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 response of the intracellular pH (pHi, measured with BCECF) of the caecal and distal colonic epithelium of guinea pig and of monolayers of HT29 clone 19a cells on the addition of short-chain fatty acids (SCFA) was assessed. Addition of SCFA to the luminal side of these cells had no major effect on pHi, independent of whether the apical Na+/H+ exchange or the apical K+/H+ ATPase was inhibited or not. Addition of SCFA to the serosal side, on the other hand, caused a marked decrease of pHi, followed by an effective regulation back to basal values, and after removal of the acid, the cells became alkalinized. Intracellular pH is mainly regulated by mechanisms in the basolateral membrane. The basolateral Na+/H+ exchanger and the Cl-/HCO3- exchanger were mainly responsible for pHi regulation. Inhibition studies are consistent with a NHE-1 type Na+/H+ exchanger in the basolateral membranes. The apical Na+/H+ exchanger of caecal enterocytes and in HT29 cells, and the apical K+/H+ ATPase in the apical membrane of the distal colon have no or little influence on pHi regulation. The comparison shows that the HT29-19a cell line is an adequate model for studying pHi phenomena of hind gut epithelial cells.
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PMID:Effect of SCFA on intracellular pH and intracellular pH regulation of guinea-pig caecal and colonic enterocytes and of HT29-19a monolayers. 936 78

In the rapidly increasing elderly population, diarrhoea as a result of drug therapy is an important consideration. The elderly consume a disproportionately large number of drugs for multiple acute and chronic diseases. Drugs can compromise both immune and nonimmune responses. Aging decreases the quality and proportion of T cells which in turn reduces the production of secretory IgA, the primary immune response of the gut. Acid production in the stomach decreases with increasing age and this compromise its vital 'self-sterilising' function, thus increasing the risk of diarrhoea due to viral, bacterial and protozoal pathogens. Other nonimmune defence mechanisms include the motility of the small intestine and the host-protective commensal bacteria of the colon. Drug induced hypomotility may result in bacterial overgrowth, deconjugation of bile salts and diarrhoea. Less commonly, diarrhoea may occur due to hypermotility because of a cholinergic-like syndrome. In the colon the host-protective commensal bacteria provide a powerful defence against pathogens. Disruption of this commensal population by antibiotic therapy may result in Clostridium difficile supra-infection which causes diarrhoea through toxin production. This is especially important in the elderly patient on chemotherapy for malignancy and those with multiple diseases. The organism responds to vancomycin, metronidazole and bacitracin. Metronidazole is the suggested drug of choice, with vancomycin reserved for relapses. Drugs also cause diarrhoea by interfering with normal physiological processes. Drugs impair fluid absorption by activating adenylate cyclase within the small intestinal enterocyte which increases the level of cyclic AMP. This causes active secretion of Cl- and HCO3-, passive efflux of Na+, K+ and water and inhibition of Na+ and Cl- into the enterocyte. Examples of these drugs (secretagogues) are bisacodyl, misoprostol and chenodeoxycholic acid (used to dissolve cholesterol gallstones). Drugs may also affect a second mechanism that regulates water and electrolyte transport, the Na+, K+ exchange pump. The energy for this pump is provided by the ATPase mediated breakdown of ATP. ATPase may be inhibited by digoxin, auranofin, colchicine and olsalazine. A number of drugs cause osmotic diarrhoea including antacids containing magnesium trisilicate or hydroxide. Lactulose is being used increasingly in compensated liver disease to increase protein tolerance and prevent hepatic encephalopathy. Sorbitol, an osmotic laxative agent also used in some liquid pharmaceutical preparations, induces diarrhoea by virtue of its osmotic potential. Another mechanism by which drugs cause diarrhoea is by mucosal damage of the small and large bowel. In the small intestine mucosal damage causes diarrhoea and fat malabsorption, as may occur with neomycin and colchicine. In the colon, for example, gold salts and penicillamine cause colitis of varying severity. Though the causes of diarrhoea are diverse, a drug-associated aetiology should always be considered and actively sought and addressed to prevent the complications of dehydration, electrolyte imbalance and undernutrition.
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PMID:Mechanisms of drug-induced diarrhoea in the elderly. 978 28

The metabolism of Cu is intimately linked with its nutrition. From gut to enzymes, Cu bioavailability to key enzymes and other components operates through a complex mechanism that uses transport proteins as well as small molecular weight ligands. Steps in Cu transport through the blood, absorption by cells, and incorporation into enzymes are slowly being understood. Cloning and sequencing of the genes for Menkes disease and Wilson disease has shown that membrane-bound enzymes analogous to Cu-ATPases in prokaryotes are equally important to Cu transport and homeostasis in mammalian cells. The primary structure of the mammalian Cu-ATPases has been deduced from cDNAs from tissues and organs. It now appears that mammalian Cu-ATPase have tissue and developmental specificity. In this review, we will focus on the Cu-ATPase that has been identified with Menkes disease. An emphasis will be placed on the existence of multiple forms of the ATPase and some indication as to how the different isoforms befit their role in the normal physiology of copper, specifically transmembrane transport and maintenance of a favorable internal cellular environment.
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PMID:Genes regulating copper metabolism. 982 11

Lepidopteran larvae demonstrate several remarkable specialisations of the alimentary canal: the most active epithelial transport known; a unique cell type, called a goblet cell; and the highest pH values known to be generated by a biological system. The electrogenic K+ pump in midgut is now known to be energised by a H+-pumping V-ATPase, and net alkali metal transport is achieved by linking it to a nH+/alkali metal exchanger, which recycles H+ into the cytoplasm. Generation of high luminal pH is modelled as a passive (Nernstian) distribution of protons in the electrical field generated by the V-type ATPase. Electrode impalements show that the potential difference across the goblet cavity membrane is extremely high. Measurements of pH gradients generated in vitro confirm that the midgut itself generates such a gradient, that this process relies on metabolic energy, and that the differential ability of midgut subregions to perform acid-base transport maps to their differing morphologies and to the pH profiles observed along the gut in vivo. During larval/larval moults, K+ transport is suppressed. The transepithelial potential difference (PD) across the gut collapses and recovers in phase with the loss and recovery of the gut pH gradient, and with tissue V-ATPase activity, confirming that these processes are intimately linked. Acridine Orange partitions into acidic compartments and might be expected to be concentrated in goblet cavities, as these are the compartments toward which the V-ATPase pumps protons. However, under normal conditions, Acridine Orange is excluded from the cavities. Red metachromasia of the cavities (implying low pH) is only observed when the ion transport status of the tissue is compromised. It thus seems likely that, under physiological conditions, K+/H+ exchange is tight enough to produce a neutral or alkaline, rather than acidic, cavity. Molecular analysis of the 16 000 Mr subunit from Manduca midgut reveals it to be closely similar to other known 16 000 Mr sequences, particularly that from Drosophila brain. It is thus likely to be a true H+ channel, rather than one modified for K+ transport. The cavity can be modelled in two ways: (i) to isolate the site of proton equilibration electrically from the main gut lumen, and thus allow larger pH gradients to develop, or (ii) to buffer the V-ATPase from the alkaline pH in the gut lumen, which would otherwise destroy the gradient driving the exchange of H+ for alkali metal cations. The first model would predict a high cavity pH, whereas the second would predict a near neutral pH and would imply a non-cavity route for transport of base equivalents. Work with both pH-sensitive dyes and pH-sensitive electrodes so far tends to support the second model.
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PMID:pH GRADIENTS IN LEPIDOPTERAN MIDGUT. 987 48

The midgut plasma membrane V-ATPase from larval Manduca sexta, the tobacco hornworm, is the sole energizer of any epithelial ion transport in this tissue and is responsible for the alkalinization of the gut lumen up to a pH of more than 11. This mini-review deals with those topics of research on this enzyme which may have contributed or are expected to contribute novel and general aspects to the field of V-ATPases. Topics dealt with include novel subunits or the quaternary structure of the V1 complex, as well as the regulation of the enzyme's function by reversible dissociation of the V1 from the V0 complexes and by genetic control on the transcriptional and posttranscriptional level.
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PMID:The plasma membrane H+-V-ATPase from tobacco hornworm midgut. 1034 Aug 50

The pH profile, gross structure, ultrastructure and immunolabeling of the mosquito (Aedes aegypti) larval midgut are described as a first step in analyzing the role of plasma membrane H(+ )V-ATPase in the alkalization of the gut, nutrient uptake and ionic regulation. Binding of an antibody to H(+ )V-ATPase subunit E colocalizes with 'portasomes' (approximately 10 nm in diameter), which are thought to correspond to the V(1) part of the H(+) V-ATPase. In gastric caeca (pH 8), both antibody-binding sites and portasomes are located apically; in the anterior midgut (pH 10-11), they are located basally; and in the posterior midgut (pH approximately equal to 8) they are again located apically. The hypothesis that the energization of alkalization is mediated by an H(+) V-ATPase is supported by the inability of larvae to maintain the high pH after 72 h in 10 (micro)M bafilomycin B1. Confirming earlier reports, the two principal epithelial cell types are designated as 'columnar' and 'cuboidal' cells. The apical plasma membranes (microvilli) of epithelial cells in the gastric caeca and basal infoldings of anterior midgut are invaded by mitochondria that lie within approximately 20 nm of the portasome-studded plasma membranes. The colocalization of V-ATPase-immunolabeling sites and portasomes to specific plasma membranes within so-called 'mitochondria-rich' cells of gastric caeca and anterior midgut suggests that midgut alkalization in mosquitoes is achieved by molecular mechanisms similar to those that have been described in caterpillars, even though the gross structure of the midgut and the localization of the V-ATPase are dissimilar in the two species. In caterpillars, the high alkalinity is thought to break down dietary tannins, which block nutrient absorption; it may play a similar role in plant-detritus-feeding mosquito larvae. The colocalization of immunolabeling sites and portasomes, together with the presence of long, 'absorptive-type' microvilli in the posterior midgut, suggest that the V-ATPase energizes nutrient uptake there.
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PMID:Antibody to H(+) V-ATPase subunit E colocalizes with portasomes in alkaline larval midgut of a freshwater mosquito (Aedes aegypti). 1046 Jul 32

Attachment of Salmonella typhimurium to epithelial surfaces elicit significant alterations in different cell signalling events which lead to the development of disease. The present investigation was conducted to evaluate the effect of immunization of rats with porins, on gut physiologic markers following challenge with S. typhimurium. Male albino Wistar rats were immunized with purified porins and challenged by intragastric infection with S. typhimurium. Electrolyte transport, levels of different second messengers and inflammatory mediators were studied. A net absorption of transepithelial fluxes of Na+ and Cl- in immunized-challenged group and secretion in infected group was found. Ca2+ and 3-O-methyl-D-glucose fluxes did not show any change. Significant increase in the levels of [Ca2+]i, cAMP, membrane form of protein kinase C, prostaglandins, NADPH oxidase, Glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, total oxygen free radicals, reactive nitrogen intermediates, citrulline and lipid peroxidation was found in the infected group. However, in the immunized-challenged group, the values of all the parameters were found to be almost the same as that of control as well as immunized groups. Na+, K+-ATPase and calmodulin levels were unaltered in all the groups of animals. The results of this study thus suggest that immunization of rats with purified Salmonella porins followed by subsequent challenge with the organism might be helpful for the prevention of multiple physiologic derangements in isolated ileal cells.
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PMID:The effect of immunization with porins on gut pathophysiological response in rats infected with Salmonella typhimurium. 1063 Jun 36

In vitro and in vivo experiments with perfusion in 20- and 60-day old rats revealed that K+ absorption in the gut as well as 86Rb uptake in the distal colon was significantly higher in younger rats due probable, to the higher activity of the apex-located K+-dependent ATPase and lower activity of the basolateral K+-carriers. The luminal blockade of K+ absorbing pumps with ouabain or omeprazole resulted in a decrease of the K+ absorption and K2 accumulation in skeletal muscles. The higher K+-absorbing/K_ secreting mechanisms ratio in younger rats contributes to the positive potassium balance.
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PMID:[Age characteristics of K(+) transport in the rat distal colon]. 1074 Aug 41

We used 28 crossbred wether lambs to determine the effects of dietary forage:concentrate ratio and metabolizable energy intake on visceral organ growth and oxidative capacity of gut tissues in lambs. Lambs were assigned randomly to a factorial arrangement of dietary treatments consisting of pelleted diets containing either 75% orchardgrass or 75% concentrate fed once daily at either .099 or .181 Mcal ME x (kg BW(.75))(-1) x d(-1). After a 52-d feeding period, lambs were slaughtered to obtain measurements of visceral organ mass and composition and oxidative capacity of isolated epithelial cells. Lamb performance, as measured by DMI, ADG, and efficiency of gain, was greater (P = .0001) for both diets at high ME intake. Likewise, lambs fed 75% concentrate gained faster and more (P < or = .01) efficiently than lambs fed 75% forage. Total digestive tract (TDT; includes rumen, reticulum, omasum, abomasum, and intestines) weight increased (P = .0001) with ME intake and was greater (P = .03) in lambs fed 75% forage than in those fed 75% concentrate. As a percentage of empty body weight (EBW), TDT weight increased with ME intake in lambs fed 75% forage, but it was unaffected by ME intake in lambs fed 75% concentrate (diet x intake, P = .03). Liver weight increased (P = .0001) with ME intake and was greater (P = .005) in lambs fed 75% concentrate vs 75% forage; however, liver weight as a percentage of EBW was increased (P = .0002) with ME intake but was unaffected by diet. Greater ME intake increased (P < or = .02) small intestinal (SI) epithelial and muscle mass of 15-cm sections, whereas jejunal epithelial mass was greater (P = .01) for lambs fed 75% forage vs 75% concentrate. Rumen epithelial concentrations of DNA and RNA increased (P < or = .02) with greater ME intake, whereas SI concentrations of DNA and RNA were largely unaffected by diet or ME intake. The activity of Na(+)-K(+)-ATPase increased in ileal epithelium (P < or = .02) with ME intake and concentrate in the diet, but activity in ruminal epithelium increased (P = .05) with concentrate. Total oxygen consumption by isolated ruminal and intestinal epithelial cells was unaffected by treatment. These data suggest that ME intake and level of dietary forage affect ruminal and intestinal growth via changes in cellular hyperplasia. Additionally, this study supports the concept that ME intake and diet composition alter gut energy expenditure, at least in part, through changes in mass rather than mass specific metabolism.
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PMID:Effects of diet forage:concentrate ratio and metabolizable energy intake on visceral organ growth and in vitro oxidative capacity of gut tissues in sheep. 1076 85

In mammals, copper (Cu) absorption occurs mostly in the small intestine, and some of the Cu transporters involved in its uptake have been characterised. In fish, however, the regions of the gut involved in Cu absorption and the membrane transport mechanisms responsible for gastrointestinal Cu uptake are unknown. Everted gut sacs and isolated perfused intestine of Clarias gariepinus were used to explore Cu absorption (at 22 degrees C). Gut sacs exposed to 100 micromol l(-1) mucosal solution Cu ([Cu](m)) showed that Cu was mostly (70 %) absorbed in the middle and hind intestine. Most of the accumulated Cu was located in the mucosa. In perfused intestines, cumulative Cu absorption from the mucosal solution to the serosal perfusate was greatest at 10 micromol l(-1) [Cu](m) and decreased at higher values of [Cu](m), while tissue accumulation of Cu showed a dose-dependent elevation. Absorption efficiency therefore declined with increasing Cu dose, and basolateral transport was the limiting factor in Cu uptake. Serosal applications of the P-type ATPase inhibitor vanadate (100 micromol l(-1)) or the anion transport inhibitor DIDS (100 micromol l(-1)) caused threefold increases in net Cu uptake (at [Cu](m)=10 micromol l(-1)). The vanadate effect was explained by a reduction in transepithelial potential rather than inhibition of Cu-ATPase, but the DIDS effect was not. Transepithelial potential, water transport and tissue [Cu] were not affected by DIDS, but tissue [K(+)] was elevated. Removal of Cl(-) simultaneously from both the mucosal and serosal solutions caused a 10-fold reduction in the rate of Cu uptake, while removal of Cl(-) from the mucosal solution only completely abolished Cu absorption to the serosal perfusate. Transepithelial potential effects are discussed. We conclude that Cu absorption occurs mostly in the intestine and is normally driven by a basolateral Cu/anion symport that prefers Cl(-).
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PMID:Mechanisms of gastrointestinal copper absorption in the African walking catfish: copper dose-effects and a novel anion-dependent pathway in the intestine. 1088 75


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