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)

Three different mechanisms interact to control the cytosolic pH (pHi) of alveolar macrophages (M phi), namely, plasmalemmal vacuolar-type H(+)-ATPase (V-ATPase), Na+/H+ exchange, and Na(+)-independent HCO3-/Cl- exchange. To investigate the activity of plasmalemmal V-ATPase in alveolar M phi, we developed a nonlinear mathematical model of pHi regulation that incorporates the biophysical determinants of pHi and the fluxes of individual acid-base equivalents. The model was used to analyze the acid-base responses of rabbit alveolar M phi to a weak acid (propionic acid) under conditions that favored V-ATPase-mediated effects (presence of 1 mM amiloride and nominal absence of CO2). The pHi was measured using the fluorescent probe, 2',7'-biscarboxethyl-5,6-carboxyfluorescein. M phi exposure to propionic acid caused a rapid fall in pHi. Recovery of pHi after acid loading varied directly with the magnitude of the acid load. Mathematical analyses showed that pHi recovery was hindered by persistent influx of propionic acid driven, in turn, by transporter-mediated H+ extrusion and propionate efflux. Eventually, a new steady state was established in which propionate and H+ were cycled out of the M phi and propionic acid was recycled into the cell. As a consequence, model predictions of the rate of V-ATPase-mediated H+ efflux were almost twice that estimated from experimental determinations of the initial rate of pHi recovery.
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PMID:Kinetic analysis of cytosolic pH regulation in alveolar macrophages: V-ATPase-mediated responses to a weak acid. 763 10

There is now convincing evidence that in addition to the vacuolar-type H(+)-ATPase, a gastric-type H+/K(+)-ATPase participates in acidification by the distal nephron. To determine whether a similar pump exists in the turtle bladder, we examined the dependence of acid secretion on mucosal K+, and the effects of supposedly specific inhibitors of the gastric H+/K(+)-ATPase, omeprazole and SCH 28080. In CO2-stimulated bladders both drugs produced dose-dependent inhibition of electrogenic H+ secretion measured as the reverse short-circuit current (RSCC). At the highest concentrations tested, H+ secretion decreased 45 +/- 16% with mucosal and 20 +/- 7% with serosal omeprazole (P < 0.01). SCH 28080 at 400 microM produced essentially complete inhibition of H+ secretion with either mucosal or serosal application. When H+ secretion was purposefully inhibited by DIDS or an adverse mucosal pH gradient, SCH 28080 had no effect on RSCC. Removing mucosal K+ (measured K+ < 50 microM), with or without mucosal barium, had no effect on RSCC. The inhibition of RSCC by omeprazole was reversed by mercaptoethanol. Finally, HCO3 secretion, as measured by either RSCC or pH-stat titration, increased significantly in response to 400 microM SCH 28080. The results demonstrate that these compounds inhibit acid secretion by the turtle bladder but stimulate the secretion of base. In view of the total independence of acid secretion on potassium, it is unlikely that any of the bladder's acid secretion is mediated by an H+/K(+)-ATPase. The most reasonable interpretation of the data is that omeprazole and SCH 28080, previously thought to be specific inhibitors of the H+/K(+)-ATPase, also inhibit the vacuolar H(+)-ATPase of the turtle bladder. The results also indicate that HCO3 secretion by the bladder employ a different mechanism of H+ transport than is used for acid secretion; there is no simple reversal of polarity in the acid- versus base-secreting cells.
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PMID:Omeprazole and SCH 28080 inhibit acid secretion by the turtle urinary bladder. 769 39

Vacuolar membrane vesicles were isolated from Candida albicans protoplasts, and marker enzyme assays were employed to identify the membranes as vacuolar in origin. The mechanisms of Ca2+ uptake and Ca2+ release at the vacuolar membrane were investigated. Ca2+ accumulation by vacuolar membrane vesicles can be generated via H+/Ca2+ antiport. The inside-acid pH is in turn generated by a vacuolar-type H(+)-ATPase, as demonstrated by the sensitivity of Ca2+ uptake to ionophores and the vacuolar H(+)-ATPase inhibitor bafilomycin A1. Vacuolar membrane vesicles exhibit two Ca2+ release pathways: one induced by inositol 1,4,5-trisphosphate (InsP3) and the other by inside-positive voltage. These two pathways are distinct with respect to the amount of Ca2+ released, the nature of response to successive stimuli, and their respective pharmacological profiles. The InsP3-gated pathway exhibits a K0.5 for InsP3 of 2.4 microM but is not activated by inositol 4,5-bisphosphate or inositol 1,3,4,5-tetrakisphosphate at concentrations up to 50 microM. Ca2+ release by InsP3 is blocked partially by low molecular weight heparin. Ca2+ released by the voltage-sensitive pathway occurs at membrane potentials estimated to be over a physiological range from 0 to 80 mV. The voltage-sensitive Ca2+ release pathway can be blocked by lanthanide ions and organic channel blockers such as ruthenium red and verapamil. Furthermore, the voltage-sensitive Ca2+ release pathway exhibits Ca(2+)-induced Ca2+ release. These findings are discussed in relation to the mechanism of Ca(2+)-mediated cellular signaling in C. albicans and other fungi.
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PMID:Inositol trisphosphate-dependent and -independent Ca2+ mobilization pathways at the vacuolar membrane of Candida albicans. 770 67

It is well established that osteoclasts use a vacuolar-type H(+)-ATPase (V-ATPase) for proton pumping during bone resorption and that specific V-ATPase inhibitors such as bafilomycin A1 abolish osteoclastic bone resorption in the bone slice assay. It has been reported that the V-ATPase in avian osteoclasts can be distinguished from the V-ATPase expressed in most other cells, by virtue of its inhibition by vanadate and nitrate ions. In order to determine whether the V-ATPase in mammalian osteoclasts can be similarly distinguished, we have investigated the effects of vanadate and nitrate on bone resorption by rat osteoclasts in the bone slice assay, in comparison with known V-ATPase inhibitors, bafilomycin A1 and WY 47766, that also inhibit the chicken osteoclast V-ATPase. The results indicate that, unlike the avian osteoclast V-ATPase, the mammalian osteoclast V-ATPase is pharmacologically similar to the V-ATPase in other cells.
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PMID:A pharmacological assessment of the mammalian osteoclast vacuolar H(+)-ATPase. 771 23

Calcium uptake by microsomal membranes from the cellular slime mould Dictyostelium discoideum was measured using Calcium Green-2 as a fluorescent probe of external free Ca2+ concentration. High-affinity Ca2+ uptake was found to be completely inhibited by low concentrations of vanadate, but not by thapsigargin, suggesting that the activity is mediated by a Ca(2+)-ATPase distinct from sarco(endo)plasmic reticulum type of higher animal cells. On sucrose density gradients, Ca2+ uptake distributes with vacuolar proton pump activity and part of the observed Ca2+ uptake is dependent on the pH gradient generated by the vacuolar-type H(+)-ATPase, indicating that the Ca2+ pump is located on both acidic and non-acidic vesicles, possibly derived from the H(+)-ATPase-rich contractile vacuole complex.
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PMID:Characterisation of an intracellular Ca2+ pump in Dictyostelium. 771 44

The roles of protein kinase C (PKC) in regulation of the plasmalemmal vacuolar-type H(+)-ATPase (V-ATPase) and Na(+)-H+ exchanger (NHE) of rabbit alveolar macrophages (m phi) were investigated using phorbol 12-myristate 13-acetate (PMA). At an extracellular pH (pHo) of 7.4 (nominal absence of CO2-HCO3-), PMA caused a dose-dependent increase in the rate of cellular H+ extrusion with little change in intracellular pH (pHi). PMA caused a prolonged cytosolic acidification at pHo < or = 6.8. PMA-induced changes in pHi were sensitive to bafilomycin A1, but were insensitive to amiloride. Studies of pHi recovery following intracellular acid challenge showed that both V-ATPase and the NHE were up-regulated by PMA. An inactive analog, 4 alpha-phorbol, had no detectable effects on pHi homeostasis. These data indicate that (a) PKC is involved in regulation of V-ATPase and the NHE of resident alveolar m phi and (b) V-ATPase is the predominant mechanism for pHi homeostasis in unstimulated and PMA-activated m phi.
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PMID:Effects of myristate phorbol ester on V-ATPase activity and Na(+)-H+ exchange in alveolar macrophages. 772 18

Carbonic anhydrase (CA) activity was localized in the salivery glands of the cockroach, Periplaneta americana, by (1) Hansson's histochemical technique, and (2) the use of the fluorescent sulphonamide, 5-dimethyl-amino-naphthalene-1-sulphonamide (DNSA). Both techniques reveal the same distribution pattern of CA in the four morphologically different cell types of the glands: peripheral cells, central cells, inner acinar duct cells, and distal duct cells. Positive reactions with Hansson's cobalt/phosphate technique were found in the apical regions of the peripheral cells and the distal duct cells, and were inhibited by 10(-5) M acetazolamide in control experiments. No staining could be detected in the central cells and the inner acinar duct cells. The fluorescent CA inhibitor DNSA (10(-4)M) specifically stained the peripheral cells and the distal duct cells in methanol-fixed cryostat sections, whereas the central cells and the inner acinar duct cells remained unstained. The role of CA in the peripheral cells is not clear. CA activity in the distal duct cells may provide the protons needed to run the vacuolar-type H(+)-ATPase on the apical infoldings of the cells. This ATPase may be involved in modification of the primary saliva.
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PMID:Localization of carbonic anhydrase in the salivary glands of the cockroach, Periplaneta americana. 784 90

Resident alveolar macrophages (m phi) possess plasmalemmal vacuolar-type H(+)-ATPase (V-ATPase) that plays a crucial role in regulation of intracellular pH (pHi). To assess the importance of this V-ATPase to m phi effector functions, resident alveolar m phi from rabbits were activated with E. coli-derived lipopolysaccharide (LPS) and exposed to bafilomycin A1, a specific inhibitor of V-ATPase. Bafilomycin caused a significant cytosolic acidification in both the absence and presence of CO2-HCO3-, and in both unstimulated and activated m phi. Superoxide production and Fc receptor-mediated phagocytosis also were reduced in bafilomycin-treated m phi. Similar effects were elicited by acidifying the cytoplasm in the absence of bafilomycin, by lowering extracellular pH (pHo) from 7.4 to 6.5-6.6. Thus, the effects of bafilomycin on phagocytosis and superoxide production probably were related to cytosolic acidification, secondary to blockade of V-ATPase-mediated H+ extrusion across the plasma membrane. Conversely, bafilomycin significantly increased TNF-alpha release. This effect cannot be explained by a bafilomycin-induced acidosis because acidic pHo significantly reduced TNF-alpha release. The results demonstrate that V-ATPase activity is an important determinant of the effector functions of LPS-activated m phi.
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PMID:Effects of bafilomycin A1 on functional capabilities of LPS-activated alveolar macrophages. 785 42

The acinous salivary glands of the cockroach (Periplaneta americana) consist of four morphologically different cell types with different functions: the peripheral cells are thought to produce the fluid component of the primary saliva, the central cells secrete the proteinaceous components, the inner acinar duct cells stabilize the acini and secrete a cuticular intima, whereas the distal duct cells modify the primary saliva via the transport of water and electrolytes. Because there is no direct information available on the distribution of ion transporting enzymes in the salivary glands, we have mapped the distribution of two key transport enzymes, the Na+/K(+)-ATPase (sodium pump) and a vacuolar-type H(+)-ATPase, by immunocytochemical techniques. In the peripheral cells, the Na+/K(+)-ATPase is localized to the highly infolded apical membrane surface. The distal duct cells show large numbers of sodium pumps localized to the basolateral part of their plasma membrane, whereas their highly folded apical membranes have a vacuolar-type H(+)-ATPase. Our immunocytochemical data are supported by conventional electron microscopy, which shows electron-dense 10-nm particles (portasomes) on the cytoplasmic surface of the infoldings of the apical membranes of the distal duct cells. The apically localized Na+/K(+)-ATPase in the peripheral cells is probably directly involved in the formation of the Na(+)-rich primary saliva. The latter is modified by the distal duct cells by transport mechanisms energized by the proton motive force of the apically localized V-H(+)-ATPase.
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PMID:Immunocytochemical localization of Na+/K(+)-ATPase and V-H(+)-ATPase in the salivary glands of the cockroach, Periplaneta americana. 795 97

Ascidians belonging to the family Ascidiidae are known to accumulate vanadium from seawater in their blood cells, concentrating vanadium by a factor of 10(7). Among several different types of blood cell, the signet ring cells have both high levels of vanadium and a low pH. These observations suggest the possibility that proton ions concentrated by a H(+)-ATPase are energetically linked to the accumulation of vanadium. In the present experiments, therefore, we made an immunological search for a H(+)-ATPase in the vacuolar membranes of the signet ring cells, as a first step in our attempts to clarify the energetics of the accumulation of vanadium by these cells. Antibodies raised against the 72-kDa and 57-kDa subunits of a vacuolar-type H(+)-ATPase from bovine chromaffin granules reacted with the vacuolar membranes of signet ring cells. Immunoblotting analysis confirmed that specific antigens in ascidian blood cells actually reacted with the antibodies. Furthermore, addition of bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibited the uptake of protons by the vacuoles of signet ring cells. Thus, the addition of bafilomycin A1 inhibited the pumping function of the vacuoles of signet ring cells, with resultant neutralization of the contents of the vacuoles.
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PMID:Immunological detection of a vacuolar-type H(+)-ATPase in vanadocytes of the ascidian Ascidia sydneiensis samea. 796 52


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