to monensin or ouabain, conditions known to decrease the [Na+]o/[Na+]i gradient, upon which the Na+/Ca2+ exchange pathways are dependent, markedly increased [Ca2+]i. In a complementary manner, decreasing the extracellular Na+ gradient with Li+ increased [Ca2+]i in a dose-dependent manner. Finally, the calcium channel blockers verapamil and isradipine inhibited the uptake of Ca2+ by greater than 50%, whereas diltiazem, nifedipine, and nicardipine were ineffective. The results suggest that epimastigote forms of T. cruzi maintain [Ca2+]i by uptake, sequestration, and extrusion mechanisms, with properties common to eukaryotic organisms.
...
PMID:Trypanosoma cruzi: mechanisms of intracellular calcium homeostasis. 131 97

The activity of Na(+)-K+ ATPase of pancreatic islets modulates their insulin secretion. The study presented here examined the activity of this enzyme in pancreatic islets of chronic renal failure (CRF) rats in an effort to further delineate the mechanisms of impaired insulin secretion in CRF. The Vmax of Na(+)-K+ ATPase, but not its Km, and the ATP content are significantly reduced in islets of CRF rats that have elevated levels of parathyroid hormone (PTH). These derangements are prevented by prior parathyroidectomy of CRF rats (low blood levels of PTH) or by their treatment with the calcium channel blocker verapamil; these latter rats have sustained elevation of blood levels of PTH. The data indicate that the chronic excess blood levels of PTH in CRF initiates events (augmented entry of calcium) that lead to the reduction in ATP content and in Vmax of Na(+)-K+ ATPase of pancreatic islets. Reducing the blood levels of PTH by parathyroidectomy or blocking the action of PTH on calcium entry into cells by verapamil prevents these derangements. The results suggest that chronic inhibition of Na(+)-K+ ATPase may participate in the processes underlying the impaired insulin secretion in CRF.
...
PMID:Reduced activity of Na(+)-K+ ATPase of pancreatic islets in chronic renal failure: role of secondary hyperparathyroidism. 132 Sep 48

Spermatozoal plasma membrane vesicles isolated from distal portion of the epididymis and vas deferens were found to contain Ca(++)-activated ATPase and calcium transport activities. Nifedipine was administered at two different doses (1.0 and 2.5 mg/kg b.w./day) and the effect was observed for both short- (4 week) and long-term (12 week) period. The cellular ionic calcium content and Ca(++)-ATPase activity were observed to be enhanced in the drug-treated animals. The recovery studies carried out after 4 and 6 weeks of withdrawal of the drug treatment exhibited partial to complete restoration of observed changes. The stimulatory rather than inhibitory effect of Nifedipine, a specific calcium channel blocker, on calcium uptake may suggest that voltage-sensitive calcium channels may be lacking in guinea pig spermatozoa. The stimulatory effect of the drug is speculated to be either by inhibition of Na(+)-Ca++ antiporter or G-protein activated agonistic effect or probably due to altered physicochemical properties of the drug-treated sperm plasma membranes.
...
PMID:Calcium transport and Ca(++)-ATPase activity in spermatozoal plasma membrane vesicles of nifedipine-administered guinea pigs. 132 36

Since cellular calcium transport mechanisms during biological calcification are less known, a series of experiments were performed by in vivo as well as in vitro methodologies in the dentinogenically active rat incisor. By means of micro-electrode technique, the pH and pCa (calcium ion activity) in predentin in situ were found to be 7.0 and 2.9, respectively. It was concluded that there exists a Ca2+ion concentrating mechanism over the odontoblast layer in direction towards the mineralization front. The kinetics of this calcium flow was determined in vivo by radiotracer technique. The time for 45Ca2+ uptake into the dentin mineral phase was determined to 10-15 min. Transmembraneous Ca2+ ion pumps and channels in odontoblasts were further analyzed. The resting membrane potential of rat incisor odontoblasts was determined to -24 mV. Using ion-specific mini-electrode technique as well as fluorescence spectrophotometry, calcium channels, Ca(2+)-ATPase and Na+/Ca2+ antiports, responsible for cellular Ca2+ uptake and extrusion, were identified in the odontoblast plasma membrane. Dissected odontoblasts were subjected to subcellular fractionation. An electrophoretic uniporter and a Na2+/Ca2+ exchanger, for Ca2+ release and uptake, respectively, were demonstrated in mitochondria, whereas a Ca(2+)-ATPase was present in the microsomal fraction. Mitochondria, microsomes and whole, digitonin-permeabilized odontoblasts, were able to maintain a steady state Ca2+ activity at pCa = 6.4-6.6 in vitro. In rats treated with colchicine, the incorporation of 45Ca2+ into dentin mineral was severely altered. Similarly, administration to rats of specific calcium channel blockers strongly inhibited 45Ca2+ incorporation. Together, the results indicate that a transcellular pathway is a major route for Ca2+ ion transport during dentinogenesis, and that this may be under a relatively strict cellular control.
...
PMID:Calcium transport in dentinogenesis. An experimental study in the rat incisor odontoblast. 132 45

In agonist-stimulated clonal pituitary gonadotrophs (alpha T3-1 cells), cytoplasmic calcium ([Ca2+]i) exhibited rapid and prominent peak increases, followed by lower, but sustained, elevations for up to 15 min. The [Ca2+]i response to GnRH was rapidly inhibited by prior addition of a potent GnRH antagonist. In the absence of extracellular Ca2+ the initial peak [Ca2+]i response was only slightly decreased, but the prolonged increase in [Ca2+]i was abolished, indicating that the peak is derived largely from intracellular calcium mobilization and the sustained phase from Ca2+ influx. Application of the endoplasmic reticulum Ca(2+)-ATPase blocker thapsigargin caused progressive and dose-dependent elevation of [Ca2+]i and decreased the peak amplitude of the GnRH-induced Ca2+ response. On the other hand, addition of dihydropyridine calcium channel antagonists before or after GnRH treatment prevented or terminated the plateau phase, respectively, consistent with entry of Ca2+ through L-type voltage-sensitive Ca2+ channels (VSCC) as the major Ca2+ influx pathway during GnRH action. The presence of L-type VSCC in alpha T3-1 cells was further indicated by the ability of elevated extracellular K+ levels and the dihydropyridine calcium channel agonist Bay K 8644 to elevate [Ca2+]i in an extracellular calcium-dependent manner. These actions of depolarization and Bay K 8644 were inhibited by nifedipine, with an IC50 of 10 nM. High extracellular K(+)- and GnRH-induced Ca2+ entry was also attenuated by phorbol esters and permeant diacylglycerols, indicating that protein kinase-C exerts inhibitory modulation of VSCC activity. In contrast to normal pituitary gonadotrophs, in which GnRH induces a frequency-modulated oscillatory [Ca2+]i response, single alpha T3-1 cells exhibited a nonoscillatory amplitude-modulated signal during agonist stimulation. The [Ca2+]i responses observed in alpha T3-1 gonadotrophs indicate that the immortalized cells retain functional GnRH receptors and their coupling to the Ca2+ signaling pathway. Ca2+ influx through L-type channels maintains the plateau phase of the [Ca2+]i response during agonist stimulation and is inhibited by activation of protein kinase-C.
...
PMID:Gonadotropin-releasing hormone-induced calcium signaling in clonal pituitary gonadotrophs. 137 69

The mechanism of vitamin D-dependent intestinal calcium transport has been explored in experimental animals in vivo and in vitro with the aid of pharmacologic agents that inhibit steps in the translocation process. Glucocorticoids in vivo, but not in vitro, inhibit the mucosal-to-serosal flux (Jms) of calcium and thus reduce net calcium absorption. Chronic metabolic acidosis inhibits calcium transport in vivo through inhibition of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] production and by a direct effect in vitro on the enterocyte to decrease calcium Jms. Cellular functions that may be involved in the transport process have been inhibited in vitro, including brush border calcium uptake by calcium channel blockers; calmodulin-dependent Ca-activated ATPase by trifluoperazine; calcium binding to vitamin D-dependent calcium-binding protein (CaBP, calbindin) by theophylline and acidic lysosomal vesicle function by quinacrine, chloroquine and ammonium chloride. The results of these studies demonstrate the consequences of selectively inhibiting steps thought to be involved in calcium transport and suggest new directions for further research in elucidating mechanisms of cellular calcium transport.
...
PMID:The use of pharmacologic agents to study mechanisms of intestinal calcium transport. 154 31

Gentamicin and calcium compete for binding to various tissues including renal tubular brush border. Moreover, gentamicin has calcium channel blocking properties in cardiac and vascular tissue. Calcium channel blockade in vitro by nifedipine or verapamil decreases calcium uptake by renal tubular epithelial cells. To determine the acute in vivo effects of gentamicin on renal calcium handling, we administered gentamicin 10 mg/kg as an i.v. bolus to F344 rats. Within 30 min of administration fractional excretion of calcium increased from a mean of 11 +/- 2% (S.E.M.) to 128 +/- 37%. There was no change in glomerular filtration rate, or urinary sodium, potassium or phosphate excretion. Maximum calciuria occurred immediately after administration, was dose-related and was correlated to preadministration urinary calcium. Urine calcium concentration was also correlated to urinary gentamicin concentration. Urinary calcium returned to base-line values within 90 min of bolus gentamicin administration, but remained elevated if a gentamicin infusion was continued. Parathyroidectomy and dietary calcium content did not affect gentamicin calciuria. Tobramycin, a less nephrotoxic aminoglycoside in the F344 rat, had calciuric effects similar to gentamicin. Verapamil, a calcium channel blocker which is largely excluded from the urine, and potassium dichromate, a nonaminoglycoside proximal tubular nephrotoxin, had no effect on urinary calcium. The mechanism of aminoglycoside calciuria is unclear, but may be related to competition between aminoglycosides and calcium for brush border binding, intraluminal calcium channel blockade by aminoglycosides or aminoglycoside inhibition of basolateral calcium ATPase or Na-K ATPase.
...
PMID:Aminoglycoside-mediated calciuresis. 162 95

Vanadate alters intestinal transport and may have a role in regulating cell function. To determine whether it influences calcium absorption, we tested the effects of acute and chronic vanadate administration on calcium absorption using single-pass perfusion of jejunal and ileal segments of the in vivo rat intestine. Acute vanadate administration increased the lumen-to-mucosa and net fluxes of calcium in both the jejunum and ileum. The increase was largely due to an enhancement of the saturable fluxes of calcium and was observed at 10(-4) M concentration of vanadate, but not at higher or lower concentrations of the oxyanion, except at the highest concentration used, 10(-2) M, where calcium absorption was inhibited. Chronic vanadate administration caused, on the other hand, no changes in calcium absorption. We have demonstrated previously that rat intestinal (Na+ + K+)-ATPase is inhibited by vanadate, an effect that could raise cell sodium and increase the efflux of sodium across the brush border membrane. The results suggest that the vanadate enhancement of calcium absorption may be related to an increased entry of calcium into the mucosa, possibly as a result of an augmented exchange through the Na+/Ca+ antiport system. Alternatively, vanadate may influence access to a calcium channel in the mucosal membrane of the intestinal epithelium, leading to the observed increase in absorption.
...
PMID:Enhancement of rat intestinal calcium absorption by vanadate. 165 72

Lysophosphatidylcholine (LPC) accumulates in myocardial tissues during ischemia, and has toxic effects which may contribute to the arrhythmias and relaxation abnormalities that occur during acute ischemia. These effects of LPC may be mediated in part by calcium overload. To test this hypothesis, spontaneously contracting cultured embryonic chick ventricular myocytes were superfused with various concentrations of LPC (10, 50 and 100 microM) while effects on contractile motion (video motion detector) and changes in free intracellular calcium ion concentration ([Ca2+]i indo-1 fluorescence) were determined. At concentrations greater than or equal to 10 microM, a dose-related, time-dependent effect occurred after exposure to LPC, consisting of the development of contracture and marked elevation of [Ca2+]i. LPC also produced a dose-related, time-dependent inhibition of K+ uptake, indicating there was inhibition of the Na(+)-K+ ATPase Na+ pump. However, the LPC-induced increase in [Ca2+]i was not due to Na+ overload caused by inhibition of the Na(+)-K+ ATPase Na+ pump because superfusion with a zero-Na+ solution did not prevent an increase in [Ca2+]i after LPC exposure; and the increase in [Ca2+]i after exposure to LPC occurred too rapidly to be accounted for by Na+ pump inhibition. Removal of extracellular Ca2+ prevented the rise in [Ca2+]i, after exposure to LPC but treatment with verapamil failed to inhibit the increase in [Ca2+]i induced by LPC. We conclude that LPC produces contracture due to an increase [Ca2+]i. These effects are seen at concentrations of 10 microM and greater, are not due to altered Na(+)-K+ ATPase Na+ pump or calcium channel function, and are probably related to the detergent properties of this amphiphile. There effects may account in part for myocardial dysfunction during ischemia in intact tissue.
...
PMID:Lysophosphatidylcholine increases cytosolic calcium in ventricular myocytes by direct action on the sarcolemma. 165 42

Cardiovascular disease represents the major cause of morbidity and mortality in noninsulin-dependent diabetic patients. While it was once thought that atherosclerotic vascular disease was responsible for all of these adverse effects, recent studies support the notion that one of the major adverse complications of diabetes is the development of a diabetic cardiomyopathy characterized by defects in both diastolic and systolic function. Contributing to the development of the cardiomyopathy is a shift in myosin isozyme content in favor of the least active V3 form. Also defective in the noninsulin-dependent diabetic heart is regulation of calcium homeostasis. While transport of calcium by the sarcolemmal and sarcoplasmic reticular calcium pumps are minimally affected by noninsulin-dependent diabetes, significant impairment occurs in sarcolemmal Na(+)-Ca2+ exchanger activity. This defect limits the ability of of the diabetic heart to extrude calcium, contributing to an elevation in [Ca2+]i. Also promoting the accumulation of calcium by the diabetic cell is a decrease in Na+, K+ ATPase activity, which is known to increase [Ca2+]i secondary to a rise in [Na+]i. In addition, calcium influx via the calcium channel is stimulated. Although the molecular mechanisms underlying these defects are presently unknown, the possibility that they may be related to aberrations in glucose or lipid metabolism are considered. The evidence suggests that classical theories of glucose toxicity, such as excessive polyol production or glycosylation, appear to be insignificant factors in heart. Also insignificant are defects in lipid metabolism leading to accumulation of toxic lipid amphiphiles or triacylglycerol. Rather, the major defects involve membrane changes, such as phosphatidylethanolamine N-methylation and protein phosphorylation, which can be attributed to the state of insulin resistance.
...
PMID:Cardiomyopathy associated with noninsulin-dependent diabetes. 166 89


1 2 3 4 5 6 7 8 9 10 Next >>

---