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:3.1.3.5 (5'-nucleotidase)
3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purified plasma membrane fractions of cultured well-differentiated Reuber H35 hepatoma cells were studied after growth in the presence or absence of ethanol. Growth of cells in the presence of ethanol significantly increased plasma membrane 5'-nucleotidase activity but did not influence sodium-potassium adenosinetriphosphatase activity. Fluorescence polarization of lipophilic probes was used to study membrane lipid structure. Steady-state polarization of diphenylhexatriene (DPH), a probe of the hydrophobic core, was significantly lower in plasma membranes from cells grown in 80 mM ethanol for 3 weeks, compared to controls. Decreased polarization of DPH in plasma membranes was observed after 3-weeks growth of cells in as little as 1 mM ethanol. A 1-h exposure to 80 mM ethanol had no effect. Altered DPH polarization was due to a decrease in the order parameter of the probe. The rotational correlation time of the probe was virtually unchanged. Chronic ethanol treatment of cells did not alter the polarization of the membrane surface probe trimethylammoniodiphenylhexatriene. Plasma membranes from cells grown in 80 mM ethanol had decreased contents of both phospholipid and unesterified cholesterol, but the cholesterol to phospholipid ratio was unchanged. The percentages of sphingomyelin and phosphatidylserine in plasma membrane phospholipids were significantly decreased after ethanol treatment, while the phosphatidylcholine/sphingomyelin ratio was increased by 42%. Vesicles prepared from total plasma membrane lipids of ethanol-treated cells, as well as vesicles prepared from polar lipids alone, showed the same alterations in DPH polarization as did plasma membranes. The importance of ethanol metabolism in the observed plasma membrane changes was demonstrated in two ways.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic ethanol increases liver plasma membrane fluidity. 402 34

The relationship between net tubular reabsorption of sodium and renal microsomal sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) was evaluated in hypothyroid and hyperthyroid rats and in age-matched euthyroid controls. Tubular sodium reabsorption per gram of kidney was lower in thyroidectomized rats than in controls (186+/-14 vs. 246+/-12 mueq/min; P < 0.005) and was accompanied by a quantitatively similar reduction in Na-K-ATPase specific activity (49.4+/-2.4 vs. 65.8+/-2.3 mumol inorganic phosphate (P(t))/mg protein per h; P < 0.001). This decrement was present in both cortex and outer medulla, and was limited to Na-K-ATPase since other representative enzymes not involved in sodium transport (magnesium-dependent adenosine triphosphatase [Mg-ATPase], glucose-6-phosphatase, 5'-nucleotidase) remained unchanged or increased in the hypothyroid animals. Conversely, Na-K-ATPase rose when sodium reabsorption increased in euthyroid rats treated with triiodothyronine. Subsequent experiments were performed to determine to what extent the decrease in Na-K-ATPase is due to lack of thyroid hormone per se or to an adaptive response to decreased reabsorptive sodium load. Triiodothyronine in concentrations of 10(-12) to 10(-5) M had no effect in vitro on microsomal Na-K-ATPase of either thyroidectomized or euthyroid rats. When hypothyroid rats were uninephrectomized or treated with methylprednisolone, sodium reabsorption per gram kidney increased markedly and was similar to that of intact controls. Despite persistence of the hypothyroid state, Na-K-ATPase specific activity also increased to levels not significantly different from euthyroid animals. These data suggest that decreased tubular sodium transport is a major determinant of the reduction in renal Na-K-ATPase in thyroid deficiency since the latter can be reversed by increasing sodium reabsorption during continuing hypothyroidism. Furthermore, the modest sodium leak of hypothyroid animals does not appear to be due to decreased Na-K-ATPase since it was not corrected by uninephrectomy despite restoration of both cortical and medullary Na-K-ATPase activity to normal by this maneuver. The close correlation between net sodium reabsorption and Na-K-ATPase in all the experimental situations described here demonstrates that renal Na-K-ATPase changes adaptively in hyper- or hypothyroidism as it does in numerous situations in the normal animal, in accord with its postulated role in the active transport of sodium across the renal tubule.
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PMID:Renal sodium- and potassium-activated adenosine triphosphatase and sodium reabsorption in the hypothyroid rat. 434 43

Quantitative measurements of (Na+,K+)-ATPase activity and numbers of (Na+,K+)-ATPase sites in membranes from quiescent and regenerating rat liver have been made using an anticatalytic monoclonal antibody (9-A5) that binds to alpha subunits of the sodium pump (Schenk, D. B., and Leffert, H. L. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 5281-5285). To validate the measurements, kinetic properties of 9-A5 binding to plasma membrane sodium pumps, specificity and requirements of the reactions, and mechanisms by which 9-A5 inhibits (Na+,K+)-ATPase were analyzed. 125I-9-A5 binding is saturable and reversible (k1 = 1.8 X 10(6) X M-1 X S-1; k2 = 2.7 X 10(-4) X S-1). At equilibrium, 9-A5 binds to a single class of sites revealed by Scatchard plots (KD[app] = 0.64 nM, Bmax = 29.3 pmol/mg of proteins; = 238,000 sites X cell-1). This binding requires monovalent cations (sodium, potassium, or lithium); is blocked by purified (Na+,K+)-ATPase; is inhibited noncompetitively by ATP (KI[app] = 0.5 mM); and is unaffected by ouabain. 9-A5 inhibits ATP-stimulated (Na+,K+)-ATPase noncompetitively by blocking sodium-dependent phosphorylation of alpha subunits of liver or kidney membrane (Na+,K+)-ATPase. Twelve h after 67% hepatectomy, maximal 125I-9-A5 binding to plasma membranes from regenerating liver falls 30 +/- 7% compared to sham-operated controls (p less than 0.01). In contrast, (Na+,K+)-ATPase activity in regenerating liver membranes rises 58 +/- 12% compared to controls (p less than 0.03). Similar experiments with particulate fractions from regenerating liver show insignificant decreases in maximal 125I-9-A5 binding (22 +/- 12%) but large increases in (Na+,K+)-ATPase activity (325 +/- 14%) compared to controls (p less than 0.001). No differences among groups are seen in KD values for 9-A5 binding or in the activities of plasma membrane 5'-nucleotidase (EC 3.1.3.5). Thus, stimulation of the sodium pump during the late prereplicative phase of liver regeneration is not accompanied by increases in the numbers of (Na+,K+)-ATPase sites. Instead, it appears that preexisting (Na+,K+)-ATPases are activated specifically before DNA replication starts.
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PMID:Use of a monoclonal antibody to quantify (Na+,K+)-ATPase activity and sites in normal and regenerating rat liver. 609 83

Although acute alterations in Ca2+ fluxes may mediate the skeletal responses to certain humoral agents, the processes subserving those fluxes are not well understood. We have sought evidence for Ca2+-dependent ATPase activity in isolated osteoblast-like cells maintained in primary culture. Two Ca2+-dependent ATPase components were found in a plasma membrane fraction: a high affinity component (half-saturation constant for Ca2+ of 280 nM, Vmax of 13.5 nmol/mg per min) and a low affinity component, which was in reality a divalent cation ATPase, since Mg2+ could replace Ca2+ without loss of activity. The high affinity component exhibited a pH optimum of 7.2 and required Mg2+ for full activity. It was unaffected by potassium or sodium chloride, ouabain or sodium azide, but was inhibited by lanthanum and by the calmodulin antagonist trifluoperazine. This component was prevalent in a subcellular fraction which was also enriched in 5'-nucleotidase and adenylate cyclase activities, suggesting the plasma membrane as its principal location. Osteosarcoma cells, known to resemble osteoblasts in their biological characteristics and responses to bone-seeking hormones, contained similar ATPase activities. Inclusion of purified calmodulin in the assay system caused small non-reproducible increases in the Ca2+-dependent ATPase activity of EGTA-washed membranes. Marked, consistent calmodulin stimulation was demonstrated in membranes exposed previously to trifluoperazine and then washed in trifluoperazine-free buffer. These results indicate the presence of a high affinity, calmodulin-sensitive Ca2+-dependent ATPase in osteoblast-like bone cells. As one determinant of Ca2+ fluxes in bone cells, this enzyme may participate in the hormonal regulation of bone cell function.
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PMID:A high affinity, calmodulin-responsive (Ca2+ + Mg2+)-ATPase in isolated bone cells. 613 20

A preparation of cardiac sarcolemmal membranes is described. These membranes exhibit 9-24-fold purification of (Na+ + K+)-ATPase, potassium-stimulated nitrophenolphosphatase, 5'-nucleotidase, adenylate cyclase, sialic acid content, and beta-receptor number. Sarcolemmal membranes have two classes of binding sites for the calcium entry blocker, bepridil, 70 X 10(12) high-affinity sites/mg, Kd 25-40 nM; and 30 X 10(15) low-affinity sites/mg, Kd 54-70 microM. Binding of bepridil to these sites appears responsible for inhibition of isoprenaline-stimulated and activation of fluoride-stimulated adenylate cyclase. Since basal adenylate cyclase activity is not influenced, bepridil must act not at the catalytic site, but by altering the interactions between beta-receptor and catalytic and regulatory components of adenylate cyclase.
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PMID:Two site binding of bepridil and modulation of adenylate cyclase in cardiac sarcolemmal membranes. 631 30

After the intraperitoneal administration of 0.5 mEq 134 CsCI . kg -1 to mice, the maximum cesium level in the kidney's, heart, lungs and liver was found in the first hour (T 1/2 13 h), in the muscles after 8 h (T 1/2 180 h), in the brain after 24 h (T 1/2 140 h) and in the blood after 24 h. Maximum cesium levels were found in the muscles. Rats excreted about 17% of the administered dose in 24 h and 38% in 144 h. Most of the cesium (about 90%) is excreted in the urine. In rats, equalization of the plasma and RBC cesium levels takes longer than 6h. Cesium transport is not entirely dependent on the ATPase system, as shown by the results given by the crude mitochondrial fraction with a reduced potassium content. Among the various univalent ions studied, the effect of cesium on creatine kinase, 5'-nucleotidase, phosphodiesterase and deaminase activity was the smallest.
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PMID:Distribution of cesium in the organism and its effect on the nucleotide metabolism enzymes. 645 57

At the neuromuscular junction and possibly also at the synaptic level in the brain, the main sequence of events (see Fig. 5) that involves purines in modulation of ACh release includes the following observations: (1) storage of ATP and its release either together with, or independently of acetylcholine. ATP is also released from the post-junctional component. Adenosine as such is released either from the motor nerve terminals or from the post-junctional component. (2) There is extracellular hydrolysis of ATP to adenosine, which is the active substance to modulate transmitter release. The key enzyme in the conversion of AMP into adenosine is the ecto 5'-nucleotidase. When ecto-5'-nucleotidase is not available (e.g. in cholinergic nerve terminals of the cerebral cortex) ATP as such exerts the neuromodulatory role normally fulfilled by adenosine. (3) Both the inhibition and the excitation induced by adenosine on ACh release in the rat is inactivated through up-take and deamination. (4) Adenosine-induced inhibition of ACh release is mediated via A1 receptors and the excitation via A2a receptors. The A2a receptors are positively coupled to the adenylate cyclase/cyclic AMP system, whereas the presynaptic A1 receptors (a) may be negatively linked to adenylate cyclase and (b) to phospholipase C, and, upon stimulation, (c) increase potassium conductance and (d) decrease calcium conductance. (5) Activation of A2a receptors is essential for substances that facilitate ACh release (e.g. CGRP, forskolin) to exert their effects, as well as for induction of nicotinic autofacilitatory receptor desensitization. (6) There are interactions between A1 and A2a receptors. Thus, the net adenosine neuromodulatory response is the resultant, at each moment, of the relative degree of activation of each one of these receptors. This relative activation depends upon the intensity (frequency, pulse duration) of stimulation of the motor nerve terminals. (7) Adenosine released as such seems to preferentially activate A1 receptors, whereas the adenosine formed from metabolism of adenine nucleotides prefers to activate the A2a receptors. In conclusion, to find out precisely what occurs with ACh in transmitting its message at the synaptic level, one has to consider the subtle ways used by purines to modulate the ACh response. It therefore appears of interest that pharmacological and therapeutic strategies use this knowledge to approach cholinergic transmission deficiencies based upon reduction of ACh release.
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PMID:Purinergic regulation of acetylcholine release. 900 12

The aim of the present study was to investigate possible relationships in piglets between myocardial energy-related metabolites and intracellular electrolytes during open-chest cardiopulmonary resuscitation (OCCPR) supplemented by the administration of alkaline buffers with varying sodium content. Our hypothesis was that an increasing myocardial intracellular sodium content would decrease the intracellular energy stores. In addition to haemodynamics, acid-base and blood gas variables were analysed, and myocardial biopsies were collected before and during OCCPR as well as after the return of spontaneous circulation. After a period of 4 min of untreated ventricular fibrillation (VF). 25 piglets were randomly allocated to one of four groups: OCCPR with normal saline (n = 5); OCCPR with sodium bicarbonate (SB) (n = 7); OCCPR with Tris buffer mixture (TBM) (n = 7); and a totally untreated control group (n = 6). The results showed that 4 min of untreated VF almost eradicated creatine phosphate (CrP) and that the ATP/ADP ratio decreased to 1.5-2.0. During OCCPR with normal saline, the myocardial content of CrP increased, whereas lactate, ATP and ADP levelled off and AMP decreased, causing an increased ATP/ADP ratio. The adenosine and inosine contents increased, whereas inosine monophosphate was unchanged at a low level, the adenosine and inosine contents being inversely correlated with the total content of adenine nucleotides. In both buffered groups, the increase in most energy-related metabolites (CrP, ATP, ADP, AMP and the ATP/ADP quotient) was less and in lactate more pronounced than in the group not being buffered, with no difference between the groups receiving SB or TBM. Although the intracellular potassium content was unaltered, the sodium, chloride and calcium concentration increased, more so in the group receiving SB. The intracellular content of sodium was correlated with that of calcium. Thus, buffering increased the myocardial AMP degradation during OCCPR by increasing the flux via the 5'-nucleotidase reaction, and SB increased the intracellular contents of sodium and calcium to a greater extent than did TBM.
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PMID:Response of myocardial cellular energy metabolism to variation of buffer composition during open-chest experimental cardiopulmonary resuscitation in the pig. 917 50

Tumour cell drug resistance is a major problem in cancer chemotherapy. Essential fatty acids have been shown to be cytotoxic to a variety of tumour cells in vitro. But, the effect of these fatty acids on tumour cell drug resistance has not been well characterized. Gamma-linolenic acid (GLA) of the n-6 series and eicosapentaenoic acid (EPA) of the n-3 series potentiated the cytotoxicity of anti-cancer drugs: vincristine, cis-platinum and doxorubicin on human cervical carcinoma (HeLa) cells in vitro. Alpha-linolenic acid (ALA), GLA, EPA and docosahexaenoic acid (DHA) enhanced the uptake of vincristine by HeLa cells. In addition, DHA, EPA, GLA and DGLA were found to be cytotoxic to both vincristine-sensitive (KB-3-1) and -resistant (KB-ChR-8-5) human cervical carcinoma cells in vitro. Pre-incubation of vincristine-resistant cells with sub-optimal doses of fatty acids enhanced the cytotoxic action of vincristine. GLA, DGLA, AA, EPA and DHA enhanced the uptake and inhibited the efflux of vincristine and thus, augmented the intracellular concentration of the anti-cancer drug(s). Fatty acid analysis of KB-3-1 and KB-ChR-8-5 cells showed that the latter contained low amounts of ALA, GLA, 22:5 n-3 and DHA in comparison to the vincristine-sensitive cells. The concentrations of GLA and DHA were increased 10-15 fold in the phospholipid, free fatty acid and ether lipid cellular lipid pools of GLA and DHA treated cells. These results coupled with the observation that various fatty acids can alter the activity of cell membrane bound enzymes such as sodium-potassium-ATPase and 5'-nucleotidase, levels of various anti-oxidants, p53 expression and the concentrations of protein kinase C suggest that essential fatty acids and their metabolites can reverse tumour cell drug-resistance at least in vitro.
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PMID:Can tumour cell drug resistance be reversed by essential fatty acids and their metabolites? 948 65

1. Myocardial tolerance against infarction is substantially increased by exposing myocytes to 3-10 min transient ischaemia. In this phenomenon, termed 'preconditioning', the adenosine receptor is one of the redundant triggers and the best characterized factor in the cardioprotective mechanism. 2. An increase in interstitial adenosine during preconditioning is thought to be derived primarily from hydrolysis of 5'-AMP in the myocyte by cytosolic 5'-nucleotidase, although a contribution of ectosolic 5'-nucleotidase remains controversial. Adenosine production during ischaemia is substantially suppressed in the preconditioned myocardium, probably due to a decrease in ATP utilization. 3. The adenosine receptor needs to be activated not only at the time of preconditioning ischemia, but also during ischaemic insult for the preconditioning to be cardioprotective. However, the extent of cardioprotection afforded by preconditioning is primarily determined by the interstitial adenosine level achieved during preconditioning ischaemia, not by the level during sustained ischaemia. These data suggest that a post-receptor mechanism downstream of the adenosine receptor may be up-regulated after preconditioning. 4. Studies in vitro suggest that the subtypes of adenosine receptor relevant to preconditioning against infarction are A1 and A3, the activation of which appears to provide additive protection. The functional interrelationship between these subtypes in vivo remains unknown. 5. An important step downstream of adenosine receptor activation is protein kinase C (PKC), which facilitates opening of ATP-sensitive potassium (KATP) channels, probably leading to enhancement of myocardial tolerance. However, activation of other protein kinases, such as tyrosine kinase, may also be important in preconditioning, depending on the animal species and preconditioning protocols. The PKC isoform and location of KATP channels (i.e. sarcolemmal vs mitochondrial KATP) that induce anti-infarct tolerance in myocytes remain to be identified.
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PMID:Adenosine and preconditioning revisited. 1006 27


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