Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1 (IL-1) causes a diuresis and natriuresis in experimental animals. The natriuresis is due, at least in part, to IL-1 stimulation of prostaglandin E2 (PGE2) synthesis by the inner medullary collecting duct (IMCD), with resultant inhibition of Na(+)-K(+)-adenosine triphosphatase activity. It is unknown whether IL-1 affects other signal transduction systems in the IMCDs that regulate nephron sodium and water reabsorption. Furthermore, indirect evidence suggests that IL-1 inhibits sodium and water transport in other nephron segments. Consequently we examined (1) the effect of IL-1 on cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) accumulation by rat IMCD cells and (2) IL-1 stimulation of signal transduction mechanisms throughout the nephron. IL-1 had no affect on cGMP or arginine vasopressin-dependent (AVP-dependent) or isoproterenol-dependent cAMP accumulation in cultured rat IMCD cells. IL-1 increased PGE2 levels in rabbit IMCD, cortical collecting tubule (CCT), and to a lesser extent, medullary thick ascending limb cells, but had no effect on proximal tubule cells. IL-1 also did not alter AVP-dependent cAMP accumulation in the CCT. The failure of IL-1 to reduce AVP responsiveness in the CCT was not due to culture conditions, because AVP-dependent cAMP accumulation in freshly isolated CCT cells was also not affected by the cytokine but was inhibited by exogenous PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-1 regulation of collecting duct prostaglandin E2 and cyclic nucleotide accumulation. 819 73

The relationship between the phospholipase-stimulating and immunosuppressive properties of the riminophenazine anti-mycobacterial agent clofazimine and its experimental analogue, B669, has been investigated in vitro. At concentrations of 0.6 microM and upwards, both riminophenazines, particularly B669, caused dose-related inhibition of mitogen- and alloantigen-stimulated uptake of tritiated thymidine by human mononuclear leucocytes (MNL), while in short-term assays both agents increased the release of lysophosphatidylcholine (LPC) and arachidonic acid from these cells. Arachidonate per se at a concentration of 20 microM did not affect mitogen-activated lymphocyte proliferation, while cyclooxygenase and 5'-lipoxygenase inhibitors, as well as water- and lipid-soluble oxidant-scavengers and anti-oxidant enzymes, failed to protect the cells against the anti-proliferative effects of clofazimine and B669. However, LPC caused dose-related inhibition of lymphocyte proliferation. Moreover, co-incubation of NML with alpha-tocopherol (vitamin E), a lysophospholipid complex-forming agent, or with lysophospholipase, protected the cells against clofazimine and B669, as well as against LPC. Na+, K(+)-adenosine triphosphatase was identified as the primary target of riminophenazine/LPC-mediated inhibition of lymphocyte proliferation. Excessive release of anti-proliferative lysophospholipids during clofazimine or B669 treatment of mitogen- or antigen-activated lymphocytes is the probable biochemical mechanism of the immunosuppressive activity of these agents.
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PMID:Clofazimine and B669 inhibit the proliferative responses and Na+, K(+)-adenosine triphosphatase activity of human lymphocytes by a lysophospholipid-dependent mechanism. 826 51

The structure-toxicity relationship of monoketones, a class of organic solvents widely used in industry, was investigated with respect to their in vitro effects on synaptosomal membrane proteins. The toxic parameters used were Na(+)-K(+)-adenosine triphosphatase (Na(+)-K(+)-ATPase), a well-known marker enzyme often used as a membrane toxicity model, and 3H-dihydroalprenolol (3H-DHA)-labeled beta-adrenergic receptor binding that has been shown to be vulnerable to solvent-induced changes in membrane fluidity. In vitro treatments with 12 kinds of monoketones (carbon chain length from 3-10) dose-dependently inhibited both 3H-DHA binding to mouse synaptosomes and Na(+)-K(+)-ATPase activity. The potency of inhibition (IC50) for both the two parameters was linearly related to n-octanol/water partition coefficient and synaptosome/buffer partition coefficient of the test compounds. Additions of monoketones did not significantly alter the number of 3H-DHA binding sites but markedly decreased their affinity. In each monoketone, the IC50 values for 3H-DHA binding and Na(+)-K(+)-ATPase activity were generally within the same range. The anisotropy of fluorescence probe 1,6-diphenyl-1,3,5-hexatriene-labeled synaptosomal membranes was dose-dependently decreased by the monoketones, implying increased membrane fluidity. These results indicate that increasing lipophilicity of monoketones results in increased solvent penetration of synaptic membrane preparations, leading to conformational changes in membrane structure and increased ability to inhibit both neuroreceptor binding and enzyme activity. The present data confirm the importance of the lipid micro-environment of membranes in maintaining the normal functions of membrane-bound proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structure-toxicity relationship of monoketones: in vitro effects on beta-adrenergic receptor binding and Na(+)-K(+)-ATPase activity in mouse synaptosomes. 827 28

We studied the effect of chronic exposure (6 weeks and 6 months) of mice to drinking (tap) water containing 1.76% (0.06 M) aluminum lactate on some cytochemical properties of the blood-brain barrier (BBB). The plasmalemma-bound enzymatic activities of alkaline phosphatase (AP) and Ca(2+)-activated adenosine triphosphatase (Ca(2+)-ATPase) were studied at the ultrastructural level. Anionic sites were localized with cationized ferritin in a pre-embedding procedure and with cationic colloidal gold in a post-embedding procedure applied to brain samples embedded in Lowicryl K4M. Intravenously injected Evans blue and horseradish peroxidase (HRP) were used for evaluation of the functional state of the BBB. The results indicate that chronic exposure to aluminum does not noticeably affect barrier function of the endothelium of cerebral cortex blood microvessels. Focal leakage of larger than capillary microvessels (presumably arterioles and venules) was observed only in a few areas, such as the basal ganglia and amygdaloid nuclei. The localization of both enzymatic activities (AP and Ca(2+)-ATPase) in microvessels remained essentially unchanged. The localization of anionic sites was also unchanged except on the luminal surface of the endothelium of a few blood microvessels located in areas of the brain where leakage of the injected HRP was noted. In these vessels the injected HRP was often attached to the luminal surface of the endothelial cells, suggesting its increased stickiness. These data, compared with our previous observations on brain microvascular endothelial cells growing in vitro, indicate that cytotoxicity of aluminum is evidently less pronounced in the living organism, presumably due to action of detoxicating and regulatory mechanisms.
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PMID:Ultracytochemical studies of the effects of aluminum on the blood-brain barrier of mice. 828 66

The effects of oral vanadate supplementation on intestinal morphometry and glucose transport were examined in STZ-induced diabetic and age-matched control male Sprague-Dawley rats. Animals received 0.1 mg/ml vanadium pentoxide in their drinking water over 14 days. Vanadate reduced intestinal glucose maximal transport capacity in both diabetic and control animals. In jejunum tissue, this decrease in glucose absorption was a direct consequence of downregulation of the glucose carrier and was not related to changes in mucosal morphometry. In the ileum tissue of control animals, the vanadate-induced decrease in glucose maximal transport capacity occurred in conjunction with an increase in carrier affinity and mucosal morphometric measurements. In the ileum tissue of diabetic animals, the vanadate-induced decrease in glucose maximal transport capacity occurred with a decrease in mucosal morphometric measurements. Na(+)-K(+)-adenosine triphosphatase activity was affected by vanadate only in diabetic animals. These results demonstrate that oral vanadate supplementation results in downregulation of the small intestinal sodium-dependent glucose carrier in both diabetic and nondiabetic rats. Furthermore, the vanadate effect may be occurring at the cellular level.
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PMID:Oral vanadate reduces Na(+)-dependent glucose transport in rat small intestine. 839 10

The in vivo anesthetic activity of monoketones in mice was examined in relation to their hydrophobicity and to the in vivo effects on Na+/K+ -adenosine triphosphatase (Na+/K+ -ATPase) activity and membrane fluidity. Anesthetic potency (AD50) of monoketones was determined; AD50 implys the dose required to anesthetize 50% of the animals from the treated group. The n-octanol/water partition coefficient (P) was used as an index of hydrophobicity. Membrane fluidity was determined by using 1,6-diphenyl-1,3,5-hexatriene (DPH) or 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH as fluorescence probes. Log (1/AD50) was the parabolic function of log P, log ((1/AD50) = -0.167(log P)2 + 0.698 log P - 1.365, and the log P that corresponds to the minimum AD50 was estimated to be 2.09. Brain synaptosomes were prepared from mice that were considered anesthetized with each of the 4 monoketones (1.5-fold AD50), methyl n-propyl, methyl n-amyl, methyl 3-methylhexyl and methyl n-octyl ketone. The Na+/K+ -ATPase activity was inhibited by methyl n-propyl ketone alone, membrane DPH fluidity was decreased by each of the 4 monoketones, and membrane TMA-DPH fluidity was decreased by methyl n-propylketone alone. These results suggest an involvement of the decreased DPH fluidity in monoketone-induced anesthesia.
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PMID:Anesthetic activity of monoketones in mice: relationship to hydrophobicity and in vivo effects on Na+/K+ -ATPase activity and membrane fluidity. 861 59

Little information is available on the structure-central nervous system membrane toxicity relationship of alcohols. The purpose of the present study was to study in vitro influence of alcohols (n = 20) on the activity of the toxic indicator Na+/K(+)-adenosine triphosphatase (Na+/K(+)-ATPase) and acetylcholinesterase (AchE), and membrane fluidity in mouse brain synaptosomes, in terms of the structure-activity relationship. The potency of inhibition for the enzymes (IC50) and the potency of increasing membrane fluidity (IC12.5) were determined experimentally, and n-octanol/water partition coefficient (P) and the steric constant Taft Es are cited from the literature. Regression analysis revealed that log 1/IC50 for Na+/K(+)-ATPase is a function of log P and Taft Es. The situation was true for AchE activity. The results indicate that the hydrophobicity expressed as log P and the steric effect of the alcohols play an important role in inhibiting both enzyme activities. A linear relationship between log 1/IC12.5 for membrane fluidity and log P is shown, indicating a significant effect of the alcohols on membrane fluidity. Based on these results, it is suggested that the alcohols inhibit the Na+/K(+)-ATPase and AchE activity through a direct action on the enzymes and/or through changing the membrane fluidity.
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PMID:In vitro influences of alcohols on mouse synaptosomes, and structure-activity relationships. 866 Jan 39

The authors review the physiological, cellular and molecular aspects of the patterns, mechanisms and signals of the adaptation of intestinal transport of sugars and lipids, especially in response to manipulations of dietary lipid content. In models of intestinal adaptation, nutrient uptake is enhanced by an up- or down-regulation of the maximal rate of carrier-mediated transport or by alterations in the passive permeability properties (Pd) of the intestinal brush border membrane (BBM). The importance of unstirred water layers has been demonstrated. Alterations in the Pd for lipid uptake are due to changes in the lipid content of the BBM, which in turn are associated with alterations in the activity of lipid-metabolizing enzymes in the enterocyte microsomal membrane (EMM), and, therefore, alterations in the lipid composition of the EMM. Lipid uptake is also mediated by at least two proteins in the BBM, the sodium-hydrogen exchangers and the membrane-fatty-acid-binding protein. Alterations in the maximal transport rate for glucose and fructose transporters are associated with variations in the abundance of their transporters (including sodium-dependent glucose transporter, glucose and fructose transporter and fructose transporter) in the basolateral membrane sodium-potassium adenosine triphosphatase, and in the abundance of the messenger RNA of the transporters. Isocaloric changes in dietary lipids, such as switching from a saturated to a polyunsaturated diet, within the range seen in human consumption, leads to major alterations in passive and active transport processes. In a proposed model, changes in dietary lipids stimulate intracellular second messengers, modifying gene expression of the transporter carriers and of the EMM lipid-metabolizing enzymes. Thus, an understanding of the mechanisms of intestinal adaptation lays the groundwork for future studies of dietary manipulations. It may also lead to dietary interventions to prevent unwanted or to enhance desirable intestinal adaptation, thereby preventing disease.
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PMID:Nutrients and intestinal adaptation. 888 71

Porphyrins, in combination with light, offer an alternate approach to the treatment of cancer, in the form of photodynamic therapy (PDT). With a view to locate new porphyrins for use in PDT, we evaluated the ability of a novel water-soluble porphyrin, meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (T4CPP) to induce photodamage in membranes, using rat hepatic microsomes as a model system. Hepatic microsomes treated with T4CPP and exposed to visible light showed significant lipid peroxidation, as assessed by the formation of conjugated dienes, lipid hydroperoxides, and thiobarbituric acid-reactive substances. The peroxidation induced was both time- and concentration-dependent. T4CPP plus light also resulted in the destruction of the microsomal enzymes adenosine triphosphatase and glucose-6-phosphatase. Analysis of the products of peroxidation and selective inhibition by specific inhibitors showed that the oxidative damage induced was mainly due to singlet oxygen and partly due to hydroxyl radical. The porphyrin T4CPP was efficiently labeled with 99mTc. When this 99mTc-labeled porphyrin was injected into a mammary-tumor-bearing rat, it accumulated in the tumor. Our studies suggest that T4CPP, due to its potential to localize in tumors and to induce membrane damage as exemplified by alteration in rat liver microsomes, may have possible applications in this new modality of cancer treatment.
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PMID:Photodynamic effects induced by meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin using rat hepatic microsomes as model membranes. 905 55

Keratinocyte growth factor (KGF) prevents alpha-naphthylthiourea (ANTU)-induced permeability edema ex vivo. To explore the mechanisms in this involved effect, we administered KGF (5 mg/kg, intratracheally) 48 h prior to ANTU (50 mg/kg, intraperitoneally). Several groups were studied: phosphate-buffered saline/dimethylsulfoxide (PBS/DMSO) (vehicles), PBS/ANTU, and KGF/ANTU. At 90 min after ANTU injection the lungs were removed, ventilated, and perfused ex vivo for 180 min. Quantification of fluorescein isothiocyanate (FITC)-labeled dextran in bronchoalveolar lavage fluid (BALF) was used to assess alveolar capillary barrier permeability. KGF attenuated ANTU-induced edema and blockade of sodium transport, with ouabain (10(-3) M) or amiloride (10(-4) M) added ex vivo reversed this effect. FITC-dextran was increased in the PBS/ANTU group as compared with the PBS/DMSO group, indicating permeability edema. In the KGF/ANTU group, there was concentration of BALF FITC-dextran, consistent with permeability edema and increased alveolar fluid export. Albumin space measurements showed similar increases in permeability in the PBS/ANTU and KGF/ANTU groups. Extravascular lung water (measured with radiolabeled erythrocytes) was decreased in the KGF/ANTU group. Following KGF pretreatment, uninjured lungs exported more intratracheal PBS than normal lungs following terbutaline stimulation ex vivo. In conclusion, KGF, through type II alveolar pneumocyte hyperplasia with increased sodium-potassium-adenosine triphosphatase (Na,K-ATPase) activity, attenuated ANTU-induced edema formation by potentiating alveolar fluid clearance.
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PMID:Keratinocyte growth factor increases transalveolar sodium reabsorption in normal and injured rat lungs. 915 91


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