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)

We recently reported that calcium ionophore A23187 causes a several-fold elevation of angiotensin converting enzyme (ACE) activity of bovine pulmonary artery endothelial cells in culture and that this elevation is dependent upon extracellular calcium. Now we have observed that monensin, a sodium ionophore, also elevates the ACE activity of these cells. This elevation in ACE was not inhibited by 0.2 mM EGTA or the calcium channel inhibitor nifedipine, and monensin did not alter intracellular calcium as measured by fluorimetric assessment of fura-2/AM-loaded cells. When confluent endothelial cells were incubated with monensin or A23187 in the presence of 10-20 nM ouabain, a specific inhibitor of Na+/K(+)-ATPase, the elevation in ACE produced by both of the ionophores was totally eliminated. Concentrations of ouabain greater than 10 nM also inhibited baseline levels of ACE activity. Ca2+ measurements of fura-2/AM-loaded cells showed that ouabain had no effect on the influx of Ca2+ produced by A23187. The elevation of ACE seemed to require new protein synthesis, since 0.1 micrograms/ml cycloheximide inhibited the elevation produced by monensin and A23187. Other sodium transport inhibitors such as amiloride or bumetanide had no effect on ACE elevation caused by monensin. These results suggest that ACE levels of bovine endothelial cells in culture are under cation regulation and may be modulated by ouabain-sensitive Na+/K(+)-ATPase.
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PMID:Elevation of bovine endothelial cell angiotensin converting enzyme by cationophores and inhibition by ouabain. 215 15

The calcium channel antagonists verapamil, gallopamil and nifedipine were tested for their effects on acid secretion stimulated by histamine and dibutyryl-cyclic AMP in isolated and enriched guinea pig parietal cells, on adenylate cyclase activity mediated by histamine H2 receptors, on histamine-stimulated increase in cytosolic-free Ca2+ concentration [Ca2+], on gastric H+/K(+)-ATPase activity and on H+/K(+)-ATPase-mediated proton uptake in intact gastric membrane vesicles. Verapamil and gallopamil impaired all cellular and enzymatic test systems studied. Both drugs affected with highest potency the acid secretion in the parietal cell preparation (IC50: 1-2 mumol/l) and the H+/K(+)-ATPase-mediated H+ uptake in gastric membrane vesicles, whereas their inhibitory action was less pronounced on adenylate cyclase and on histamine-induced increase in cytosolic-free [Ca2+]. The type of interaction found in the gastric membrane vesicle preparation indicates that both drugs act as protonophores. Nifedipine was less effective as an inhibitor of acid secretion in the parietal cell preparation and in reducing proton concentration in isolated gastric membrane vesicles. The drug failed to block adenylate cyclase and H+/K+-ATPase activity. Since nifedipine is a more effective calcium channel blocking agent but a less lipophilic drug than verapamil and gallopamil, we conclude that the antisecretory activity of calcium channel antagonists in vitro is mediated by a nonspecific, i.e. a protonophoric, action. We suggest that verapamil exhibits its antisecretory activity in vivo partially by its protonophoric action at the secretory membrane of the parietal cell, whereas the decrease in acid secretion by nifedipine is not mediated by this mechanism.
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PMID:Interaction of calcium channel antagonists with parietal cell acid production, adenylate cyclase, intracellular-free Ca2+ and H+/K+-ATPase. 215 65

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

Ryanodine binds to the transducer calcium channel complex that links depolarization of the transverse tubule to calcium release from the terminal cisternae during excitation-contraction coupling of skeletal muscle. Ryanodine exerts a bimodal action on the transducer calcium channel complex depending upon membrane potential and concentration. When the transmembrane potential is at resting level (-90 mV inside cell vs outside), low concentrations of ryanodine 10(-10) M to 10(-8) M favor calcium influx from outside which in turn causes calcium release from the terminal cisternae via calcium operated calcium channels. The leak from the terminal cisternae is insufficient to cause contraction but does cause a large increase in aerobic energy utilization by the Ca-ATPase of the sarcoplasmic reticulum. When the transmembrane potential is made more positive (-40 mV) the transducer channel is opened to the terminal cisternae of sarcoplasmic reticulum and is maintained in an open state by ryanodine allowing calcium efflux from the terminal cisternae to the sarcoplasm. At higher concentrations of ryanodine the transducer-calcium channel becomes open to the terminal cisternae and its store of ionized calcium leaks from the terminal cisternae in sufficient quantities to cause a contracture. The ryanodine-sensitive calcium transducer calcium channel operates in a bimodal manner. At low concentrations less than 10(-4) M the ryanodine-sensitive transducer calcium channel is open to the lumen of the T-tubule and allows calcium to flow in and trigger further calcium release. At higher concentrations the ryanodine-sensitive transducer channel opens to allow a calcium efflux from the terminal cisternae in sufficient quantities to cause contracture.
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PMID:Bimodal operation of the ryanodine-sensitive transducer calcium channel. 217 57

1. The effect of the calcium channel blocker nisoldipine on the myocardial content of lipid peroxidation products (malondialdehyde (MDA), conjugated double bonds (CDB), fluorescent end-products (RF) and mitochondrial adenine nucleotides) was investigated in conscious pigs (n = 14) subjected to 24 h of immobilization stress. Histoenzymatic and electron microscopic studies of the myocardium were also performed. Nisoldipine was given orally in a twice daily dose of 20 mg for 2 days before and on the day of the experiment. Results were compared with those obtained in immobilized untreated pigs (n = 10) and in non-stressed treated controls (n = 8). 2. Pretreatment with nisoldipine significantly attenuated stress-induced increase in myocardial contents of CDB and RF and prevented decline of mitochondrial adenine nucleotides. Stress-induced myocardial histoenzymatic changes (decrease of succinic dehydrogenase, ATPase, acid phosphatase activity) and ultrastructural alterations (mitochondrial damage, lysis of myofibrils, dilatation of sarcoplasmic reticulum and endothelial swelling) were also diminished. 3. It is concluded that treatment with a Ca2(+)-antagonist is beneficial to the heart exposed to environmental stress.
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PMID:Effect of nisoldipine on stress-induced myocardial damage in the conscious pig. 235 Sep

A cell line originating from the fetal rat aorta has been studied with respect to 45Ca2+ uptake. Kinetic experiments showed an initial rapid uptake followed by a slow linear phase; both the initial rate and the maximum uptake were increased in the presence of 55 mM potassium chloride. The calcium channel antagonists, darodipine (PY 108-068) and verapamil, inhibited both the basal and the potassium chloride stimulated uptake. Neither tetrodotoxin nor furosemide affected either basal or depolarisation induced 45Ca2+ uptake. Blockade of the Na+/K+ ATPase by ouabain and of the Ca2+ ATPase by vanadate caused a net increase in cellular 45Ca2+ accumulation.
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PMID:A smooth muscle cell line suitable for the study of voltage sensitive calcium channels. 241 Dec 61

The cardiovascular effects of different calcium channel blockers (CCB), exemplified by nifedipine, verapamil and diltiazem, are not identical. Some of these differences in effect may be due to the different CCBs interacting with different calcium channel subtypes in the tissues, and/or that the drug-receptor sites are separate. The drugs also have different abilities to activate the sympathetic nervous system, nifedipine increasing and diltiazem decreasing the baroreflex sensitivity. Verapamil, but not nifedipine and diltiazem, has a postjunctional alpha-adrenoceptor blocking effect, and can also increase the release of noradrenaline from adrenergic nerves by blocking pre-junctional alpha-adrenoceptors. In addition, verapamil may have a reserpine-like action on sympathetic nerves. The vasodilator actions of CCBs are not uniform, but seem to vary between species, different vascular regions, and different agents. Mechanisms other than blockade of influx of calcium from the extracellular medium have been suggested to explain these differences, including inhibition of intracellular calcium release, blockade of postjunctional alpha-adrenoceptors, interaction with calmodulin, inhibition of cyclic AMP phosphodiesterase, stimulation of Na+-, K+-activated ATPase, stimulation of a calcium pump, and a direct interaction with the contractile proteins. The heterogeneity in pharmacodynamic profile characterizing the CCBs is conspicuous, and may be of importance when selecting agents for the treatment of various cardiovascular and non-cardiovascular disorders.
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PMID:Pharmacodynamic profiles of different calcium channel blockers. 242 67

The effects of morphine sulfate on rectal temperature and on Ca++-stimulated Mg++ATPase activity in crude synaptosomal fraction (P2) of cortex, hypothalamus and cerebellum were investigated in rat. Morphine (3-15 mg/kg, SC) produced hyperthermia at 30-120 min after the drug administration. The Ca++/Mg++ ATPase activity in hypothalamus and cortex was decreased while there was no change in Mg++ ATPase activity. The enzyme activity in cerebellum was not affected. The opiate antagonist naloxone hydrochloride (5 mg/kg, SC) antagonized the effect of morphine on rectal temperature and Ca++/Mg++ ATPase activity. The effects of different calcium channel antagonists (nimodipine 1 mg/kg, verapamil 2.5 mg/kg and diltiazem 10 mg/kg, SC) on the changes induced by morphine were also investigated. These antagonists not only antagonized morphine hyperthermia, but also the inhibitory effect of morphine on Ca++/Mg++ ATPase activity in hypothalamus. The calcium channel agonist BAY K8644 (3 mg/kg, SC) produced hypothermia and also stimulation of Ca++/Mg++ ATPase activity in hypothalamus. Naloxone failed to alter these effects of BAY K8644. These studies demonstrate that Ca++ transport in hypothalamus, as indicated by Ca++/Mg++ ATPase activity, plays an important role in thermoregulation and thermoregulatory changes induced by opiates.
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PMID:Opiate receptor mediated hyperthermic responses in rat following Ca++ channel antagonists. 243 Mar 6

The Ca2+ antagonist binding sites associated with the voltage dependent calcium channel in rabbit myocardium were found to distribute with the sarcolemmal Na+ + K+ ATPase and adenylate cyclase activities during subcellular fractionation on sucrose-density gradients. The equilibrium dissociation constants (KD) for the binding of [3H]nitrendipine and [3H]verapamil were 0.31 +/- 0.04 nM and 4.1 +/- 0.5 nM respectively, and displayed an average density of 0.55 +/- 0.05 pmol/mg and 0.4 +/- 0.03 pmol/mg protein respectively for the most enriched membrane fraction. The Ca2+ antagonist binding sites were solubilized from the membranes with the detergent 3-[(3-cholamidopropyl)dimethylammonio]propanesulfonate, and specific binding sites for [3H]PN200-110, [3H]verapamil and [3H]diltiazem were isolated on a wheat-germ lectin column. The binding sites for [3H]PN200-110 were enriched about 2,500 fold as compared with the original homogenate and displayed a density of 28.5 +/- 8 pmole/mg protein in the isolated fraction. Sodium dodecyl sulfate gel electrophoresis of the isolated drug binding proteins indicated enrichment of proteins of Mr 170,000, 140,000, 130,000, 100,000 and 53,000. The isolated receptor contained an intrinsic kinase activity that phosphorylated glycoproteins of Mr 170,000 and 53,000. Exogenously added cAMP-kinase stimulated phosphorylation of the 170,000, 100,000, 53,000 and 28,000 Mr glycoproteins in the receptor fraction. The results of this study indicate that the binding sites for [3H]nitrendipine, [3H]PN200-110, [3H]verapamil and [3H]diltiazem residue on glycoprotein(s) which are of sarcolemmal origin, and co-purify together on wheat germ lectin columns. The polypeptide composition of the Ca2+ antagonist binding sites from cardiac muscle appears to be very similar to that of the dihydropyridine receptor in skeletal muscle.
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PMID:Subcellular distribution and isolation of the Ca2+ antagonist receptor associated with the voltage regulated Ca2+ channel from rabbit heart muscle. 244 72

Activation of the low affinity Ca-ATPase and Ca-ADPase by increasing concentrations of their cationic cofactor calcium (0.1-8.0 mmol.l-1) or by increasing concentration of substrates ATP or ADP (0.1-8.0 mmol.l-1) was influenced on similar mode by sodium azide. Kinetic analysis of the NaN3 induced inhibition, revealed that both enzyme activities are probably secured by the same system which is capable to hydrolyze ADP during the absence of ATP. A possible role for Ca-ADPase in controlling the calcium channel during ATP deficiency is discussed.
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PMID:Ca-dependent ADPase--the possible regulator of calcium channel during the deficiency of ATP. 244 85


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