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)

This study examined the effect of parathyroid hormone (PTH) on myocardial energy production, transfer, and utilization. Rats (150 to 200 g) were injected with 1-84 PTH, 200 U/day i.p., or 1-34 PTH, 200 or 300 U/day i.p., for 4 days. Control animals received the vehicle only. The effect of the simultaneous administration of calcium channel blocker, verapamil, was also examined. Myocardial contents of Pi, ATP, and CP were significantly (P less than 0.01) lower in the 1-84 PTH-treated rats than in control animals. Both 1-84 PTH and 1-34 significantly (P less than 0.01) reduced mitochondrial oxygen consumption without altering ADP:O ratio indicating reduced phosphorylation. 1-84 and 1-34 PTH significantly (P less than 0.01) reduced the activities of mitochondrial and myofibrillar creatine phosphokinase and 1-84 PTH inhibited (P less than 0.01) the activities of mitochondrial Mg ATPase and those of myofibrillar Ca ATPase. There were significant (P less than 0.01) increments in myocardial 45Ca and in total calcium content in 1-84 PTH-treated rats. Verapamil abolished all the effects of 1-84 PTH. Similarly, inactivation of 1-84 PTH abolished its effects. Treatment with 1-84 PTH for 10 days was associated with a significant decrease in cardiac index and mean arterial pressure. Our data demonstrate that both 1-84 and 1-34 PTH impair energy production, transfer, and utilization. These biochemical derangements, if maintained, produce a decrease in cardiac index. It appears that the enhanced entry and the accumulation of calcium in the myocardium, either directly and/or indirectly, are responsible for the action of PTH on energy metabolism of the heart.
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PMID:Effect of parathyroid hormone on myocardial energy metabolism in the rat. 316 Aug 82

Resistance of human cancer cells to multiple cytotoxic hydrophobic agents (multidrug resistance) is due to overexpression of the "MDR1" gene, whose product is the plasma membrane P-glycoprotein. Plasma membrane vesicles partially purified from multidrug-resistant human KB carcinoma cells, but not from drug-sensitive cells, accumulate [3H]vinblastine in an ATP-dependent manner. This transport is osmotically sensitive, with an apparent Km of 38 microM for ATP and of approximately equal to 2 microM for vinblastine. The nonhydrolyzable analog adenosine 5'-[beta, gamma-imido]triphosphate does not substitute for ATP but is a competitive inhibitor of ATP for the transport process. Vanadate, an ATPase inhibitor, is a potent noncompetitive inhibitor of transport. These results indicate that hydrolysis of ATP is probably required for active transport of vinblastine. Several other drugs to which multidrug-resistant cell lines are resistant inhibit transport, with relative potencies as follows: vincristine greater than actinomycin D greater than daunomycin greater than colchicine = puromycin. Verapamil and quinidine, which reverse the multidrug-resistance phenotype, are good inhibitors of the transport process. These results confirm that multidrug-resistant cells express an energy-dependent plasma membrane transporter for hydrophobic drugs, and establish a system for the detailed biochemical analysis of this transport process.
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PMID:ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells. 336 66

Inhibition of renin secretion from incubations of rat kidney cortex by angiotensin II (AII), ouabain and K+ depletion, depended on the presence of external Ca2+. AII inhibition of isoprenaline-stimulated renin secretion was only partially dependent on external Ca2+. Ouabain and K+ depletion inhibited isoprenaline-stimulated renin release but only in the presence of external Ca2+. Since, in Ca2+-free medium, isoprenaline stimulated renin release when the Na+/K+-ATPase was blocked, isoprenaline probably does not act through the Na+/K+-ATPase. Lanthanum blocked the stimulation of renin release by isoprenaline. Ethylenediamine tetra-acetic acid (EDTA) and ethyleneglycol-bis-(beta-amino-ethyl ether) N,N'-tetra-acetic acid (EGTA) increased renin secretion to a similar degree in Ca2+- and Mg2+-free buffer. When Mg2+ was present the effect of EGTA, but not EDTA, was considerably reduced. Verapamil reduced the fall in basal renin secretion in normal but not Ca2+-free buffer. Verapamil did not block the inhibitory effects of AII or ouabain and did not alter the stimulation of renin secretion by isoprenaline. Bay K 8644 inhibited renin secretion from cortex incubated in medium containing 15 mM K+ and this was dependent on extracellular Ca2+. In normal buffer (5.9 mM K+) Bay K 8644 increased renin secretion.
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PMID:Stimulation and suppression of renin release from incubations of rat renal cortex by factors affecting calcium flux. 354 5

Increases in intracellular Na+ concentration ([Na+]i) lead to an increase in the number of Na+ pump sites in the cell membrane. To investigate further the role of [Na+]i in the regulation of Na+-K+-ATPase sites, we studied the effect of reduced [Na+]i on the number of Na+ pump sites and Na+-K+ pump activity using spontaneously beating cultured chick ventricular cells. Cells incubated in medium containing 60, 80, 100, or 140 mM Na+ for 24 or 48 h showed an extracellular [Na+]-dependent alteration in cellular Na+ content. The number of Na+ pump sites identified by [3H]ouabain binding binding declined with decreasing levels of Na+ in the medium in a time-dependent manner over 48 h, with a concomitant increase in cellular Na+ content. Verapamil (1 microM) or tetrodotoxin (1 microM) significantly reduced cellular Na+ content by 30 min of exposure and the number of Na+ pump sites by 48 h of incubation. Na+ pump activity determined from the ouabain-sensitive 42K+ uptake rate was significantly reduced in cells grown in low Na+ for 48 h, as was pump capacity, determined in Na+-loaded cells. These results support the view that [Na+]i exerts a long-term modulating effect on the number of physiologically functional Na+ pump sites.
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PMID:Effect of growth in low-Na+ medium on transport sites in cultured heart cells. 394 6

The monovalent cationic ionophores monensin and nigericin stimulated rapid guinea pig sperm acrosome reactions in the presence of extracellular Na+, Ca2+ and bicarbonate (HCO3-/CO2). Extracellular K+ (mM concentrations), in contrast, was not required for the stimulatory effect of the ionophores. The effect of HCO3-/CO2 is concentration, pH and temperature dependent, with maximal responses obtained with 50 microM monensin or 25 microM nigericin at a concentration of 30 mM HCO3-, 2.5% CO2 and pH 7.8 at 25 degrees C. At a constant HCO3- concentration (30 mM), monensin stimulated acrosome reactions within the pH range 7.5-7.8, whereas a higher or lower pH did not support acrosome reactions at 25 degrees C. At constant extracellular pH (7.8), monensin stimulated acrosome reactions in the presence of 30 mM HCO3-, whereas higher and lower concentrations did not support acrosome reactions at 25 degrees C. The permeant anions pyruvate and lactate were essential to maintain sperm motility when treated with monensin under these conditions. NH4Cl, sodium acetate and 4,41-diisothiocyano-2, 21-disulfonic acid stibene (DIDS; 25 microM), an anion transport inhibitor, blocked the ability of monensin to stimulate acrosome reactions. Verapamil (100 microM), a putative Ca2+ transport antagonist, in contrast, did not prevent the monensin-induced acrosome reactions. Physiological concentrations of Na+ were needed for monensin to stimulate acrosome reactions, but high concentrations of Mg2+ prevented the monensin stimulation. The Ca2+ ionophore A23187 (75 nM) also required physiological concentrations of Na+ for the rapid induction of maximal acrosome reactions at an elevated pH (8.3) but did not require the presence of extracellular HCO3-. These studies suggest that a monovalent ionophore-induced rise in sperm intracellular Na+ concentrations is a pre-Ca2+ entry event, that stimulates an endogenous Ca2+/Na+ exchange that allows a Ca2+ influx which in turn induces the acrosome reaction. The possible regulatory role of the sperm intracellular pH and Na+, K+-ATPase during the capacitation process under physiological conditions is discussed.
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PMID:Bicarbonate- and calcium-dependent induction of rapid guinea pig sperm acrosome reactions by monovalent ionophores. 608 22

Effect of verapamil on the organic acid transport was examined with rat kidney cortical slices. Verapamil increased the initial rate of p-aminohippurate (PAH) uptake, markedly enhanced its maximal accumulation under steady-state conditions and depressed the efflux of PAH. The accumulation of urate was also stimulated by verapamil. D600, a derivative of verapamil, showed the same effect as verapamil with regard to the stimulation of PAH accumulation. Kinetic studies revealed that verapamil resulted in an increase in the Vmax of the transport of PAH. The apparent Km remained essentially constant. The PAH accumulation was enhanced by aerobic preincubation of the slices with verapamil at 37 degrees C. On the other hand, the preincubation of the slices with verapamil at 0 degrees C did not alter the PAH accumulation. Oxygen consumption and ATP content in the slices and microsomal (Na+ + K+)adenosine triphosphatase activity were not affected by verapamil. Verapamil enhanced a Na+ gradient to some degree. however, the PAH accumulation in the presence of verapamil and ouabain was increased approximately the same amount as in the absence of these drugs regardless of the dissipation of the Na+ gradient by ouabain. These results suggest that verapamil accumulated by the slices stimulates the PAH uptake and its stimulatory action cannot be explained by the increase in the Na+ gradient and stimulation of (Na+ + K+)adenosine triphosphatase activity.
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PMID:Stimulatory action of verapamil on transport of organic acids in rat kidney cortical slices. 621 70

In isolated and enriched guinea pig parietal cells the inhibitory effects of the calcium channel antagonists verapamil and gallopamil on 14C-aminopyrine uptake (= H+ secretion) have been analyzed. Both verapamil and gallopamil inhibit acid secretion in a concentration-dependent manner with an IC50 of 12.1 and 10.9 mumol/l respectively. The type of inhibition is noncompetitive in nature. Verapamil inhibits the acid response to histamine, dibutyryl-cAMP, and KCl with IC50 values not significantly different from each other. Exposure of the cells to verapamil and subsequent washing enhances the acid response to histamine for an unknown reason. It is concluded that the calcium channel antagonists verapamil and gallopamil inhibit acid secretion in vitro by interfering with the parietal cell proton pump, the K+/H+-ATPase.
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PMID:Calcium channel antagonists verapamil and gallopamil are powerful inhibitors of acid secretion in isolated and enriched guinea pig parietal cells. 631 Jun 46

The effects on in vitro renin release from rat kidney cortex of various agents which are thought to alter intracellular Ca were investigated. Incubation in Ca-free medium had no effect on basal or isoprenaline-stimulated renin release, but the addition of EDTA stimulated renin release. Angiotensin II (ANG II) and ouabain both inhibited basal and isoprenaline-stimulated renin release, and external Ca was important in this effect. Verapamil reduced the fall in basal renin release and the inhibitory effect of ANG II. In addition, verapamil blocked the inhibition by ANG II, but not by ouabain, of isoprenaline-stimulated renin release. Isoprenaline may stimulate the Na,K-ATPase leading to increased Ca efflux via Na-Ca exchange, whereas ouabain may have the opposite effect. ANG II probably stimulates Ca influx and release from intracellular stores.
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PMID:The role of calcium in the control of renin release. 644 9

1 The effect of (+/-)-, (+)- and (-)-verapamil on the Ca2+-binding, Ca2+-transporting activity, and Ca2+-dependent adenosine triphosphatase (ATPase) activity of isolated cardiac sarcolemmal preparations was studied. Enzymatic treatment was used to establish the nature of the sites facilitating [14C]-(+/-)-verapamil binding. 2 (+/-)-Verapamil 1 microM inhibited the passive binding of 45Ca2+. The (+/-)- and (-)-isomers were equiactive. 3 (+/-)-Verapamil 1 microM inhibited the ATP-dependent transport of 45Ca2+ and the associated activation of the Ca2+-sensitive ATPase. The activity resided in the (-)-isomer. 4 Lineweaver-Burk plots for the initial rates of ATP-dependent transport showed that the inhibition induced by the (-)-isomer was accompanied by a reduced Km and Vmax. 5 Enzymatic removal of N-acetyl neuraminic acid and galactose residues increased [14C]-(+/-)-verapamil binding; removal of N-acetylglucosamine and treatment with phospholipase C and trypsin decreased the binding. 6 These results have been interpreted to mean that (-)-verapamil interferes with the ATP-dependent Ca2+-transporting properties of the sarcolemma, and that this effect is accompanied by an altered activity of the intrinsic Ca2+-sensitive ATPase. N-acetylneuramic acid and galactose residues do not provide binding sites for verapamil at the cell surface.
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PMID:The effect of verapamil on the Ca2+-transporting and Ca2+-ATPase activity of isolated cardiac sarcolemmal preparations. 645 Dec 52

Taurine (2-aminoethane sulfonic acid) is found in high concentrations in the heart, particularly in Purkinje fibers. We studied the transport of taurine in Purkinje fibers that were excised rapidly from the heart and placed in a vessel containing oxygenated Krebs-Henseleit solution (37 degrees C). After equilibration, 4.4 x 10(-6)M radiolabeled taurine[14C] was added to the bath. A computer compartmental analysis of the uptake and efflux indicated the presence of two pools for uptake--a pool with a rapid kinetics K1 (t1/2 = 0.80 min) and K2 (t1/2 = 176.30 min). These studies suggest that Purkinje fibers have the capacity to transport taurine rapidly. Michaelis-Menten procedures showed the presence of a high affinity and a low affinity transport process. Guanidinotaurine, at a 10:1 ratio, had no appreciable effect on taurine uptake, but 3-aminopropane phosphonic acid decreased taurine uptake by 42.7%. Ouabain and acetylstrophanthidin (10(-5) M) inhibited taurine uptake (K1) by 34% and 73%, respectively. The inhibition of the rapid component of taurine uptake suggests that K1 is an energy-linked process possibly requiring Na+,K+-ATPase. Taurine uptake in a calcium-free medium was decreased by 58%. Verapamil (6 x 10(-6) M) decreased taurine uptake by 42%. Tetrodotoxin (3.4 x 10(-5) M) decreased taurine uptake by 51%. The requirement of calcium and sodium for taurine uptake suggests an important relationship between taurine, calcium, and sodium in the function of fibers in the cardiac conducting system.
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PMID:Pharmacokinetic studies of taurine in bovine Purkinje fibers. 741 33


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