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)

The membrane location and mechanism of inositol 1,3,4,5-tetrakisphosphate (InsP4)-regulated Ca2+ uptake in cardiac membrane vesicles was investigated. In canine and rat membranes separated by sucrose density gradient centrifugation, InsP4-regulated Ca2+ uptake was slightly more enriched in low density than in higher density membranes. Membranes supporting InsP4-regulated Ca2+ uptake were correspondingly enriched in type 1 InsP3 receptors. Junctional sarcoplasmic reticulum (J-SR), enriched in sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) and ryanodine receptors, separated predominantly with higher density membranes. In membranes supporting InsP4-regulated Ca2+ uptake, Ca2+ uptake was facilitated by a high Ca2+ affinity carrier that was insensitive to thapsigargin. Ca2+ uptake in J-SR was mediated by thapsigargin-sensitive SERCA2a. Net Ca accumulation was enhanced by oxalate in both SR subtypes. Although Ca2+-carrier-mediated Ca2+ uptake was ATP independent, ATP indirectly regulated net Ca2+ accumulation by modifying Ca2+ efflux via a Ca2+ channel with properties of type 1 InsP3 receptors. In the presence of < or = 0.1 mM ATP, InsP4 enhanced Ca2+ accumulation whereas InsP4 inhibited Ca2+ uptake at higher ATP concentrations. In the presence of 0.15 mM ATP, InsP4 stimulated Ca2+ efflux from vesicles preloaded with Ca. Several other InsP4 isomers and 1,3,4-InsP3 also stimulated Ca2+ efflux but with slightly less potency than 1,3,4,5-InsP4. Ruthenium red enhanced net Ca accumulation by the Ca2+ carrier and reduced the potency of ATP, InsP4, and InsP3 to stimulate Ca2+ efflux in vesicles. In summary, this investigation shows that a Ca2+ carrier facilitates Ca loading in a sarcoplasmic reticulum subtype distinct from J-SR. InsP4 and InsP3 are proposed to regulate Ca2+ efflux in low density SR by acting on an ATP-modulated Ca2+ channel with properties of type 1 InsP3 receptors.
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PMID:Inositol polyphosphates regulate Ca2+ efflux in a cardiac membrane subtype distinct from junctional sarcoplasmic reticulum. 1114 29

In lepidopteran larvae, three transport mechanisms are involved in the active and electrogenic K(+) secretion that occurs in the epithelial goblet cells of the midgut. These consist of (i) basolateral K(+) channels, allowing K(+) entry from the haemolymph into the cytosol, (ii) apical electrogenic K(+)/2H(+) antiporters, which are responsible for secondary active extrusion of K(+) from the cell into the gut lumen via the goblet cavity and (iii) apical V-ATPase-type proton pumps. The latter energize apical K(+) exit by building up a large, cavity-positive electrical potential that drives the antiporters. Net K(+) secretion (I(K)) can be measured as short-circuit current (I(sc)) across the in vitro midgut mounted in an Ussing chamber. We investigated the influence of protons on the transepithelial I(K) and the partial reactions of the basolateral K(+) permeability (P(K)) and the apical, lumped 'K(+) pump' current (I(P)) at various extra- and intracellular pH values. In particular, we wanted to know whether increased cellular acidity could counteract the reversible dissociation of the V-ATPase into its V(1) and V(o) parts, as occurs in yeast after glucose deprivation and in the midgut of Manduca sexta during starvation or moulting, thus possibly enhancing K(+) transport. When intact epithelia were perfused with high-[K(+)] (32 mmol l(-1)) salines with different pH values, I(K) was reversibly reduced when pH values fell below 6 on either side of the epithelium. Attempts to modify the intracellular pH by pulsing with NH(4)(+) or propionate showed that intracellular acidification caused a reduction in I(K) similar to that obtained in response to application of external protons. Treatment with azide, a well-known inhibitor of the mitochondrial ATP synthase, had the same effect as pulsing with ammonium or propionate with, however, much faster kinetics and higher reversibility. Breakdown of the basolateral or apical barrier using the antibiotic nystatin allowed the intracellular pH to be clamped to that of the saline facing the nystatin-treated epithelial border. Cell acidification achieved by this manipulation led to a reduction in both apical I(P) and basolateral P(K). The transepithelial I(K) showed an approximately half-maximal reduction at external pH values close to 5 in intact tissues, and a similar reduction in I(P) and P(K) values was seen at an intracellular pH of 5 in nystatin-permeabilised epithelia. Thus, the hypothesized V(1)V(o) stabilization by cell acidity is not reflected in the pH-sensitivity of I(P). Moreover, all components that transport K(+) are synchronously inhibited below pH 6. The significance of our findings for the midgut in vivo is discussed.
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PMID:Insect midgut K(+) secretion: concerted run-down of apical/basolateral transporters with extra-/intracellular acidity. 1189 60

Net proton secretion and unidirectional chloride fluxes were measured in isolated skin of toads ( Bufo bufo) and frogs ( Rana esculenta) mounted in an Ussing chamber and exposed to a Ringer's solution on the serosal side and a freshwater-like solution (1-3 mM Cl(-)) on the external side. Active proton secretion was 34.2+/-2.0 pmol.cm(-2).s(-1) ( n=18) in frog skin, and 16.7+/-1.7 pmol.cm(-2).s(-1) ( n=10) in toad skin. Proton secretion by toad skin was dependent on the transepithelial potential ( V(T)), and an amiloride-insensitive short-circuit current was stimulated by exogenous CO(2)/HCO(3)(-), indicating the presence of a rheogenic proton pump. Cl(-) influx was 37.4+/-7.5 pmol.cm(-2).s(-1) ( n=14) in frog skin and 19.5+/-3.5 pmol.cm(-2).s(-1) ( n=11) in toad skin. In toad skin, the mean Cl(-) flux ratio was larger than expected for simple electro-diffusion. In 8 of 11 sets of paired skins, influx was greater than the efflux indicating active uptake of Cl(-). Cl(-) influx in toad skin was unaffected by large perturbations (100-150 mV) of V(T), which was accomplished by adding amiloride to the outer bath under open circuit conditions. A component of the Cl(-) efflux seemed to be dependent on V(T). 4,4'-Diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS; 0.3 mM or 1.3 mM) inhibited Cl(-) influx and, surprisingly, increased Cl(-) efflux in toad skin. Influx and efflux of Cl(-) in toad skin were highly dependent on the external [Cl(-)] in the freshwater range (0.1-4 mM). (36)Cl(-) influx decreased whereas the total Cl(-) efflux increased as a function of external [Cl(-)]. These data indicate the presence of a DIDS-sensitive, electroneutral carrier mechanism with an external binding site for Cl(-). Ethoxzolamide (100 micro M), an inhibitor of carbonic anhydrase, reduced proton secretion and Cl(-) influx in frog skin. Concanamycin A (0.1-10 micro M), a specific vacuolar-type proton pump (V-ATPase) inhibitor, significantly reduced proton secretion in frog skin. In addition, concanamycin A (1 micro M) significantly reduced Cl(-) influx in frog skin. We suggest that the active proton secretion and Cl(-) influx are coupled. We hypothesise that an apical V-ATPase is capable of energising active Cl(-) uptake in fresh water by creating a favourable gradient for an apical HCO(3)(-) exit in exchange for external Cl(-). The data also suggest that a carbonic anhydrase activity provides H(+) and HCO(3)(-) for apically co-expressed proton pumps and Cl(-)/HCO(3)(-) exchangers.
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PMID:Proton pump activity is required for active uptake of chloride in isolated amphibian skin exposed to freshwater. 1219 12

IL-1beta is suspected to be involved in the diarrhea that always accompanies inflammatory bowel disease. This work was aimed at studying the in vivo effect of IL-1beta on the net absorption of fluid, Na(+) and Cl(-) from the rat colon, and at delineating its mechanism of action. Rats were injected i.p. with IL-1beta (1 mug/kg body weight) and the colon was perfused, four hours later, with Krebs-Ringer buffer. Net fluid absorption was calculated as the difference between the total volume of the buffer infused and collected per cm(2) of perfused intestine. Chloride in both buffers was determined by titration according to Mohr's method and net Cl- absorption was calculated in the same way. IL-1beta reduced the net absorption of water and chloride. The cytokine also reduced the percentage recovery of the Na(+)-K(+) ATPase activity in crude homogenates of membranes from surface and crypt colonic cells as revealed by the determination of inorganic phosphate released. In addition IL-1beta decreased the protein expression of the Na(+)-K(+) pump and increased that of the NaKCl(2) symporter. It is concluded that IL-1beta has a dual effect: it inhibits the Na(+)-K(+) pump and consequently NaCl absorption, and up-regulates the NaKCl(2) transporter and increases Cl(-) secretion. The ultimate effect of the two processes is a net decrease in Na(+)+ and Cl(-) absorption and an increase in water retention in the colon leading to the observed diarrhea in inflammatory bowel disease.
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PMID:The mechanism by which interleukin-1 beta reduces net fluid absorption from the rat colon. 1223 80

Recent studies provided evidence that the ruminal epithelium is able to absorb D-glucose even at physiologically low intraruminal concentrations. To elucidate whether ruminal D-glucose transport shows adaptive responses during food deprivation, transport of 3-0-methyl-alpha-D-glucose (3-OMG), a hardly metabolizable D-glucose analogue, was measured in isolated ruminal epithelia obtained from hay-fed or food-deprived adult sheep. In both groups, a significant net absorption of 3-OMG to the serosal side (in vivo: blood side oriented) could be detected at 3-OMG concentrations between 0.25 mM and 5 mM. Net absorption of 3-OMG was abolished by mucosal (in vivo: lumen side oriented) addition of phlorizin, an inhibitor of the sodium glucose-linked transporter 1 (SGLT-1). Net absorption of 3-OMG followed Michaelis-Menten kinetics, but apparent affinity and maximal transport capacity were lower in epithelia obtained from food-deprived sheep. In contrast to the decrease of the (secondary) active 3-OMG transport, serosal-to-mucosal permeation of 3-OMG increased after food deprivation, suggesting an elevated passive 3-OMG transfer. It is concluded that the altered transport characteristics are either part of a global energy-sparing process during food deprivation (i.e., a lowered activity of the Na+/K+-ATPase) or result from specific down-regulation of SGLT-1.
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PMID:Influence of food deprivation on the transport of 3-O-methyl-alpha-D-glucose across the isolated ruminal epithelium of sheep. 1241 97

Land crabs produce isosmotic urine but reduce salt loss by reabsorbing salt via the gills to produce a dilute excretory fluid (P). This branchial salt reclamation is regulated in response to changes in dietary salt availability. The regulation of branchial Na reabsorption and osmotic status was investigated in the terrestrial crab Gecarcoidea natalis on Christmas Island. Confinement within field enclosures had no general effect on salt and water balance compared with crabs free in the rainforest but there were seasonal effects. Extracellular fluid volume was 27.9% body mass during the wet season but only 22.7% in the dry season. Urine production was 53 ml kg(-1) day(-1) in the dry season but 111 ml kg(-1) day(-1) in the wet season, while water flux rates were 140 ml kg(-1) day(-1) and 280 ml kg(-1) day(-1), respectively. Serotonin but not dopamine increased urine production by at least 16% but only during the dry season when rates were seasonally lowered. Crabs acclimated to drinking 50% seawater increased haemolymph osmotic pressure and downregulated branchial reabsorption of salt. Net Na flux (J(net)) and unidirectional Na influx (J(in)) were investigated in branchial perfusion experiments. In red crabs acclimated to drinking freshwater, J(in), J(net) and the activity of the Na(+)/K(+)-ATPase were increased by serotonin, indicating that the increase of sodium absorption was due to a stimulation of the ATPase. Red crabs drinking 50% seawater reduced J(net) primarily due to increased passive loss (J(out)), since both J(in) and Na(+)/K(+)-ATPase were unchanged. Serotonin and dopamine abolished the increased diffusive loss and re-established J(net) with no change in J(in). G. natalis exhibits different regulatory systems. Branchial salt uptake can be adjusted via the leak component when adequate salt is available but also by stimulated active uptake under diluting conditions. The gills are important sites of ion pumping in euryhaline aquatic crabs, and the upregulation of J(net) in red crabs is reminiscent of that in marine crabs. Serotonergic stimulation of branchial uptake, independent of cAMP, and hormonally modulated ion leakage are presently unique to terrestrial species.
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PMID:Regulation of urine reprocessing in the maintenance of sodium and water balance in the terrestrial Christmas Island red crab Gecarcoidea natalis investigated under field conditions. 1284 30

Renal tubular transport and its regulation are reviewed for Na(+) (and Cl(-)), and for fluid and organic anions (including urate). Filtered Na(+) (and Cl(-)) is reabsorbed along the tubules but only in mammals and birds does most reabsorption occur in the proximal tubules. Reabsorption involves active transport of Na(+) and passive reabsorption of Cl(-). The active Na(+) step always involves Na-K-ATPase at the basolateral membrane, but the entry step at luminal membrane varies among tubule segments and among vertebrate classes (except for Na(+)-2Cl(-)-K(+) cotransporter in diluting segment). Regulation can involve intrinsic, neural and endocrine factors. Proximal tubule fluid reabsorption is dependent on Na(+) reabsorption in all vertebrates studied, except ophidian reptiles. Fluid secretion occurs in glomerular and aglomerular fishes, reptiles and even mammals, but its significance is not always clear. A non-specific transport system for net secretion of organic anions (OAs) exists in the proximal renal tubules of almost all vertebrates. Net transepithelial secretion involves: (1) transport into the cells at the basolateral side against an electrochemical gradient by a tertiary active transport process, in which the final step involves OA/alpha-ketoglutarate exchange and (2) movement out of the cells across the luminal membrane down an electrochemical gradient by unknown carrier-mediated process(es). Regulation may involve protein kinase C and mitogen-activated protein kinase. Urate is net secreted in the proximal tubules of birds and reptiles. This process is urate-specific in reptiles but in birds, it may involve both a urate-specific system and the general OA system.
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PMID:Regulation of renal proximal and distal tubule transport: sodium, chloride and organic anions. 1461 78

Periophthalmodon schlosseri is an amphibious and obligatory air-breathing teleost, which is extremely tolerant to environmental ammonia. It actively excretes NH(4)(+) in ammonia loading conditions. For such a mechanism to operate efficaciously the fish must be able to prevent back flux of NH(3). P. schlosseri could lower the pH of 50 volumes (w/v) of 50% seawater in an artificial burrow from pH 8.2 to pH 7.4 in 1 day, and established an ambient ammonia concentration of 10 mmol l(-1) in 8 days. It could alter the rate of titratable acid efflux in response to ambient pH. The rate of net acid efflux (H(+) excretion) in P. schlosseri was pH-dependent, increasing in the order pH 6.0<7.0<8.0<8.5. Net acid flux in neutral or alkaline pH conditions was partially inhibited by bafilomycin, indicating the possible involvement of a V-type H(+)-ATPase. P. schlosseri could also increase the rate of H(+) excretion in response to the presence of ammonia in a neutral (pH 7.0) external medium. Increased H(+) excretion in P. schlosseri occurred in the head region where active excretion of NH(4)(+) took place. This would result in high concentrations of H(+) in the boundary water layer and prevent the dissociation of NH(4)(+), thus preventing a back flux of NH(3) through the branchial epithelia. P. schlosseri probably developed such an 'environmental ammonia detoxification' capability because of its unique behavior of burrow building in the mudflats and living therein in a limited volume of water. In addition, the skin of P. schlosseri had low permeability to NH(3). Using an Ussing-type apparatus with 10 mmol l(-1) NH(4)Cl and a 1 unit pH gradient (pH 8.0 to 7.0), the skin supported only a very small flux of NH(3) (0.0095 micromol cm(-2) min(-1)). Cholesterol content (4.5 micromol g(-1)) in the skin was high, which suggests low membrane fluidity. Phosphatidylcholine, which has a stabilizing effect on membranes, constituted almost 50% of the skin phospholipids, with phosphatidyleserine and phsophatidylethanolamine contributing only 13% and 15%, respectively. More importantly, P. schlosseri increased the cholesterol level (to 5.5 micromol g(-1)) and altered the fatty acid composition (increased total saturated fatty acid content) in its skin lipid after exposure to ammonia (30 mmol l(-1) at pH 7.0) for 6 days. These changes might lead to an even lower permeability to NH(3) in the skin, and reduced back diffusion of the actively excreted NH(4)(+) as NH(3) or the net influx of exogenous NH(3), under such conditions.
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PMID:The giant mudskipper Periophthalmodon schlosseri facilitates active NH(4)(+) excretion by increasing acid excretion and decreasing NH(3) permeability in the skin. 1474 11

The current models for branchial acid excretion in fishes include Na(+)/H(+) exchange and the electrogenic excretion of H+ via H+-ATPase. The predominant route of acid excretion in some freshwater fishes is thought to be via the H+-ATPase/Na+ channel system. The euryhaline Fundulus heteroclitus may not fit this profile even when adapted to freshwater (FW). We hypothesize that the Na+/H+ exchanger (NHE) in this species may play a predominant role in acid-base regulation for both marine and FW adapted animals. Acidosis induced by ambient hypercapnia (1% CO2 in air), resulted in an increase in net H+ excretion to the water in F. heteroclitus pre-adapted to FW, brackish (isoosmotic; BW) and seawater (SW). Both FW and SW adapted mummichogs were tested for NHE protein expression using mammalian NHE antibodies, and we identified NHE-like immunoreactive proteins in gill membrane preparations from both groups. Hypercapnia induced a approximately three-fold elevation in gill NHE2-like protein in FW animals but SW adapted fish showed inconsistent NHE3-like protein expression. There was no change in NHE-1 levels in FW fish. In contrast, SW animals demonstrated a significant increase in both NHE1 and NHE3-like proteins following hypercapnia but limited expression of the NHE2 protein. We hypothesize that different isoforms of NHE may be preferentially expressed depending on the salinity to which the animals are adapted. Net H+ transfers during acidosis may be driven, at least in part by the action of these transporters.
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PMID:The effect of environmental hypercapnia and salinity on the expression of NHE-like isoforms in the gills of a euryhaline fish (Fundulus heteroclitus). 1588 Jul 78

This work investigated the effect of different doses of PGE2 on net water and Cl- absorption from the rat colon, using an in situ perfusion technique. PGE2 exerted opposite effects at different concentrations. Net water and Cl- absorption was significantly reduced at low doses with a minimum at 0.4 microg/100g BW, and significantly elevated at high doses with an observed maximal effect at 21 microg/100g BW. At low doses, PGE2 increased in superficial cells, the activity of the Na+-K+ ATPase and the protein expression of the Na+K+2Cl- cotransporter, but reduced them in crypt cells. Thus, the reduction in net water and Cl- absorption was ascribed to an increase in secretion by surface cells that masked absorptive processes. At high doses, PGE2 increased significantly the activity of the Na+-K+ ATPase in superficial cells only, and was without any effect on the protein expression of the cotransporter and the pump in both surface and crypt cells. The observed increase in net water and Cl- absorption was attributed in this case to an increase in absorptive processes with no effect on secretion.
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PMID:PGE2 exerts dose-dependent opposite effects on net water and chloride absorption from the rat colon. 1651 9


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