Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mucosal Na,K-ATPase activity was studied in rectal biopsy specimens from 19 children with ulcerative colitis (UC) (mean age, 13 years) and 4 children with Crohn's colitis (mean age, 14 years) and compared with biopsy specimens from 12 control children (mean age, 12 years). The Na,K-ATPase activity was significantly decreased in UC with severe rectal inflammation compared with UC in remission or with children with unspecific symptoms and normal mucosa (p less than 0.001, respectively). A higher enzyme activity was shown with age in the group with normal rectal mucosa and no evidence of inflammatory bowel disease (n = 17). The decreased Na,K-ATPase in UC with severe rectal inflammation might contribute to the diarrhoea by impairment of sodium transport.
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PMID:Na,K-ATPase activity in rectal mucosa of children with ulcerative colitis and Crohn's disease. 255 82

In inflammatory bowel disease (IBD), mucosal damage and loss of colonic function are regarded as major consequences of inflammation. Decreased colonic (Na+ + K+)-ATPase activities with diminished reabsorption of sodium and water have been found in active stages of ulcerative colitis. In this study, we report an inverse relationship between colonic (Na+ + K+)-ATPase activity and the degree of mucosal inflammation in 19 patients with IBD of mild to moderate disease activity. Various macroscopic and histologic types of mucosal lesions were differently associated with the (Na+ + K+)-ATPase activities. 5'-nucleotidase activity was not associated with the degree of mucosal inflammation or the kind of macroscopic or histologic lesions. Our findings support the view that, in contrast to 5H-nucleotidase, (Na+ + K+)-ATPase activity may better reflect the severity of mucosal damage and the degree of inflammation in IBD.
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PMID:Inverse relationship between colonic (Na+ + K+)-ATPase activity and degree of mucosal inflammation in inflammatory bowel disease. 283 38

The effects of lipoxygenase products (5-, 12-, 15-HETE, LTB4) and superoxide radicals on human colonic (Na+ + K+)-ATPase and specific ouabain binding were measured. No significant inhibition in concentrations up to 3 x 10(-5) M was observed. The results are discussed with regard to a possible role of lipoxygenase products and radicals in the pathogenesis of water and electrolyte disturbances in various diarrheal states including inflammatory bowel disease.
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PMID:Human colonic (Na+ + K+)-ATPase and specific ouabain binding are not influenced by lipoxygenase products or superoxide radicals. 285 Apr 5

The sodium pump, (Na+ + K+)-ATPase, which is involved in the transport of cations and water movement by the colonic mucosa, may be decreased in various diarrhoeal states. In this study, we have measured 3H-ouabain binding and (Na+ + K+)-ATPase activity in human colonic biopsy homogenates and the influence of various inflammatory and antiinflammatory compounds on these parameters. 3H-ouabain binds to one site of high affinity (KD 1.9 +/- 0.2 X 10(-9) mol/l) with a maximal binding capacity of 7.5 +/- 0.8 X 10(14) binding sites/g protein. Both arachidonic and linoleic acid inhibited (Na+ + K+)-ATPase activity (IC50 arachidonic acid: 7.5 X 10(-5) mol/l, linoleic acid: 6.5 X 10(-5) mol/l) and Mg2+-ATPase activity (IC50 arachidonic acid: 9 X 10(-5) mol/l, linoleic acid: 4 X 10(-5) mol/l). Arachidonic acid inhibited 3H-ouabain binding, (IC50 3.2 X 10(-5) mol/l). The following antiinflammatory compounds, at concentrations up to 1 X 10(-3) mol/l, did not influence ATPase activity directly nor reverse the arachidonic acid-induced inhibition: indomethacin (cyclooxygenase inhibitor), nordihydroguaiaretic acid (lipoxygenase inhibitor), sulphasalazine and its metabolites: 5-aminosalicylic acid, N-acetylaminosalicylic acid and sulphapyridine. These results indicate that human colonic (Na+ + K+)-ATPase is inhibited by the prostanoid precursors, arachidonic and linoleic acid. From a therapeutic point of view (effect on colonic (Na+ + K+)-ATPase and perhaps diarrhoea), the suppression of the production of these prostanoid precursors by drugs may, therefore, be beneficial in the treatment of inflammatory bowel disease.
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PMID:Inhibition of human colonic (Na+ + K+)-ATPase by arachidonic and linoleic acid. 301 58

HLA-DR-positive histiocytes in the lamina propria of the human intestine have been characterised using combined histochemical and immunohistological techniques. In the small intestine, 80-90% of the HLA-DR+ histiocytes had irregular surfaces with stellate processes, and exhibited strong membrane adenosine triphosphatase (ATPase) activity, but weak acid phosphatase (ACP) and non-specific esterase (NSE) activities (HLA-DR+ ACP+/- NSA+/- ATP++; type 1 cell). In contrast, in the lamina propria of the colon the majority (60-70%) of HLA-DR+ cells were large, round cells with strong ACP and NSE activities but no detectable ATPase activity (HLA-DR+ ACP++ NSE++ ATP+/-; type 2 cell). The colon also contained a population of type 1 cells (30-40%). In active inflammatory bowel disease affecting the colon a third population of HLA-DR+ histiocytes was seen. These cells were irregular in outline, with many processes, and were ACP++ NSE+ ATP+/- (type 3 cell). The type 3 cells appeared to replace type 2 cells. After treatment, the appearances returned to normal. These findings suggest that the different populations of HLA-DR+ histiocytes in the human intestine may have several functions, reflecting the different forms of antigen present in the intestine. The alterations in inflammatory bowel disease may represent activation in response to an invading antigen.
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PMID:Heterogeneity of HLA-DR-positive histiocytes in human intestinal lamina propria: a combined histochemical and immunohistological analysis. 633 64

Olsalazine (azodisalicylate) and mesalazine (5-aminosalicylic acid) have recently been developed as new treatment modalities for inflammatory bowel disease to avoid sulfasalazine-related side effects. However, there are reports regarding new and hitherto unexpected side effects in some patients receiving olsalazine or mesalazine, such as watery diarrhea. Since sodium pump activities play an important role in the pathogenesis of water and electrolyte disturbances, we investigated the influence of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase and its specific [3H]-ouabain binding. We found a concentration-dependent inhibition of ileal and colonic (Na+ + K+)-ATPase by olsalazine with an IC50 of 4.1 mM and 4.8 mM, respectively. Mesalazine inhibited this enzyme in the ileum with an IC50 of 4.0 mM and in the sigmoid colon with an IC50 3.5 mM. In addition, [3H]-ouabain binding was inhibited by mesalazine with an IC50 of 3.6 mM. The maximal inhibition, however, did not exceed 80% under any conditions (up to 10 mM drug concentration). Olsalazine and mesalazine induce inhibition of the ileal and colonic sodium pump activities that may (in addition to other possible mechanisms) mediate impaired water and electrolyte absorption. This is possibly of clinical relevance in patients with severely damaged mucosa. In patients with milder forms of mucosal inflammation, this inhibition most likely is of minor importance because of the great capacity of the (Na+ + K+)-ATPase and the incomplete inhibition leaving at least 20% of the enzyme activity intact.
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PMID:Effect of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase. A possible diarrhogenic factor? 838 34

The colonic epithelium has both absorptive and secretory functions. The transport is characterized by a net absorption of NaCl, short-chain fatty acids (SCFA), and water, allowing extrusion of a feces with very little water and salt content. In addition, the epithelium does secret mucus, bicarbonate, and KCl. Polarized distribution of transport proteins in both luminal and basolateral membranes enables efficient salt transport in both directions, probably even within an individual cell. Meanwhile, most of the participating transport proteins have been identified, and their function has been studied in detail. Absorption of NaCl is a rather steady process that is controlled by steroid hormones regulating the expression of epithelial Na(+) channels (ENaC), the Na(+)-K(+)-ATPase, and additional modulating factors such as the serum- and glucocorticoid-regulated kinase SGK. Acute regulation of absorption may occur by a Na(+) feedback mechanism and the cystic fibrosis transmembrane conductance regulator (CFTR). Cl(-) secretion in the adult colon relies on luminal CFTR, which is a cAMP-regulated Cl(-) channel and a regulator of other transport proteins. As a consequence, mutations in CFTR result in both impaired Cl(-) secretion and enhanced Na(+) absorption in the colon of cystic fibrosis (CF) patients. Ca(2+)- and cAMP-activated basolateral K(+) channels support both secretion and absorption of electrolytes and work in concert with additional regulatory proteins, which determine their functional and pharmacological profile. Knowledge of the mechanisms of electrolyte transport in the colon enables the development of new strategies for the treatment of CF and secretory diarrhea. It will also lead to a better understanding of the pathophysiological events during inflammatory bowel disease and development of colonic carcinoma.
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PMID:Electrolyte transport in the mammalian colon: mechanisms and implications for disease. 1177 14

Proteinase-activated receptor (PAR) type 2 (PAR-2) has been shown to mediate ion secretion in cultured epithelial cells and rat jejunum. With the use of a microUssing chamber, we demonstrate the role of PAR-2 for ion transport in native human colonic mucosa obtained from 30 normal individuals and 11 cystic fibrosis (CF) patients. Trypsin induced Cl(-) secretion when added to the basolateral but not luminal side of normal epithelia. Activation of Cl(-) secretion by trypsin was inhibited by indomethacin and was further increased by cAMP in normal tissues but was not present in CF colon, indicating the requirement of luminal CF transmembrane conductance regulator. Effects of trypsin were largely reduced by low Cl(-), by basolateral bumetanide, and in the presence of barium or clotrimazole, but not by tetrodotoxin. Furthermore, trypsin-induced secretion was inhibited by the Ca(2+)-ATPase inhibitor cyclopiazonic acid and in low-Ca(2+) buffer. The effects of trypsin were almost abolished by trypsin inhibitor. Thrombin, an activator of PAR types 1, 3, and 4, had no effects on equivalent short-circuit currents. The presence of PAR-2 in human colon epithelium was confirmed by RT-PCR and additional experiments with PAR-2-activating peptide. PAR-2-mediated intestinal electrolyte secretion by release of mast cell tryptase and potentiation of PAR-2 expression by tumor necrosis factor-alpha may contribute to the hypersecretion observed in inflammatory processes such as chronic inflammatory bowel disease.
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PMID:Activation of ion secretion via proteinase-activated receptor-2 in human colon. 1180 40

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

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. It was considered pertinent to assess the pathway in inflammatory bowel disease (ulcerative colitis and regional ileitis). Since endogenous digoxin can regulate neurotransmitter transport, the pathway and the related cascade were also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. All the patients with inflammatory bowel disease were right-handed/left hemispheric dominant by the dichotic listening test. The following parameters were measured in patients with inflammatory bowel disease and in individuals with differing hemispheric dominance: (1) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (2) tryptophan/tyrosine catabolic patterns; (3) free-radical metabolism; (4) glycoconjugate metabolism; and (5) membrane composition and RBC membrane Na+-K+ ATPase activity. Statistical analysis was done by ANOVA. In patients with inflammatory bowel disease there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. Inflammatory bowel disease is associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to immune activation, defective glycoprotein bowel antigen presentation, and autoimmunity and a schizophreniform psychosis important in its pathogenesis. The biochemical patterns obtained in inflammatory bowel disease is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Inflammatory bowel disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.
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PMID:Hypothalamic digoxin, hemispheric chemical dominance, and inflammatory bowel disease. 1295 41


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