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)

Several forms of cardiac adaptation to stress are known, differing in the evoking stress, in the time needed for adaptation and in the duration of the protective effect. A delayed adaptation produced a late appearing, prolonged protection against consequences of ischemia, such as early morphological changes, early and late postocclusion and reperfusion arrhythmias due to coronary artery occlusion or ouabain intoxication. Delayed adaptation was evoked by ischemic stress (repeated brief periods of rapid cardiac pacing or brief coronary occlusions) or by drugs (prostaglandin I2 and its stable derivatives). The protection produced by delayed adaptation proved to be time- and dose-dependent. Optimal effects appeared 24 to 48 h after treatment with an optimal dose of 50 microg/kg 7-oxo-prostacyclin or 10 microg/kg Iloprost. It is suggested that the mechanism of delayed cardioprotection is based on the fact that the stress-evoking adaptation stimulates the adenylate-cyclase/cyclic adenosine monophosphate (cAMP) system; the resulting elevation of cardiac cAMP level triggers the induction of some key enzymes such as Na/K-ATPase and phosphodiesterase (PDE) isoforms I and IV. Increased amount and activity of Na/K-ATPase accounts for preservation of normal membrane function and moderation of ischemic loss of potassium, and accumulation of sodium and calcium in the myocardium, as well as for reduced ouabain toxicity. The detrimental consequences of heavy stress-induced accumulation of cAMP in the heart are mitigated by hydrolysis of the latter, carried out by an enhanced amount and activity of PDE isoforms. Response to beta-adrenergic stimuli is also attenuated. In addition, electrophysiological changes such as prolongation of the effective refractory period and of the action potential duration may attenuate arrhythmias due to ischemia and reperfusion.
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PMID:On the mechanism and possible therapeutic application of delayed cardiac adaptation to stress. 860 40

1 The blocker of endoplasmic reticulum Ca(2+)-ATPase, 2,5-di-(tert-butyl)-1,4-benzohydroquinone (BHQ) was shown to inhibit formation of prostaglandin E2 and prostacyclin in the osteoblast-like cell lines, MC3T3-E1 and ROS 17/2.8, respectively, in a dose-dependent manner with an IC50 of 0.5-1 microM. Inhibition was observed with various stimuli (arachidonic acid, bradykinin, melittin and calcium ionophore, A23187). 2 This effect was also observed in human platelets, where BHQ dose-dependently blocked thromboxane biosynthesis and formation of 12-hydroxy-heptadecatrienoic acid after stimulation with arachidonic acid, but not formation of 12-hydroxy-eicosatetraenoic acid. 3 Inhibition of prostaglandin E2 formation in MC3T3-E1 cells was not observed with thapsigargin after stimulation with arachidonic acid, A23187 or melittin, whereas bradykinin-induced prostaglandin E2 biosynthesis was blocked. 4 Taken together, the results suggest a direct inhibitory action of BHQ on the cyclo-oxygenase in these three cell systems.
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PMID:Inhibition of prostanoid formation in intact cells by 2,5-di-(tert-butyl)-1,4-benzohydroquinone, a blocker of Ca(2+)-ATPases. 882 46

The damage to the liver appears to be an important aspect of multisystem organ failure in acute pancreatitis with poor prognosis. The objective of this study was to evaluate the protective effect of stable prostacyclin analogue--tilsuprost on the liver energy metabolism in taurocholate pancreatitis in rats preceded by acute ethanol intake. The respiratory control ratio (RCR) and ADP/O ratio of liver mitochondria with glutamate+malate as substrates and mitochondrial DNP (uncoupler)-dependent ATPase activity were significantly depressed after 12 h of taurocholate pancreatitis-the effects that were not significantly aggravated by antecedent acute ethanol intake. Tilsuprost (0.3 mg/kg i.g.) given just before induction of pancreatitis partly prevented the impairment of mitochondrial oxidative and phosphorylative functions, however these positive effects were limited in acute pancreatitis preceded by acute ethanol intake. These results suggest that prostacyclin analogues could be effective in the treatment of hepatic complications in acute pancreatitis, however their effectiveness could be limited in the case of acute ethanol antecedent abuse.
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PMID:The effect of tilsuprost on the liver mitochondria in taurocholate pancreatitis in rats with antecedent acute ethanol abuse. 887 59

It is demonstrated a fast and significant depression in the sarcolemmal (Na,K)-ATPase activity that occurs as early as 25 sec after the onset of Ca2+ depletion, and participates in the development of Ca(2+)-paradox in the rat heart. Pretreatment of the animals with 7-oxo-prostacyclin (PGI2) 24-48 h prior to the experiment prevented fairly the Ca(2+)-depletion-induced depression in (Na,K)ATPase activity and the accompanying structural and functional damage to the heart and sarcolemma during Ca(2+)-depletion as well as the development of Ca(2+)-paradox during the subsequent Ca(2+)-repletion. Pretreatment with PGI2 was chosen intentionally because previous experiments revealed, that in its late effect the drug is acting via stabilizing the membranes due induction of high activity of (Na,K)-ATPase that has increased affinity to ATP. From results obtained the following may be concluded: If during the phase of Ca(2+)-deprivation, the capability of heart sarcolemma to maintain sodium extrusion remains preserved, the expected aggravation of Ca(2+)-overload injury to Ca(2+)-paradox that would develop during Ca(2+)-repletion, may be definitely prevented. Sufficiently preserved (Na,K)-ATPase activity, hand in hand with stabilized sarcolemmal structure, may prevent an accumulation of sodium beneath the sarcolemma and consequently also an overexcessive entry of Ca2+ into the myocytes.
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PMID:Prevention by 7-oxo-prostacyclin of the calcium paradox in rat heart: role of the sarcolemmal (Na,K)-ATPase. 890 81

We previously demonstrated that the antiprogestogen RU 486, when superfused on myometrial strips, induces a rapid decrease in spontaneous uterine contractile frequency, an increase in amplitude and duration of contractions, and a concomitant decrease in 6-keto PGF(1alpha) release. In this study, we present further work on the role of calcium transients and the involvement of the PLC/PKC pathway in mediating RU 486 effects. We found no clear causal relationship between the spontaneous contractility controlled by external Ca++ concentration and 6-keto PGF(1alpha) release depending mostly on intracellular Ca++ mobilization. We show that RU 486 strengthened the inhibitory effect of TMB8, a potent inhibitor of internal calcium, on both spontaneous contractility and 6-keto PGF(1alpha), release and antagonized the stimulatory action of thapsigargin, a toxin blocking the endoplasmic reticulum calcium pump (ER Ca++ ATPase). These data indicate that RU 486 could act as an inhibitor of intracellular Ca++ mobilization. A slight but significant decrease of the prostanoid liberation was observed in the presence of U73122, an inhibitor of PLC, but not in the presence of neomycin, another PLC inhibitory compound. PKC inhibitors, staurosporine and H7 did not significantly affect spontaneous 6-keto PGF1alpha release, showing that PIP2 hydrolysis and PKC pathway were not involved in the basal release of the prostacyclin metabolite. Vasopressin (AVP), an agent known to induce contractility of the non-pregnant human uterus, markedly increased 6-keto PGF(1alpha) release in a dose-dependent manner. Stimulation of GTP-regulated proteins (G proteins) by ALF4 was accompanied by a rise in 6-keto PGF(1alpha) liberation and a high contractile activity. The effects of both vasopressin and ALF4- were not significantly opposed by RU 486, indicating that other sources of Ca++, not controlled by the steroid, were involved in the agonist-stimulated prostanoid release. Studies with structurally related RU 486 analogues showed that the steroid effects were not dependent on their antihormonal activity, but rather on a specific 11beta arylsubstitution and a 17beta-hydroxy-13beta-methyl configuration of the 4,9-estradien-3-one molecule.
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PMID:RU 38486 inhibits intracellular calcium mobilization and PGI2 release from human myometrium: mechanisms of action. 900 39

The popularity of polyunsaturated oils used in food applications and preparation continues to appreciate as a result of positive health claims. With polyunsaturated oils inherently more susceptible to oxidative and thermal degradation, the formation of new fatty acid species increases considerably. The presence of one species known as cyclic fatty acid monomers (CFAM) has been detected as a component of many oils subjected to various thermal processes including deep-fat frying. The effect of CFAM on metabolic processes has not been fully characterized. In this study, confluent porcine aortic endothelial cells incorporated CFAM into their polar and nonpolar lipid fractions following a 48-h exposure to 31 and 62 ppm CFAM in the culture medium. Subsequently, the influence of CFAM incorporation on various membrane-dependent physical properties and biochemical processes was investigated. CFAM decreased the lipid packing order of the membrane bilayer core but did not alter the lipid packing order of lipid chain segments at or near the lipid-water interface of the membrane. CFAM led to significant reductions in Ca2+ ATPase activity and monolayer integrity while eliciting a significant increase of prostacyclin synthesis and secretion.
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PMID:The effects of cyclic fatty acid monomers on cultured porcine endothelial cells. 930 32

The effects of exogenous platelet activating factor (PAF), BN52021 (an antagonist of PAF receptor), indomethacin and verapamil on the production of TxA2, PGI2 and activity of Ca(2+)-ATPase were investigated in rabbit intra-pulmonary smooth muscle cells (PASMCs). The results were as follows: (1) Under basic condition, active AA metablism was present in PASMCs. (2) Significant increase of TxA2 and PGI2 but not their ratio may result from binding of PAF receptor and activation of cyclooxgenase. (3) Activity of Ca(2+)-ATPase could be inhibited by exogenous PAF. (4) The inhibitory effect of PAF on PASMCs Ca(2+)-ATPase could be reversed by verapamil.
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PMID:[Effect of platelet activating factor on TxA2, PGI2 and Ca(2+)-ATPase activity in the intra-pulmonary artery smooth muscle cells]. 938 96

In arteries, muscarinic agonists such as acetylcholine release an unidentified, endothelium-derived hyperpolarizing factor (EDHF) which is neither prostacyclin nor nitric oxide. Here we show that EDHF-induced hyperpolarization of smooth muscle and relaxation of small resistance arteries are inhibited by ouabain plus Ba2+; ouabain is a blocker of Na+/K+ ATPase and Ba2+ blocks inwardly rectifying K+ channels. Small increases in the amount of extracellular K+ mimic these effects of EDHF in a ouabain- and Ba2+-sensitive, but endothelium-independent, manner. Acetylcholine hyperpolarizes endothelial cells and increases the K+ concentration in the myoendothelial space; these effects are abolished by charbdotoxin plus apamin. Hyperpolarization of smooth muscle by EDHF is also abolished by this toxin combination, but these toxins do not affect the hyperpolarizaiton of smooth muscle by added K+. These data show that EDHF is K+ that effluxes through charybdotoxin- and apamin-sensitive K+ channels on endothelial cells. The resulting increase in myoendothelial K+ concentration hyperpolarizes and relaxes adjacent smooth-muscle cells by activating Ba2+-sensitive K+ channels and Na+/K+ ATPase. These results show that fluctuations in K+ levels originating within the blood vessel itself are important in regulating mammalian blood pressure and flow.
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PMID:K+ is an endothelium-derived hyperpolarizing factor in rat arteries. 983 27

The protean properties of 20-hydroxyeicosatetraenoic acid (HETE), vasoactivity, mitogenicity, and modulation of transport in key nephron segments, serve as the basis for the essential roles of 20-HETE in the regulation of the renal circulation and electrolyte excretion and as a second messenger for endothelin-1 and mediator of selective renal effects of ANG II. Renal autoregulation and tubular glomerular feedback are mediated by 20-HETE through constriction of preglomerular arterioles, responses that are maintained by 20-HETE inhibition of calcium-activated potassium channels. 20-HETE modulates ion transport in the proximal tubules and the thick ascending limb by affecting the activities of Na+-K+-ATPase and the Na+-K+-2Cl- cotransporter, respectively. The range and diversity of activity of 20-HETE derives in large measure from COX-dependent transformation of 20-HETE to products affecting vasomotion and salt and water excretion. Nitric oxide (NO) exerts a negative modulatory effect on 20-HETE formation; inhibition of NO synthesis produces marked perturbation of renal function resulting from increased 20-HETE production. 20-HETE is an essential component of interactions involving several hormonal systems that have central roles in blood pressure homeostasis, including angiotensins, endothelins, NO, and cytokines. 20-HETE is the preeminent renal eicosanoid, overshadowing PGE2 and PGI2. This review is intended to provide evidence for the physiological roles for cytochrome P-450-derived eicosanoids, particularly 20-HETE, and seeks to extend this knowledge to a conceptual framework for overall cardiovascular function.
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PMID:20-HETE and the kidney: resolution of old problems and new beginnings. 1048 76

In a previous study of cultured preglomerular vascular smooth muscle cells, it was demonstrated that, although the stable prostacyclin analog iloprost alone had no effect on the intracellular calcium concentration ([Ca2+](i)), it did significantly attenuate the increase in [Ca2+](i) stimulated by angiotensin II (AngII). In this study, the mechanisms by which iloprost interacts with calcium signaling pathways stimulated by AngII were examined. [Ca2+](i) was assessed using the calcium-sensitive fluorescent dye fura-2. Initial studies identified two major components of the [Ca2+](i) response to AngII in this homogeneous preparation of vascular smooth muscle cells from renal resistance vessels. Mobilization of internal stores was evident as an immediate TMB-8-sensitive peak increase in [Ca2+](i) (52 +/- 6 to 297 +/- 26 nM, P: < 0.001) in a calcium-free medium. After [Ca2+](i) had returned to baseline levels during continued AngII stimulation, a nifedipine-sensitive entry pathway was revealed by the sustained stimulatory effect of added external calcium, which increased [Ca2+](i) to 112 +/- 13 nM (P: < 0.001). Coadministration of iloprost with AngII attenuated both the immediate peak (154 +/- 14 nM) and sustained plateau (61 +/- 9 nM) phases. Increases in endogenous levels of cAMP induced by the phosphodiesterase inhibitor milrinone mirrored the actions of iloprost, suggesting that the prostacyclin analog exerted its actions via cAMP activation. Blockade of cAMP-dependent protein kinase with KT 5720 reversed the effects of both iloprost and milrinone. When iloprost or milrinone was introduced after the initial mobilization peak had dissipated, the plateau phase of calcium entry was unchanged (92 +/- 9 nM). The concept that iloprost does not directly modulate calcium entry was further supported by data showing that the activation of L-type calcium channels by BAY-K 8644 was unchanged during iloprost treatment. On the basis of the observation that iloprost did not alter thapsigargin stimulation of Ca(2+)-ATPase activity, it is concluded that the actions of cAMP are distinct from increasing calcium uptake into the sarcoplasmic reticulum. This study provides new information on the ability of iloprost to primarily attenuate inositol-1,4,5-triphosphate-mediated calcium mobilization via cAMP, with secondary inhibition of L-type calcium entry channels. These data clarify the mechanism by which prostaglandins buffer AngII constriction in resistance arterioles.
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PMID:Iloprost inhibits inositol-1,4,5-trisphosphate-mediated calcium mobilization stimulated by angiotensin II in cultured preglomerular vascular smooth muscle cells. 1113 46


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