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)

Mechanisms determining the natriuresis in ECV expansion are not yet completely known. The present study was therefore performed to investigate (1) the extent to which prostaglandins (PG) are involved in the natriuresis of ECV expansion and (2) by which mechanisms PG may affect renal Na absorption. In nonexpanded rats the prostaglandin synthetase inhibitor indomethacin (INDO) had no effect on renal function. In 16 Sprague-Dawley rats EVC expansion with isotonic saline corresponding to an increase in body weight of 10% was induced and maintained for 60 min. Ten animals received an oral dose of 10 mg/kg BW of INDO prior to ECV expansion. Six animals served as controls (C). Blood pressure (INDO: 132 +/- 4 (SE); C: 130 +/- 3 mm Hg), GFR (INDO: 12.5 +/- 1.0; C: 10.5 +/- 0.9 ml/min/kg BW), fractional K excretion (INDO: 32.1 +/- 2.6; C: 43.4 +/- 4.8%), CH2O and Na-k-ATPase activities in renal cortex, medulla and papilla did not significantly differ in either group. Significant differences were observed in urinary flow rate (INDO: 0.82 +/- 0.8; C: 1.82 +/- 0.23 ml/min/kg KG) and fractional Na absorption (INDO: 91.9 +/- 1.1; C: 81.7 +/- 1.2%). The results indicate that PG are involved in the natriuresis following acute expansion of the ECV and suggest that PG may inhibit the intrinsic tubular capacity for Na absorption in the rat.
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PMID:The role of prostaglandins in the natriuresis of acutely salt-loaded rats. 85 79

Previous studies have suggested the presence of an H(+)-K(+)-ATPase in rat cortical and medullary intercalated cells with similar properties to the gastric proton pump. The purpose of this study was to determine the functional contribution of an H(+)-K(+)-adenosinetriphosphatase(ATPase) to total CO2 (tCO2) transport along the rat collecting duct. After baseline determination of tCO2 transport in isolated perfused collecting duct segments, Sch 28080 (10 microM) was added to either the perfusate or bath. When Sch 28080 was added to the perfusate, there was no effect in the cortical collecting duct (CCD, 20.8 +/- 6.7 vs. 25.3 + 3.0 pmol.mm-1.min-1), but a marked decrease in tCO2 absorption was effected in both the outer medullary (OMCD, 37.6 + 6.2 vs. 10.7 +/- 4.1 pmol.mm-1.min-1) and initial inner medullary collecting duct (IMCD1, 34.4 +/- 8.1 vs. 16.2 +/- 5.6 pmol.mm-1.min-1). In the CCD from rats with acute alkalosis in vivo, Sch 28080 added to the bath inhibited tCO2 secretion in the CCD (-17.1 +/- 4.4 vs 3.5 + 3.3 pmol.mm-1.min-1). These findings suggest that 1) H(+)-K(+)-ATPase is important in tCO2 absorption in the OMCD and IMCD1 and in tCO2 secretion in the CCD, 2) HCO3(-)-absorbing intercalated cells differ functionally in the cortex and medulla, 3) HCO3- secretion is not the reverse process of HCO3- absorption in the CCD, and 4) H(+)-K(+)-ATPase is important in distal acidification under normal and altered acid-base conditions.
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PMID:H(+)-K(+)-ATPase activity in rat collecting duct segments. 131 8

The activity of Na+/H(+)-exchange and H(+)-ATPase was measured in the absence of CO2/HCO3 by microfluorometry at the single cell level in rat proximal tubules (superficial S1/S2 segments) loaded with BCECF [2'7'-bis(carboxyethyl)5-6-carboxyfluorescein- acetoxymethylester]. Intracellular pH (pHi) was lowered by a NH4Cl-prepulse technique. In the absence of Na+ in the superfusion solutions, pHi recovered from the acid load by a mechanism inhibited by 0.1 microM bafilomycin A1, a specific inhibitor of a vacuolar-type H(+)-ATPase. Readdition of Na+ in the presence of bafilomycin A1 produced an immediate recovery of pHi by a mechanism sensitive to the addition of 10 microM EIPA (ethylisopropylamiloride), a specific inhibitor of Na+/H+ exchange. The transport rate of the H(+)-ATPase is about 40% of Na+/H(+)-exchange activity at a similar pHi (0.218 +/- 0.028 vs. 0.507 +/- 0.056 pH unit/min. Pre-exposure of the tubules to 30 mM fructose, 0.5 mM iodoacetate and 1 mM KCN (to deplete intracellular ATP) prevented a pHi recovery in Na(+)-free media; readdition of Na+ led to an immediate pHi recovery. Tubules pre-exposed to Cl(-)-free media for 2 hr also reduced the rate of Na(+)-independent pHi recovery. In free-flow electrophoretic separations of brush border membranes and basolateral membranes, a bafilomycin A1-sensitive ATPase activity was found to be associated with the brush border membrane fraction; half maximal inhibition is at 6 x 10(-10) M bafilomycin A1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:H+ extrusion by an apical vacuolar-type H(+)-ATPase in rat renal proximal tubules. 131 56

Osteoclasts are primary cells responsible for bone resorption. The most characteristic feature of osteoclasts is the presence of ruffled borders and clear zones. The resorbing area under the ruffled border of osteoclasts is acidic, which favors dissolution of bone mineral. In bone-resorbing osteoclasts, hydrogen ions are provided by carbonic anhydrase II, which catalyzes the hydration of CO2 to H2CO3. Recently, it has been shown that the proton pump of the vacuolar H(+)-ATPase type exists in the ruffled border membranes of osteoclasts. Secretion of hydrogen ions by osteoclasts generates an equal amount of cytoplasmic base equivalents, principally as HCO3-. Osteoclasts have a chloride/bicarbonate exchanger, which normalizes the intracellular pH when osteoclasts actively resorb bone. In this paper, we review the mechanism of the acid secretion by osteoclasts.
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PMID:[Mechanism of acid production and secretion by osteoclasts]. 133 70

Multiple lines of evidence support the hypothesis that the outer medullary collecting duct from the inner stripe (OMCDi) possesses a functional proton-potassium-activated adenosinetriphosphatase (H-K-ATPase). To examine the effect of inhibition of H-K-ATPase on Rb efflux, we measured the Rb tracer rate efflux coefficient (KRb) across the OMCDi of animals adapted to a K-restricted diet using the selective K-competitive H-K-ATPase inhibitor, Sch 28080. Sch 28080 (10 microM) did not significantly alter transepithelial voltage (VT) but significantly decreased KRb by 41%. We further examined the effect of 10% peritubular CO2 on KRb and the subsequent effect of Sch 28080 (10 microM) on KRb. After exposure to 10% CO2 for 120 min, vehicle-treated tubules exhibited a small but significant increase in KRb without a significant change in VT. In contrast, 10 microM Sch 28080 significantly decreased KRb by 44% without affecting VT. The lack of an effect of H-K-ATPase inhibition on VT in the presence of either 5% or 10% CO2 was in marked contrast to the effect of carbonic anhydrase inhibition (CAI). CAI consistently and significantly decreased VT either in the presence of 5% or 10% CO2. To address whether H-K-ATPase also participates in proton secretion we examined the effect of Sch 28080 (10 microM) on net bicarbonate absorption by the OMCDi of rabbits fed a normal rabbit ration and rabbits adapted to a K-restricted diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rubidium absorption and proton secretion by rabbit outer medullary collecting duct via H-K-ATPase. 133 4

The present study was designed to test whether tubular carbon dioxide production from the carbon skeleton of uniformly 14C-labelled glutamine exhibits quantitative and qualitative segmental heterogeneity. Our results show that CO2 production from glutamine in the proximal convoluted tubule (PCT) was dependent on substrate concentrations and is saturable at 10(-4) M of glutamine. Glutamine oxidation was demonstrable in all nephron segments examined. The PCT is the quantitatively predominant site of glutamine oxidation. Intermediate nephron segments, however, such as the thick ascending limb (MAL) and the distal convoluted tubule possess a significant capacity for glutamine oxidation, particularly when examined in terms of tubular protein content. Modulation of glutamine oxidation by extracellular pH was segment specific. Stimulation by acidosis and inhibition by alkalosis were observed in the PCT while carbon dioxide production from glutamine in the MAL was pH-insensitive. Glutamine oxidation was closely linked to sodium transport and greatly decreased by inhibition of Na-K-ATPase. In both the PCT and MAL, glutamine oxidation was inhibited by high extracellular potassium concentrations and in the PCT enhanced by extracellular hypokalemia. N-Ethyl maleiamide, an inhibitor of proton ATPase, led to almost complete cessation of CO2 production from the substrate in both PCT and MAL. Acetazolamide, an inhibitor of carbonic anhydrase, led to a partial reduction in carbon dioxide formation in the PCT, but did not affect glutamine oxidation in the MAL. We conclude that segmental qualitative heterogeneity characterizes oxidation of the carbon skeleton of glutamine with proximal segments showing the predictable effects of pH changes and carbonic anhydrase inhibition. The MAL appears to be nonmodulating.
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PMID:Tubular CO2 production from glutamine in the rat: segmental profile and modulation. 137 65

pH regulatory mechanisms in primary cultures of astrocytes from the cerebral cortex of neonatal audiogenic-seizure-susceptible DBA/2J (DBA) and genetically controlled C57BL/6J (C57) mice were studied with [14C]dimethyloxazolidine-2-4-dione (DMO) and [3H]-methyl-D-glucose (MDG). Effects of changing the concentration of Na+, K+, HCO3- or Cl- in medium, and/or of different transport blockers and metabolite inhibitor on intracellular pH (pHi) of cultured astrocytes were also studied. In nominal HCO3(-)-free HEPES-buffered Hanks' balanced salt solution (HEPES HBSS), when the pH of medium (pHo) was maintained at 7.4, the steady-state pHi of cultured astrocytes from DBA mice was 6.98 +/- 0.03, and that from C57 mice was 7.01 +/- 0.03. When the cells were incubated in HBSS containing 25 mM HCO3- and equilibrated with 5% CO2 (HCO3- HBSS, pHo = 7.4), pHi of both DBA and C57 astrocytes was approximately 0.1-0.15 pH units higher than that in HEPES HBSS. Reducing the pH or the Na+ concentration in media (pHo, [Na+]o) of either HEPES HBSS or HCO3- HBSS, pHi of both DBA and C57 astrocytes decreased markedly (0.25-0.45 pH units lower than the controls). The decrease in pHi was greater in HEPES HBSS than in HCO3- HBSS. Reducing the Cl- concentration ([Cl-]o) in either HEPES or HCO3- HBSS, pHi of astrocytes increased by 0.05-0.1 pH units. Increasing the K+ concentration ([K+]o) of or adding Ba2+ to the media increased the pHi of both DBA and C57 astrocytes accordingly. SITS, an anion transport inhibitor, decreased the pHi of both DBA and C57 astrocytes in HCO3- HBSS but not in HEPES HBSS. It enhanced the response of pHi to reduction in pHo. Amiloride, a Na(+)-H+ exchange inhibitor, decreased the pHi of both DBA and C57 astrocytes more in HEPES HBSS than in HCO3- HBSS. It enhanced the response of pHi to reduction in pHo and [Na+]o. Ouabain, an Na+,K(+)-ATPase inhibitor, decreased the pHi of cultured astrocytes in HEPES HBSS, but not in HCO3- HBSS. It also enhanced the response of pHi to changing pHo and [Na+]o in HEPES HBSS. Acetazolamide, a carbonic anhydrase inhibitor, decreased the pHi of astrocytes in both HEPES and HCO3- HBSS. Both bumetanide, an Na+,K+/Cl- cotransport blocker, and KCN, a metabolic inhibitor, produced no significant effect on the steady-state pHi or the response of pHi to changing ionic concentration in media in both DBA and C57 astrocytes.
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PMID:Studies on pH regulatory mechanisms in cultured astrocytes of DBA and C57 mice. 139 16

Intracellular pH (pHi) of acid-secreting cells was measured in intact gastric fundus mucosa of Rana esculenta with double-barrelled pH microelectrodes. Tissues were mounted, serosal side up, between two half chambers and individual cells were impaled after microsurgical removal of the serosal muscle layer. Transepithelial potential difference (Vt) and resistance (Rt) as well as serosal cell membrane potential (Vs) and pHi were continuously recorded at rest (0.1 mmol/l cimetidine) or during stimulation (0.5 mmol/l histamine). During chamber perfusion with HCO3-/CO2-buffered Ringer solution of pHo = 7.36, Vt and Rt were -21.7, SD +/- 6.0 mV and 229 +/- 83 omega cm2 (n = 17) while Vs and pHi averaged -57.3 +/- 6.9 mV and 7.4 +/- 0.11 (n = 25). The latter value is considerably more alkaline than all recent pHi measurements obtained with microspectrofluorometric techniques on isolated cells, glands or intact tissue. The difference may in part be explained by use of HCO3(-)-free solutions in most of the previous studies because we observed that such solutions decrease pHi to 6.89 +/- 0.18 (n = 4). Again, in contrast to recent literature, application of histamine in HCO3-/CO2-buffered solution led to further transient alkalinization by 0.12 +/- 0.05 pH unit (n = 8). Since in accidental punctures of the gastric gland lumen we noticed that H+ secretion only began approximately 5 min after histamine application, we conclude that the histamine-induced initial alkalinization does not reflect stimulation of the H+/K+ ATPase pump.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microelectrode determination of oxyntic cell pH in intact frog gastric mucosa. Effect of histamine. 148 84

The frog skin in vivo is capable of active transepithelial H+ secretion (JH) which is matched by Na+ absorption (JNa). Studies in vitro demonstrate that JH is generated by an H(+)-ATPase pump localized in apical membranes of mitochondria-rich (MR) cells, whereas JNa occurs through an amiloride-sensitive pathway in principal (P) cells. The H+ pump is sensitive to inhibitors of carbonic anhydrase (e.g. acetazolamide) and to specific inhibitors of mitochondrial F1F0 H(+)-ATPase (oligomycin) and vacuolar (V)-type H(+)-ATPase (N-ethylmaleimide) and to inhibitors of both these types of H(+)-ATPases (dicyclohexylcarbodiimide, DCCD). JH is independent of external K+, which differentiates it from gastric H+/K(+)-ATPase and is strictly dependent on aerobic metabolism. The proton pump is primarily implicated in whole-body acid-base regulation. Acute stimulation of JH in response (seconds-minutes) to an acid load involves insertion of H+ pumps (exocytosis) from a cytosolic pool into the apical membrane. The chronic response (days) to metabolic acid load involves morphological changes (increased apical membrane surface area and number of MR cells). Whole-cell patch-clamp recordings of membrane capacitance and current fluctuations from MR cells demonstrate that a respiratory acid load and aldosterone produce rapid exocytotic insertion of DCCD-sensitive conductive membrane. A secondary role of the H+ pump is to energize sodium absorption (JNa) via principal cells from dilute solutions in the absence of a permeant anion under open-circuit conditions. The apparent 1:1 stoichiometry between JH and JNa is a result of transepithelial electrical coupling between these electrogenic fluxes. The H+ pump in MR cells generates a transepithelial current (serosa to apical) which acts as a physiological voltage-clamp to hyperpolarize the apical membrane of P cells. This hyperpolarization can facilitate passive Na+ entry across the apical membrane against a threefold chemical gradient. Since both JH and JNa are sensitive to membrane potential, inhibition or activation of one will produce similar effects on the transport of the other ion. For example, inhibition of JH by ethoxzolamide will reduce JNa. Conversely, blocking JNa with amiloride also inhibits JH. These effects can be avoided or reversed if variations in membrane potential are prevented by voltage-clamping the epithelium. A paradoxical activation of JNa is observed when JH is stimulated by an acid load (CO2), despite inhibition of Na+ channel activity by H+ in P cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Energization of sodium absorption by the H(+)-ATPase pump in mitochondria-rich cells of frog skin. 149 Dec 27

HCO3-/CO2 can affect proximal tubule energy metabolism directly by serving as a substrate for metabolic reactions and indirectly through ATP utilization by HCO3(-)-coupled Na+ reabsorption and proton secretion. In this study, metabolic and transport roles of HCO3-/CO2 were examined by measuring the effects of HCO3-/CO2 removal and transport inhibitors on oxygen consumption (QO2) in suspensions of rabbit proximal tubules. Removal of medium HCO3-/CO2 inhibited ouabain-sensitive, ouabain-insensitive, and uncoupled QO2. Consistent with metabolic inhibition, the absence of HCO3-/CO2 also reduced tubule ATP content and stimulated lactate production. Analysis of the dependence of mitochondrial state 3 respiration on HCO3-/CO2 in digitonin-permeabilized tubules traced the metabolic inhibition to limitations in tricarboxylic acid cycle intermediate supply. Energy requirements for HCO3- transport were examined by measuring QO2 in response to acetazolamide, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), and the H(+)-adenosinetriphosphatase (H(+)-ATPase) inhibitor bafilomycin A. Acetazolamide had no effect on QO2, whereas DIDS-SITS and bafilomycin A reduced ouabain-insensitive QO2, consistent with inhibition of active proton secretion. DIDS-SITS did not affect ouabain-sensitive respiration, suggesting that HCO3(-)-dependent Na+ reabsorption may not be mediated through the Na(+)-K(+)-ATPase in this preparation.
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PMID:Relationship between HCO3- transport and oxidative metabolism in rabbit proximal tubule. 151 Jan 26


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