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)

Stimulation of pig peripheral blood lymphocytes with concanavalin A (Con A) provoked a rapid increase (two- to threefold) in the rate of ouabain-inhibitable K+ uptake observable within 3-10 min of stimulation with mitogen. At least two phases can be distinguished in the activation of the Na+/K+ pump: the early phase (till 3 h) is characterized by an unaltered number of ouabain binding sites and the later phase (noted at 5 h) by an increased number of such sites. Both K+ efflux and influx increased to the same extent, thereby maintaining [K+]i at the same level as in resting cells (120 mM). Within 3 min of addition of mitogen, the rates of total and amiloride-inhibitable Na+ uptake went up two- and fourfold, respectively, thus resulting in rapid increase in [Na+]i from 20 to about 50 mM. Activation of the Na+/K+ pump was not observed when the cells were stimulated with Con A in low Na+ medium (9 mM), nor did the usual rise in [Na+]i occur. When monensin (30 microM), a Na+/H+ ionophore, was added to resting cells, an increase in both [Na+]i and active K+ uptake occurred in normal medium but not when cells were suspended in low Na+ isotonic buffer. Amiloride (500 microM), on the other hand, prevented both the Con A-induced increase in [Na+]i and the activation of the Na+/K+ pump. Despite complete inhibition of the Na+,K+-ATPase in the presence of ouabain (1 mM), Con A activated the amiloride-inhibitable Na+ uptake in the usual way. In mouse splenocytes stimulated with Con A, there was also a parallel rise in both [Na+]i and active K+ uptake but this took considerably longer to occur than was the case in pig peripheral blood lymphocytes. Increase in both ionic fluxes, the former passive and the latter active, is essential to the entry and maintenance of the cells in proliferative cycle.
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PMID:Sodium ion influx in proliferating lymphocytes: an early component of the mitogenic signal. 302 70

myo-Inositol uptake was investigated in a murine neuroblastoma clone (N1E-115) to determine the effect of altered Na+,K+-ATPase activity. The Na+ ionophore monensin, and veratridine, an alkaloid affecting voltage-dependent Na+ entry, increased acute 22Na+ uptake and 22Na+ efflux from pre-loaded cells, concomitant with enhanced myo-inositol uptake. This effect was also seen following insulin. Insulin-stimulated myo-inositol uptake was inhibited by amiloride, ouabain and pyrithiamine. Amiloride inhibition suggests that activation of Na+/H+ exchange preceding Na+,K+-ATPase activation is involved in insulin stimulation of myo-inositol uptake. Pyrithiamine inhibition is an indication of prior activation of the Na+,K+-ATPase alpha + catalytic subunit by insulin. The results provide evidence that insulin contributes to the maintenance of Na+,K+-ATPase in neuronal tissue.
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PMID:Acute changes in myo-inositol uptake and 22Na+ flux in murine neuroblastoma cells (N1E-115) following insulin. 330 13

Sodium transport in the papillary collecting duct (PCD) is poorly understood because of the inaccessibility of the distal nephron to micropuncture. Cultured rat renal papillary collecting tubule (RPCT) cells were investigated as a model for the PCD. RPCT cells have the morphologic appearance and hormonal responsiveness of the papillary collecting tubule. Sodium transport was studied using 22Na+ uptake measurements. Sodium uptake, measured at 23 degrees C in the absence of K+ and in the presence of 0.5 mM ouabain, was saturable at 100 mM extracellular NaCl, and half-maximal uptake occurred at 40 mM NaCl. The accumulation of 22Na+ appeared to be intracellular and was regulated by (Na+,K+)-ATPase activity, since activation of the Na+/K+ pump with K+ reduced 22Na+ accumulation by 90%. The time course for uptake was linear, showed only a single component, and followed first order kinetics with a t1/2 of 16 min. Amiloride and lithium inhibited 22Na+ influx, and a Dixon plot was linear, with a Ki of 16 microM amiloride. Chloride replacement of 1 mM furosemide, with or without K+, reduced uptake by only 20%. Sodium efflux from RPCT cells in the presence of ouabain showed a similar time course (t1/2, 15 min) and was also inhibited by amiloride (IC50 = 20 microM). Increased extracellular pH stimulated 22Na+ uptake and inhibited 22Na+ efflux. Addition of permeable organic acids, acetate, and bicarbonate, enhanced 22Na+ uptake. These results are consistent with Na+/H+ and Na+/Na+ exchange as mechanisms of 22Na+ uptake in the RPCT cell. This exchanger may be important in regulation of transepithelial sodium flux, maintenance of intracellular pH and cell volume, and hormonal stimulation of the papillary collecting duct.
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PMID:Sodium transport in rat renal papillary collecting tubule cells in culture. 337 95

Reagents which affect the cytosolic concentrations of protons and sodium ions markedly affect the degranulation process of mast cells. The proton-sodium exchanging ionophore, monensin, is found to cause noncytolytic dose dependent serotonin release from the rat leukemic basophils (line RBL-2H3). Its half maximal dose of ca. 2 microM leads to secretion of ca. 20% of these cells' serotonin content. Monensin induced serotonin secretion increases with external pH and decreases upon lowering external sodium ion concentrations, yet is independent on external calcium. Monitoring cytosolic pH and free Ca2+ concentrations with BCECF and quin2, respectively, shows that a rise in pHi and [Ca2+]i is caused by the ionophore. Amiloride, the blocker of cellular Na+/H+ antiporter, is found to be an effective inhibitor of antigen or monensin induced serotonin release. However, it does not by itself cause secretion. In contrast, ouabain, which inhibits the cellular Na+/K+ ATPase, does induce secretion. Cellular levels of pH, Na+ and Ca2+ ions are evidently linked and involve a manifold of activities. Though exchanging protons for sodium seems to be effective in causing mediator release, the present results do not provide sufficient support for proton/sodium ions having a second messenger role in the immunologically induced mediator release.
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PMID:Mutual relationship among cytosolic pH, Na+ and Ca2+ ions in the degranulation of rat leukemic basophils. 377 Aug 8

Secretion by the parotid gland of Na-replete and -depleted sheep was investigated by examining the effects of modifiers of ionic transfer on salivary composition and flow rate. These agents were infused into the arterial blood supply of the vascularly isolated gland in anesthetized sheep. Ouabain inhibited Na+-K+ exchange in the ducts caused by Na depletion and restored the [Na+], [K+], and osmolality to close to those of Na-replete saliva. Ouabain also inhibited Cl- -HCO3- exchange in the ducts in Na repletion and depletion. Amiloride partially inhibited Na+-K+ exchange in Na depletion without affecting Cl- -HCO3- exchange. Monensin potentiated Na+-K+ exchange in Na repletion and depletion. Amiloride and monensin gained access to the saliva, but furosemide and ethacrynic acid were almost totally excluded, and, up to 10(-3) M in blood, they did not affect salivary composition or flow rate. Methazolamide gained free access to saliva but was without effect. 4-Acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid at 10(-3) M slightly increased salivary [Na+] and [HPO4(2-)]. The results indicate potent effects of ouabain on basolateral Na+-K+ pumps and of amiloride and monensin on transcellular delivery of Na+ to these pumps, but ouabain had no effect on salivary flow rate until O2 consumption approached zero and secretion failed. The findings do not support a proposal that the salivary secretion depends on a Cl- -dependent furosemide-sensitive system energized by Na+-K+-ATPase-dependent Na pumps.
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PMID:Effects of ouabain, amiloride, monensin, and other agents on ovine parotid secretion. 395 28

Frog (Rana temporaria) skins were studied in an Ussing type lucite chamber adapted to diminish tissue edge damage. The transepithelial electrical potential difference, short circuit current and direct current (DC) resistance of skins mounted in this chamber were 56, 20 and 24% higher, respectively, than those of skins mounted in a conventional chamber. Amiloride, triamterene, ouabain and ortho-vanadate inhibited short circuit current and net mucosal to serosal flux of 22Na. Amiloride and triamterene had rapid onsets of action and were effective only when administered to the mucosal (pond) side of the skin. Ouabain and ortho-vanadate had slower onsets of action and were effective only when administered to the serosal side of the skin. Steady state of effects of these drugs was not reached within the three-hour period of the experiments. The inhibitory effect of ortho-vanadate was blocked by adding a disulfonic stilbene derivative (DIDS) to the serosal side of the skin. Serosal prostaglandin E2 stimulated the short-circuit current and decreased the DC resistance. Thiazides, acetazolamide and loop diuretics had no effects on Na+ transport by frog skin. Thus, frog skin seems to be a useful model only in studies of the mode of action and the structure-activity relationship of diuretic which act by inhibiting sodium entry or Na+-K+-ATPase activity.
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PMID:Effects of standard diuretics and ortho-vanadate on sodium transport across isolated frog skin. 609 97

The effects of insulin and glucagon on the (Na+-K+)-ATPase transport activity in freshly isolated rat hepatocytes were investigated by measuring the ouabain-sensitive, active uptake of 86Rb+. The active uptake of 86Rb+ was increased by 18% (p less than 0.05) in the presence of 100 nM insulin, and by 28% (p less than 0.005) in the presence of nM glucagon. These effects were detected as early as 2 min after hepatocyte exposure to either hormone. Half-maximal stimulation was observed with about 0.5 nm insulin and 0.3 nM glucagon. The stimulation of 86Rb+ uptake by insulin occurred in direct proportion to the steady state occupancy of a high affinity receptor by the hormone (the predominant insulin-binding species in hepatocytes at 37 degrees C. For glucagon, half-maximal response was obtained with about 5% of the total receptors occupied by the hormone. Amiloride (a specific inhibitor of Na+ influx) abolished the insulin stimulation of 86Rb+ uptake while inhibiting that of glucagon only partially. Accordingly, insulin was found to rapidly enhance the initial rate of 22Na+ uptake, whereas glucagon had no detectable effect on 22Na+ influx. These results indicate that monovalent cation transport is influenced by insulin and glucagon in isolated rat hepatocytes. In contrast to glucagon, which appears to enhance 86Rb+ influx through the (Na+-K+)-ATPase without affecting Na+ influx, insulin stimulates Na+ entry which in turn may increase the pump activity by increasing the availability of Na+ ions to internal Na+ transport sites of the (Na+-K+)-ATPase.
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PMID:Insulin and glucagon stimulation of (Na+-K+)-ATPase transport activity in isolated rat hepatocytes. 626 50

Amiloride inhibited the ouabain-sensitive rate of oxygen consumption (QO2) of a suspension of rabbit intact proximal tubules in the presence of different concentrations of extracellular sodium. Measurements of the ouabain-sensitive QO2 in the presence of nystatin, the tissue sodium and potassium contents of the tubules in suspension, and the sodium- and potassium-dependent adenosinetriphosphatase (Na,K-ATPase) activity of lysed tubule membranes indicated that the effect of amiloride was due to a direct inhibition of the Na,K-ATPase activity of the proximal tubule.
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PMID:Amiloride directly inhibits the Na,K-ATPase activity of rabbit kidney proximal tubules. 630 40

Brain capillary endothelial cells form a blood-brain barrier (BBB) that appears to play a role in fluid and ion homeostasis in brain. One important transport system that may be involved in this regulatory function is the Na+, K+-ATPase that was previously demonstrated to be present in isolated brain capillaries. The goal of the present study was to identify additional Na+ transport systems in brain capillaries that might contribute to BBB function. Microvessels were isolated from rat brains and 22Na+ uptake by and efflux from the cells were studied. Total 22Na+ uptake was increased and the rate of 22Na+ efflux was decreased by ouabain, confirming the presence of Na+, K+-ATPase in capillary cells. After inhibition of Na+, K+-ATPase activity, another saturable Na+ transport mechanism became apparent. Capillary uptake of 22Na+ was stimulated by an elevated concentration of Na+ or H+ inside the cells and inhibited by extracellular Na+, H+, Li+, and NH4+. Amiloride inhibited 22Na+ uptake with a Ki between 10(-5) and 10(-6) M but there was no effect of 1 mM furosemide on 22Na+ uptake by the isolated microvessels. These results indicate the presence in brain capillaries of a transport system capable of mediating Na+/Na+ and Na+/H+ exchange. As a similar transport system does not appear to be present on the luminal membrane of the brain capillary endothelial cell, it is proposed that Na+/H+ exchange occurs primarily across the antiluminal membrane.
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PMID:Sodium transport in capillaries isolated from rat brain. 631 78

In order to increase our understanding of the mechanism of pancreatic fluid secretion we have studied the effects of various transport inhibitors on this process in the isolated rabbit pancreas. In this preparation, a high rate of unstimulated fluid secretion occurs, which probably originates from the ductular cells. Inhibitory are ouabain, furosemide, bumetanide, piretanide, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) and acetazolamide, with their half-inhibitory concentrations: 2 X 10(-6) M (ouabain), 1.3 X 10(-3) M (furosemide), 2.2 X 10(-3) M (bumetanide and piretanide) and 1.4 X 10(-4) M (SITS). With acetazolamide a maximal inhibition of only 20% is found at 10(-3) M. Amiloride (10(-3) M) has no effect on pancreatic fluid secretion. The inhibitory effects on HCO-3 output are always larger and those on Cl- output lower than those on fluid secretion. The results suggest that the ouabain-sensitive (Na+ + K+)-ATPase system provides the energy for a Na+-gradient-driven Cl--HCO-3-exchange transport system, sensitive to the loop diuretics furosemide, bumetanide and piretanide and to SITS. This system would drive the transcellular transport of HCO-3 and secondarily that of cations, Cl- and water.
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PMID:The mechanism of fluid secretion in the rabbit pancreas studied by means of various inhibitors. 649 95


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