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)

Hyperglycemia has been shown to diminish Na(+)-K+ ATPase activity in rabbit aorta. To examine the basis for this effect, aortic rings were incubated for 3 h in Krebs-Henseleit solution containing 5.5 or 44 mM glucose, and Na(+)-K+ ATPase activity was then quantified on the basis of ouabain-sensitive (OS) 86Rb-uptake. Incubation with 44 mM glucose medium caused a 60% decrease in Na(+)-K+ ATPase activity in rings with intact endothelium (from 0.22 +/- 0.01 to 0.091 +/- 0.006 nmol/min per mg dry wt; P less than 0.01). Similar decreases (45%; P less than 0.01) in Na(+)-K+ ATPase activity were seen when rings incubated with 5.5 mM glucose were exposed to NG-monomethyl L-arginine (300 microM), an inhibitor of endothelium-derived nitric oxide (EDNO) synthesis or when the endothelium was removed (43% decrease). The decrease in Na(+)-K+ ATPase activity induced by hyperglycemia was totally reversed upon adding to the medium either L-arginine, a precursor of EDNO biosynthesis or sodium nitroprusside, which bypasses endothelium and directly activates the soluble guanylate cyclase in vascular smooth muscle. A decrease in Na(+)-K+ ATPase activity (42%; P less than 0.05), only seen in the presence of endothelium, was also observed in aortas taken directly from alloxan-induced diabetic rabbits. These studies suggest that the decrease in vascular Na(+)-K+ ATPase activity induced by hyperglycemia is related, at least in part, to a decrease in the basal release of EDNO. They also suggest that alterations in basal EDNO release and possibly Na(+)-K+ ATPase activity contribute to the impairment in vascular relaxation caused by hyperglycemia and diabetes.
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PMID:Endothelium-dependent inhibition of Na(+)-K+ ATPase activity in rabbit aorta by hyperglycemia. Possible role of endothelium-derived nitric oxide. 132 96

Hypertension is known to potentiate the risk of congestive heart failure (CHF) in diabetic individuals. Receptor-effector systems for atrial natriuretic peptide (ANP), which is known to regulate intracellular calcium (Ca2+), were studied in the kidney during hypertensive-diabetic cardiomyopathy in rats. Animals were divided into four groups: control, diabetic (D), hypertensive (H), and diabetic plus hypertensive (D + H). Diabetes was induced by a streptozotocin (65 mg/kg) injection and hypertension was induced by abdominal aortic constriction; studies were done at 1 and 6 weeks. Plasma ANP was increased at 1 week in the D, H, and D + H groups. There was a significant increase in the activity of Ca2+ + magnesium (Mg2+) adenosine triphosphatase (ATPase), which acts as a Ca2+ pump, in the kidney basolateral membrane from D, H, and D + H group at the 1 week study. Ca2+ + Mg2+ ATPase, on the other hand, was significantly decreased in the D + H group only at 6 weeks. This was associated with a decrease in plasma ANP, an increase in the kidney ANP receptor number, and a decrease in guanylate cyclase activity. The response of the Ca2+ pump to ANP was also attenuated. Since ANP is known to mediate its cellular effects in part by increasing Ca2+ + Mg2+ ATPase, the observed changes in the D + H group may contribute to the development of nephropathy and CHF.
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PMID:Congestive heart failure in diabetes with hypertension may be due to uncoupling of the atrial natriuretic peptide receptor-effector system in the kidney basolateral membrane. 164 1

Calmodulin is a protein with calcium-dependent binding sites. Binding of calcium ions induces changes in the conformation and activation of many enzymes such as adenylate cyclase, guanylate cyclase, ATPase. Neuroleptic drugs bind calmodulin. Trifluoperazine has a very high affinity for calmodulin. Tricyclic antidepressants and benzodiazepines also bind calmodulin. Binding of neuroleptics inhibits many biological phenomena such as lymphocyte endocytosis, platelets aggregation. When neuroleptics are administrated chronically, calmodulin could act in regulation of the receptors specially in the drug induced supersensitivity of striatum dopamine receptors. These experiments about the regulation of the receptors mediated by calmodulin have been performed ten years ago and their results were not confirmed later. Moreover, binding of calmodulin is not specific of neuroleptic drugs. The effects of neuroleptics on calmodulin, only observed in vitro or with animals, seem to be mainly related to structural properties of the drugs.
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PMID:Could the interaction of neuroleptics with calmodulin be an "explanation" of the psychotropic effects? 168 72

1. When the web of the anaesthetized Xenopus laevis was perfused with Ringer solution maintained at 20 degrees C, radio frequency (RF) burst-type electromagnetic (EM) field radiation not only dilated arterioles of the web which had been preconstricted with noradrenaline, but also dilated arterioles under non-stimulated conditions. The EM field-induced vasodilatation increased slowly and reached a plateau 60 min after the onset of radiation. After the cessation of radiation, vasodilatation remained for 10-20 min, then slowly subsided. 2. When a 10 MHz, 1 V (peak to peak) generator voltage induced a 7.3 milliGauss, 2.19 V cm-1 EM field, the vasodilatory effect was optimum when bursts were applied 50% of the total time at 10 kHz burst rate. 3. The vasodilatory effect was not secondary to dielectric heat in the web, because the EM field was too weak to have produced enough heat to dilate the arterioles and heat would have been constantly conducted away by the perfusion solution. 4. During perfusion with Ringer solution warmed to 30 degrees C, no vasodilatation was found, but perfusion with Ringer solution warmed to 35 degrees C induced only 11% vasodilatation. Perfusion with Ringer solution warmed to 37 degrees C induced irreversible vasoconstriction. The pattern of vasodilatation induced by warm Ringer solution was different from the vasodilatory effect of weak EM field radiation. 5. The extent of the vasodilatory effect was influenced by Ca2+ concentration of the perfusion medium. Under normal Ca2+ conditions arterioles dilated to 126% of the control diameter, while under Ca(2+)-free conditions arterioles dilated to 131% of the control value and under high-Ca2+ conditions (twice the normal level) arterioles dilated to 111% of the control value. This suggests that the vasodilatory effect may be caused by facilitation of Ca2+ outflow, and the extent of this flow may settle down to the equilibrium level of countercurrent flux between Ca2+ influx and outflow. 6. The vasodilatory effect was not inhibited under perfusion with Na(+)-free Ringer solution, suggesting that Na(+)-Ca2+ exchange system may not be involved in the vasodilatory effect. The vasodilatory effect was inhibited by vanadate, an inhibitor of Ca(2+)-ATPase, and was abolished by Methylene Blue, an inhibitor of guanylate cyclase. The evidence suggests that the mechanism of the vasodilatory effect may depend on an increase in Ca2+ outflow through the plasma membrane of the smooth muscle and/or an increase in Ca2+ influx into the sarcoplasmic reticulum.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Non-thermal vasodilatation by radio frequency burst-type electromagnetic field radiation in the frog. 177 Apr 39

1. In the isolated perfused, noradrenaline (NA)-constricted mesenteric arteries of the rat, acetylcholine (0.003-1 nmol), histamine (0.01-10 nmol) and the calcium ionophore A23187 (0.01-1 nmol), caused endothelium-dependent vasodilatation while the vasodilatation by the K+ channel activator BRL 34915 (0.1-1 nmol) was independent of endothelium. 2. The guanylate cyclase inhibitor, methylene blue at 10 microM did not inhibit the action of any of the vasodilators but at 50 microM reduced the vasodilator effect of acetylcholine (ACh), histamine and A23187. 3. Infusion of ouabain or perfusion with K(+)-free or excess K+ (50 mM) Krebs solution reduced the vasodilator effect of ACh, histamine and A23187, suggesting the action of these agents involves, at least in part, activation of Na+/K(+)-ATPase. The vasodilator effect of BRL 34915 was not affected by ouabain, but abolished during perfusion with Krebs solution containing excess K+ or depleted of K+. 4. Five structurally distinct K+ channel blockers (apamin, crude scorpion venom, procaine, quinidine and tetraethylammonium) attenuated the vasodilator effect of ACh, histamine and A23187. The K+ channel blockers, except apamin and crude scorpion venom, also inhibited the vasodilatation produced by BRL 34915. 5. The vasodilator effect of ACh, histamine or A23187 was not altered in mesenteric vessels of pertussis toxin-treated rats, suggesting that the K+ channels associated with the endothelium-dependent vasodilator effect of these agents are either not coupled to G-proteins or are coupled to G-proteins that are insensitive to pertussis toxin. 6. The calcium channel blockers, diltiazem (0.1 or 1 microM), nifedipine (0.01 or 0.1 microM) or nitrendipine (1 nM) attenuated the vasodilatation produced by ACh, histamine, A23187 and also that by BRL 34915. 7. We conclude that endothelium-dependent vasodilatation induced by ACh, histamine and A23187 is mediated via activation of membrane K+ channels and Na+/K+-ATPase. The K+ channels involved in the vasodilator action of these agents are not coupled to pertussis toxin-sensitive G-proteins and appear to be regulated by Ca2 +.
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PMID:Endothelium-dependent and BRL 34915-induced vasodilatation in rat isolated perfused mesenteric arteries: role of G-proteins, K+ and calcium channels. 216 32

1. Depolarization of excitable cells of the central nervous system results in the formation of the second messengers cyclic AMP, cyclic GMP, inositol phosphates, and diacylglycerides. 2. Depolarization-evoked accumulation of cyclic AMP in brain preparations can be accounted for mainly by the release of adenosine, which subsequently interacts with stimulatory adenosine receptor linked to adenylate cyclase. 3. Depolarization-evoked formation of cyclic GMP in brain preparations is linked to activation of voltage-dependent calcium channels, presumably leading to activation of guanylate cyclase by calcium ions. 4. In brain slices depolarization-evoked stimulation of phosphoinositide breakdown and subsequent formation of inositol phosphates and diacylglycerides are linked to activation of voltage-dependent calcium channels, which are sensitive to dihydropyridines, presumably leading to activation of phospholipase(s) C by calcium ions. 5. In the synaptoneurosome preparation depolarization-evoked stimulation of phosphoinositide breakdown does not involve activation of dihydropyridine-sensitive calcium channels and, instead, appears to be regulated primarily by the intracellular concentration of sodium ions. Thus, agents that induce increases in intracellular sodium--such as toxins that open or delay inactivation of voltage-dependent sodium channels; ouabain, an inhibitor of Na+/K+ ATPase that transports sodium outward and a sodium ionophore--all stimulate phosphoinositide breakdown. Mechanistically, increases in intracellular sodium either might directly affect phospholipase(s) C or might lead to influx of calcium ions through Na+/Ca2+ transporters. 6. Depolarization-evoked stimulation of cyclic AMP formation and phosphoinositide breakdown can exhibit potentiative interactions with responses to receptor agonists, thereby providing mechanisms for modulation of receptor responses by neuronal activity. 7. Since all these second messengers can induce phosphorylation of ion channels through the activation of specific kinases, it is proposed that depolarization-evoked formation of second messengers represents a putative feedback mechanism to regulate ion fluxes in excitable cells.
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PMID:Formation of second messengers in response to activation of ion channels in excitable cells. 245 43

The concentration-effect curve for the relaxant effects of glyceryl trinitrate (GTN) in rat aortic rings consisted of two phases with IC50 values of 0.1 microM for Phase I and 14 microM for Phase II. Incubation of tissues with oxyhaemoglobin or the induction of tolerance to GTN abolished responses occurring in Phase I but were without effect on Phase II relaxant responses. Both phases of the relaxant curve appeared to involve cyclic GMP since responses were (i) potentiated by the cyclic GMP phosphodiesterase inhibitor zaprinast (M & B 22948) and (ii) inhibited by methylene blue and LY83583, agents which inhibit soluble guanylate cyclase. The latter agents inhibited Phase I responses in a non-surmountable manner while Phase II responses were shifted to the right without effect on the maximal response. Neither phase of relaxation involved stimulation of the Na+/K+ ATPase pump since treatment of tissues with ouabain or K+-free solutions did not alter the GTN biphasic curve. Phase I relaxant responses to GTN resembled those to the endothelium-dependent relaxant acetylcholine, since oxyhaemoglobin and methylene blue were non-surmountable antagonists; however there was no cross tolerance to acetylcholine in GTN tolerant tissues. Phase II relaxant responses resembled those obtained with sodium nitroprusside (SNP) since neither oxyhaemoglobin nor the induction of tolerance to GTN altered the response to SNP. These results indicate that there are two distinct mechanisms of relaxation for GTN in rat aortic rings; however both mechanisms appear to involve cyclic GMP as the second messenger.
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PMID:Biphasic relaxant curves to glyceryl trinitrate in rat aortic rings. Evidence for two mechanisms of action. 256 26

PGE2 and PGA2 incubated for 30 min at 25 degrees C with microsomal membranes isolated from Walker-256 tumour, in the presence of 50 microM indomethacin increase the lipid fluidity estimated by steady-state fluorescence anisotropy [(r0/r)-1]-1, using 1,6-diphenyl-1,3,5-hexatriene (DPH) as probe. The microsomal preparations of Walker-256 tumour contained calcium-stimulated and magnesium-dependent ATPase as well as calmoduling-dependent guanylate cyclese activities. A considerable decrease (approx. 65%) in the activity of the Ca2+-stimulated ATPase was observed when preparations were treated with 10 microM PGE2 and PGA2. A dramatic gradual decrease of the calmodulin-dependent guanylate cyclase activity was also observed at different concentrations of PGE2 and PGA2 (0.25-10 microM). The ATP-dependent uptake of calcium was reduced by approximately 60% in microsomal membranes treated with PGE2 and PGA2. The allosteric properties of Ca2+-stimulated ATPase by Na+, and of guanylate cyclase by Mn.GTP (as reflected by changes in the Hill coefficients, h) were modulated by PGE2 and PGA2. The apparent cooperativity of the Ca2+-ATPase (h + 1.73 +/- 0.21) in control membranes was abolished (h + 1.1 +/- 0.11 and h = 0.9 +/- 0.09) in membranes treated by PGE2 and PGA2 (10 microM), while the allosteric stimulation of guanylate cyclase by Mn.GTP was reduced from h = 2.78 +/- 0.24 in control membranes to h = 1.92 +/- 0.16 and h = 1.73 +/- 0.15 in membranes treated by PGE2 and PGA2 (10 microM), respectively, suggesting that the physical state of Ca2+-stimulated ATPase and guanylate cyclase lipid microenvironments changed from a gel phase to a liquid-crystalline phase. In conclusion, it is suggested that PGE2 and PGA2 promote a phase separation in Walker-256 tumour microsomal membranes. This may be relevant to the Ca2+-calmodulin system and tumour growth inhibition.
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PMID:PGE2 and PGA2 affect the allosteric properties and the activities of calmodulin-dependent guanylate cyclase and Ca2+-stimulated ATPase of Walker-256 tumour microsomal membranes. 256 56

Coronary artery strips of cattle hearts in vitro respond to transmural stimulation with two potent but distinctly different responses. A neurogenic constriction, attributable to the endogenous release of acetylcholine, is predominant under conditions of minimal and moderate tone. During a high degree of spontaneous tone, and in the presence of near maximal contractions induced by 5-hydroxytryptamine, the response to field stimulation is relaxation rather than constriction. This process was studied more clearly after blockade of the cholinergic effects with atropine. The relaxation response elicited by 5 Hz stimulation for 2 min consisted of two components, one occurring during stimulation and the other promptly after its cessation. The overall relaxation was sufficient to almost obliterate a spontaneous contraction or a near-maximal contraction to 5-hydroxytryptamine. The relaxation to transmural stimulation was unaltered by tetrodotoxin, adrenergic blockade, indomethacin or 5 days cold storage of tissue. Relaxation was elicitable even by a single pulse. With a few pulses, the maximal effect was achieved at 0.5 Hz. Repeated application of three pulses, in strips with spontaneous tone, led to substantial but transient relaxations, which simulated spontaneous rhythm. Removal of the endothelium was without effect on the relaxations, and they were unaltered by inhibition of guanylate cyclase. In the presence of elevated potassium (30 mM), contractions to 5-hydroxytryptamine and those generated spontaneously did not relax to field stimulation. Inhibition of Na+-K+-ATPase with ouabain (5 microM) partially antagonized both components of the relaxation response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nonneurogenic relaxation to field stimulation in coronary arteries. 278 16

There appears to be two distinct natriuretic factors. One group, suspected since 1951 in overloaded dogs, had a low molecular weight: it belongs great affinity for ouabain, binds to digoxin antibodies and inhibits NA-K ATPase; this group seems heterogeneous in spite of the extraction of an amino glucosteroid-like substance from human urines. These factors are vasoconstrictor; the source is not still well known (hypothalamus ?). The atrial natriuretic factor (ANF) is a peptide about 20 to 25 amino acids and comes from a precursor of 152 amino acids, its synthesis was successful; secreted in the plasma from endocrine atrial granules, it causes striking natriuresis and diuresis and relaxes vascular and intestinal smooth muscle; it acts on guanylate cyclase but its renal mechanism of action is not well known; it constitutes an antagonist axe to ADH and RAA system. The relations between the two groups of natriuretic factors do not seem still very clear.
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PMID:[Natriuretic factors]. 295 21


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