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)

The effect of high concentrations of glucose on Na, K-ATPase activity and the polyol pathway was studied using cultured bovine aortic endothelial cells. Na, K-ATPase activity was expressed as ouabain-sensitive K+ uptake. A significant decrease in Na, K-ATPase activity with an intracellular accumulation of sorbitol was found in confluent endothelial cells incubated with 400 mg/dl glucose for 96 h. However, there was no significant change in the Na, K-ATPase activity or sorbitol content of the cells incubated with 100 mg/dl glucose plus 300 mg/dl mannitol. The decrease in Na, K-ATPase induced by the high glucose concentration was restored by the simultaneous addition of 10(-4) M ponalrestat (ICI 128,436; Statil), an aldose reductase inhibitor. The addition of this agent also significantly reduced the increase in sorbitol induced by high glucose levels. These results suggest that the decrease in Na, K-ATPase activity induced in cultured aortic endothelial cells by high concentrations of glucose may be caused in part by the accumulation of sorbitol.
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PMID:Effect of glucose on Na, K-ATPase activity in cultured bovine aortic endothelial cells. 131 29

1. The effects of a six week period of streptozotocin-induced diabetes on tissue catecholamines and on in vivo noradrenaline turnover were assessed in rats. 2. Noradrenaline concentrations measured in heart ventricle, terminal ileum, vas deferens, spleen and adrenal tissue from the diabetic rats were all found to be elevated compared to those found in control rat tissues. The adrenaline contents of the adrenal glands were also raised in these animals. 3. Noradrenaline turnover in heart ventricle, terminal ileum and vas deferens was estimated from the decline in tissue content of the amine following inhibition of its synthesis with alpha-methyl-p-tyrosine. Turnover was found to be increased in all three tissues. 4. The involvement of the polyol pathway in the above changes was investigated by examining the effects of continuous treatment with an aldose reductase inhibitor, Statil (ICI 128436) or dietary myo-inositol supplementation. Either treatment was found to prevent or reduce the increases in tissue noradrenaline and in its turnover. Myo-inositol treatment also partially prevented the rise in adrenal adrenaline. 5. It is concluded that the elevation of tissue catecholamines and of noradrenaline turnover by diabetes was related to myo-inositol depletion secondary to excessive sorbitol synthesis. Possible mechanisms for the observed increase in noradrenaline turnover could involve Na+, K+-ATPase depression.
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PMID:Tissue noradrenaline and the polyol pathway in experimentally diabetic rats. 250 23

Opioid agonists of the mu, kappa and delta types stimulated low-Km guanosine triphosphatase (GTPase) in membranes, from the brain of the rat by up to 34%, with potencies the rank order of which corresponded to the respective binding affinities to opioid receptor. In general, kappa ligands stimulated GTPase to a lesser degree than mu or delta opiates. The coupling of a given type of opioid receptor to GTPase was resolved by direct or protective alkylation of the other receptors. Treatment of the membranes with beta-funaltrexamine abolished the stimulation of GTPase by sufentanil and levorphanol (mu), but not by bremazocine (kappa) or DSLET (delta). On the other hand, prior incubation with Superfit, an alkylating agent with selectivity for the delta opioid receptor, specifically eliminated the effect of DSLET. Partial alkylation by increasing concentrations of Superfit gradually reduced the extent of stimulation of GTPase by DSLET. The successive treatment of membranes with Superfit and beta-funaltrexamine blocked the actions of DSLET, sufentanil and levorphanol, but had no effect on the stimulation of the GTPase by bremazocine. Selective coupling of an opioid receptor to GTPase was also obtained after incubation of membranes with beta-chlornaltrexamine in the presence of protective concentrations of mu, kappa or delta opioid ligands. Alkylation resolved the coupling of the non-selective opiate etorphine: the sum of stimulation of GTPase in the receptor-selective membranes equalled maximal stimulation of enzyme in untreated membranes. Naloxone blocked the stimulation of GTPase by mu, kappa or delta agonists, but ICI-174,864 specifically inhibited the effect of DSLET.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coupling of multiple opioid receptors to GTPase following selective receptor alkylation in brain membranes. 283 May 55

Increased circulating adrenaline produces systemic hypokalaemia by the stimulation of a membrane bound Na/K ATPase. In man, this enzyme appears to be linked to an adrenoceptor of the beta-subtype. We have further studied the subtype of beta-adrenoceptor involved by infusing adrenaline intravenously in normal volunteers after pretreatment with either a selective beta 2 antagonist (ICI 118551) or placebo. During the adrenaline infusion the serum potassium fell from 4.08 +/- 0.21 to 3.32 +/- 0.25 mmol/l (P less than 0.002). This adrenaline induced hypokalaemia was completely blocked by ICI 118551 (3.82 +/- 0.13 to 4.03 +/- 0.22 mmol/l, NS). Adrenaline also caused electrocardiographic changes of T wave flattening (-1.8 +/- 1.5 mm, P less than 0.05) whereas the T wave height increased after ICI 118551 (+ 1.0 +/- 0.9 mm, P less than 0.05). This suggests that adrenaline acts via beta 2 adrenoceptors in man to cause potassium influx and systemic hypokalaemia.
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PMID:Adrenaline causes hypokalaemia in man by beta 2 adrenoceptor stimulation. 614 31

Vascular endothelial cells, which are polyfunctional, play an important role in the pathogenesis of diabetic complications. The increase in vascular permeability, ie, regulated by vascular endothelial cells, has been reported in patients with diabetes mellitus complicated by angiopathy. To determine the role of hyperglycemia in endothelial cell permeability, we examined the effect of high concentrations of glucose on the permeability of cultured bovine aortic endothelial cells. The permeations of albumin and fluorescein-labeled dextran (FD) across endothelial cell monolayers were increased when cultured with a high concentration of glucose (400 mg/dL). This increased permeation of albumin but not FD was temperature-dependent and was partially reduced by adding 100 mumol/L ponalrestat (ICI 128,436, Statil; ICI, Cheshire, UK), which is an aldose reductase inhibitor. Stimulation or inhibition of Na,K-adenosine triphosphatase (ATPase) in bovine aortic endothelial cells failed to alter their permeability. These findings suggest that high concentrations of glucose enhance transendothelial permeability of albumin in part by activating the polyol pathway, but independently of Na,K-ATPase activity.
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PMID:Increased transendothelial permeation of albumin by high glucose concentration. 754 Feb 48

In anesthetized rats, injection of the beta 2-adrenoceptor (beta 2-AR) agonist clenbuterol (0.45 mumol/kg) caused a marked stimulation of 86RbCl (Rb) uptake by skeletal muscle, but had no effect on other tissues; soleus muscle showed the largest (144% increase) response. Injection of another beta 2-AR agonist (salbutamol 0.45 mumol/kg) had no effect on Rb uptake by any tissue except soleus muscle (83%). Both agonists increased body (colonic) temperature to the same extent. A 3-day treatment with salbutamol as a dietary admixture had no effect on body weight, muscle mass, or tissue Rb uptake, whereas the same treatment using clenbuterol produced significant increases in body weight and muscle mass and significant decreases in Rb uptake in three of the four muscle groups studied; Rb uptake in soleus was not affected. In another experiment, the short-term effect of clenbuterol injection on muscle Rb uptake was found to be resistant to a high dose (20 mg/kg) of the selective beta 2-AR antagonist ICI 118551. It was concluded that the selective effects of short-term administration of clenbuterol on muscle Rb uptake, coupled with its effects over 3 days on Rb uptake and muscle hypertrophy, implicate beta-AR modulation of cation transport (possibly via Na,K-adenosine triphosphatase [ATPase] activity) in the anabolic effects of clenbuterol on muscle protein deposition. Since the stimulation of Rb uptake by clenbuterol was resistant to high doses of a selective beta 2-AR antagonist and since salbutamol had little or no effect on muscle hypertrophy or Rb uptake, it is suggested that clenbuterol may exert its effects via an atypical beta-AR.
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PMID:Effects of clenbuterol and salbutamol on tissue rubidium uptake in vivo. 785 56

We recently reported a novel intracellular mechanism of renal Na-K-ATPase regulation by agents that increase cell cAMP, which involves protein kinase A-phospholipase A2 and is mediated by one or more arachidonic acid metabolites (Satoh, T., H. T. Cohen, and A. I. Katz. 1992. J. Clin. Invest. 89:1496). The present studies were, therefore, designed to assess the role of eicosanoids in the modulation of Na-K-ATPase activity in the rat cortical collecting duct. The effect of various cAMP agonists (dopamine, fenoldopam, vasopressin, forskolin, and dibutyryl cAMP), which inhibited the pump to a similar extent (approximately 50%), was independent of altered Na entry as it was elicited in the presence of amiloride or nystatin, or when NaCl was replaced with choline Cl. This effect was completely blocked by SKF 525A or ethoxyresorufin, two inhibitors of the cytochrome P450-dependent monooxygenase pathway, or by pretreating the animals with CoCl2, which depletes cytochrome P450. Equimolar concentrations (10(-7) M) of the cyclooxygenase inhibitors indomethacin or meclofenamate caused only a partial inhibition of the cAMP agonists' effect on the pump, whereas nordihydroguaiaretic acid or A 63162, two inhibitors of the lipoxygenase pathway, were without effect. Furthermore, two products of this pathway, leukotriene B4 and leukotriene D4, had no effect on Na-K-ATPase activity, and ICI 198615, a leukotriene receptor antagonist, did not alter pump inhibition by cAMP agonists. Several P450 monoxygenase arachidonic acid metabolites (5,6-epoxyeicosatrienoic acid; 11,12-epoxyeicosatrienoic acid; 11,12-dihydroxyeicosatrienoic acid; and 12(R)-hydroxyeicosatetraenoic acid) as well as PGE2 inhibited the Na:K pump in dose-dependent manner, but the effect of PGE2 was blocked when Na availability was altered, whereas that of 12(R)-HETE remained unchanged. We conclude that the cytochrome P450-monooxygenase pathway of the arachidonic acid cascade plays a major role in the modulation of Na:K pump activity by eicosanoids in the rat cortical collecting duct, and that products of the cyclooxygenase pathway may contribute to pump inhibition indirectly, by decreasing intracellular Na.
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PMID:Intracellular signaling in the regulation of renal Na-K-ATPase. II. Role of eicosanoids. 838 20

We conducted studies to determine whether functional beta 2-adrenoceptors are present in cultured rat proximal tubule epithelial cells. To determine whether cultured cells maintain polarity with respect to sodium transport, cells were acid loaded. Acid loading resulted in stimulation of sodium transport. Exposure of acid-loaded cells to alkaline extracellular pH further enhanced sodium transport (22Na flux at pH 7.50 was 68.1 +/- 44% above pH 7.00, P < 0.05). Cultured proximal tubules also exhibited basolateral 86Rb uptake, 65% of which was ouabain sensitive. Thus cultured cells maintain apical Na/H antiport and basolateral Na-K-adenosinetriphosphatase (Na-K-ATPase). Metaproterenol (10(-6) M), a selective beta 2-agonist, stimulated Na-K-ATPase activity by 36 +/- 6% above control (P < 0.05). The stimulatory effect was blocked by ICI-118551, a selective beta 2-antagonist. To determine whether metaproterenol-dependent increases in Na-K-ATPase were dependent on apical sodium entry, apical entry was blocked with dimethylamiloride or maximized with monensin. Both dimethylamiloride and monensin prevented metaproterenol activation of Na-K-ATPase. Metaproterenol-mediated increases in Na-K-ATPase activity were associated with increases in sodium transport (27 +/- 10% above control, P < 0.05), which was prevented by dimethylamiloride. In contrast to isoproterenol, metaproterenol did not stimulate cAMP production. In summary, we have shown that functional beta 2-adrenoceptors are present on cultured rat proximal tubules. beta 2-Adrenoceptor activation results in increases in Na-K-ATPase and Na transport as a consequence of increased apical sodium entry.
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PMID:Beta 2-adrenergic function in cultured rat proximal tubule epithelial cells. 876 Feb 45

Estrogen and progesterone, while regulating uterine functions, also regulate the number of caveolae and the level of caveolin. Large numbers of caveolae, as well as elevated expression of caveolin-1 and caveolin-2 isoforms in the myometrium of ovariectomised (OVX) rats were detected. 17beta-estradiol (E2) has a downregulating effect: the treatment of OVX rats with E2 (5 microg/animal) reduced the formation of caveolae by approx. 90%. Western blots clearly demonstrated the reduction of membrane caveolin-1 and -2 content. Progesterone treatment (2.5 mg/animal) alone did not cause any substantial change, but prevented the effect of estrogen. Control experiments showed that the quantity of Na+/K+-ATPase, a plasma membrane protein excluded from caveolae, was not downregulated by E2. The administration of the pure estrogen receptor (ERalpha) antagonist ICI 182,780 (1 mg/animal) not only compensated for the inhibitory effect of E2, but further increased the level of caveolin-1 in the myometrium of OVX rats and facilitated the formation of caveolae by approximately 70%. In contrast, the partial antagonist tamoxifen (1 mg/animal) mimicked the effect of estrogen. The amount of caveolin also changed during pregnancy. During the first half of pregnancy the expression of caveolin was suppressed, but it gradually increased until delivery. Our results indicate that the formation and number of caveolae are influenced by the physiological state of the uterus in a hormone dependent manner.
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PMID:Estrogen downregulates the number of caveolae and the level of caveolin in uterine smooth muscle. 1148 2

Estrogenic compounds have been shown to protect neurons from a variety of toxic stimuli in vitro and in vivo and depletion of estrogen at menopause has been associated with increased risk of neurodegenerative diseases. Genistein is an isoflavone soy derivative that binds to estrogen receptors with selective estrogen receptor modulator (SERM) properties. Recent FDA recommendations of soy intake for cholesterol reduction have prompted investigation into the potentially estrogenic role of dietary soy phytochemicals in the brain. In this study, we have shown that 50nM genistein significantly reduces neuronal apoptosis in an estrogen receptor-dependent manner. The importance of apoptosis in the brain has been recognized with regard to organization of the developing brain as well as degeneration in response to disease or stroke; however, the effects of estrogenic compounds on neuronal apoptosis have not been thoroughly examined. We developed a model of apoptotic toxicity in primary cortical neurons by using the endoplasmic reticulum (ER) calcium-ATPase inhibitor, thapsigargin, to test potential anti-apoptotic effects of 17beta-estradiol and genistein. Estrogen receptor beta, but not estrogen receptor alpha, was detected in our primary neuron cultures. Thapsigargin-induced apoptosis was confirmed by loss of mitochondrial function, DNA laddering, nuclear condensation and fragmentation, and caspase activation. Both 17beta-estradiol and genistein reduced the number of apoptotic neurons and reduced the number of neurons containing active caspase-3. This effect was blocked by co-addition of ICI 182780. Our results demonstrate that genistein and 17beta-estradiol have comparable anti-apoptotic properties in primary cortical neurons and that these properties are mediated through estrogen receptors.
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PMID:17beta-Estradiol and the phytoestrogen genistein attenuate neuronal apoptosis induced by the endoplasmic reticulum calcium-ATPase inhibitor thapsigargin. 1244 Nov 88


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