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)

1. The mechanisms of K+ secretion into endolymph were studied on a preparation of isolated semicircular canal with different pharmacological inhibitors. Three periods of 5 or 30 min were performed, the first as control, the second in the presence of the drugs added to the apical or the basolateral bathing solution, and the third as recovery. Apical fluid was sampled at the beginning and the end of each period, transepithelial potential was recorded, Na+, K+, and Cl- concentrations, and K+ efflux, with 86Rb+ as a tracer, were measured and K+ fluxes were calculated. 2. When both sides of the epithelium were bathed with perilymph-like solution, the epithelium absorbed Na+, secreted K+, and generated a lumen positive potential. 3. The ATPases inhibitors, ouabain (10(-5) and 10(-3) M) and N-ethylmaleimide (10(-4) and 10(-3) M) inhibited the electrogenic K+ secretion when added to the basolateral fluid. N-ethylmaleimide (10(-3) M) applied to the apical fluid during a 5 min period decreased the K+ influx by 43% and the transepithelial potential by 66%. Other ATPase inhibitors, harmaline (10(-3) M), omeprazole (10(-4) M), vanadate (10(-4) M and 10(-3) M), N,N'-dicyclohexylcarbodiimide (DCC, 10(-5) M), 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-Cl, 5 x 10(-6) M and 5 x 10(-5) M), and bafilomycin (10(-7) M) did not affect the K+ transport nor the transepithelial potential when they were added to the apical fluid. 4. The Na(+)-K(+)-Cl- co-transporter inhibitor, bumetanide, decreased both the transepithelial potential and the K+ transport when added to the basolateral solution but not to the apical one. At 10(-6) M, bumetanide maximally decreased the K+ influx by about 60%. 5. K+ channel blockers, quinine (10(-4) M), TEA (5 x 10(-3) M), added to the apical solution and barium (2 x 10(-3) M) added to either the apical or the basolateral solutions, did not affect the K+ transport and the transepithelial potential. 6. The carbonic anhydrase inhibitor acetazolamide (10(-3) M) added to both apical and basolateral solutions did not affect the K+ transport and the transepithelial potential. 7. It is concluded that, in the ampulla of the semicircular canal, a basolateral Na(+)-K(+)-Cl- co-transporter energized by the Na+, K(+)-ATPase was involved for 60% in the K+ secretion into endolymph. The electrogenic K+ transport would partly depend on a N-ethylmaleimide-sensitive protein possibly located at the apical plasma membrane or intracellularly.
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PMID:N-ethylmaleimide-inhibited electrogenic K+ secretion in the ampulla of the frog semicircular canal. 839 25

The purpose of this study was to determine the roles of extracellular cations (Na+, Ca2+ and K+), membrane K+ channels and Na+/K+ ATPase in the development of myogenic contraction (transmural pressure-induced contraction) in isolated rat skeletal muscle and mesenteric small arteries. The vessels were pressurized under no-flow conditions in a tissue bath. Lumen diameter was measured with a videomicroscopic system. Myogenic contraction was evoked by increasing the lumen pressure from 40 to 100 mmHg. The vessels demonstrated myogenic contraction in low-Na+ (Na+ 1.18 mmol/L) physiological salt solution (PSS), and this was abolished by removing Ca2+ or by applying nifedipine or nisoldipine (10 mumol/L). Neither tetraethylammonium (TEA, 1 mmol/L), Ba2+ (10 mumol/L) nor glibenclamide (1 mumol/L) affected the magnitude of the myogenic contraction. K(+)-free PSS and ouabain (0.1 mmol/L) partially depressed myogenic contraction. In conclusion, myogenic contraction was triggered by a cellular process that requires extracellular Ca2+, but not Na+ or K+. This triggering process is not affected by TEA, Ba2+ or glibenclamide.
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PMID:The role of extracellular cations in the development of myogenic contraction in isolated rat small arteries. 872 72

1. An apamin-sensitive Ca(2+)-activated K+ channel was characterized in turtle hair cells and utilized to monitor submembranous intracellular Ca2+ and to evaluate the concentration of the mobile endogenous calcium buffer. 2. Isolated hair cells were voltage clamped with whole-cell patch electrodes filled with a Cs(+)-based intracellular solution to block the large-conductance Ca(2+)-activated K+ (BK) channel. Ca2+ currents evoked by depolarization were followed by inward tail currents lasting several hundred milliseconds. Both the Ca2+ current and slow tail current were abolished by nifedipine. 3. The tail current was carried by K+ and Cs+ (relative permeabilities PCa/PK = 0.22), and was fully blocked by 0.1 microM apamin and half blocked by 5 mM external TEA. These properties suggest the tail current flows through a Ca(2+)-activated K+ channel distinct from the BK channels. 4. Intracellular Ca2+ was imaged with a confocal microscope in hair cells filled with the indicator Calcium Green-5N introduced via the patch pipette. Increases in Ca2+ evoked by depolarization were localized to hotspots on the basolateral surface of the cell. The time course of the tail current closely matched the fast component of the fluorescenece monitored at a hotspot. 5. Ca(2+)-ATPase pump inhibitors thapsigargin, 2,4-di-(t-butyl)hydroquinone (BHQ) and vanadate, which are known to influence calcium regulation in turtle hair cells, prolonged the time course of the tail current, supporting the idea that the channel monitors cytoplasmic Ca2+. 6. The mobile endogenous buffer was estimated by combining perforated-patch and whole-cell recordings on a single cell. After recording tail currents with an amphotericin-perforated patch, the patch was ruptured to obtain the whole-cell mode, thus allowing washout of soluble cytoplasmic proteins and exchange with pipette buffers. By varying the concentration of Ca2+ buffer in the pipette, the mobile endogenous buffer was found to be equivalent to about 1 mM BAPTA.
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PMID:Monitoring calcium in turtle hair cells with a calcium-activated potassium channel. 886 61

1. The aim of this study was a pharmacological characterization of the multiple NANC inhibitory transmission systems producing relaxation of the circular muscle of guinea-pig proximal colon. In the presence of atropine (1 microM), guanethidine (3 microM) and of the tachykinin NK1 and NK2 receptor antagonists, SR 140333 (0.3 microM) and MEN 10627 (1 microM), respectively, electrical field stimulation (EFS) produced a frequency-dependent (0.1-3 Hz) relaxation. During a cumulative frequency-response curve, the maximal relaxant effect was produced at 3 Hz and approached the maximal relaxation to 1 microM isoprenaline. In the presence of both apamin (0.3 microM) and L-nitroarginine (L-NOARG, 100 microM), EFS failed to evoke relaxation up to 1 Hz; at 1-10 Hz, a slowly developing relaxation ensured which approached 50% of the Emax to isoprenaline. The EFS-evoked NANC relaxation, either in the presence or absence of apamin and L-NOARG, was unaffected by in vitro capsaicin pretreatment (10 microM for 15 min). 2. Three protocols of EFS were developed for further pharmacological analysis: (a) EFS at 1 Hz for 5 s in the presence of L-NOARG, producing a transient fast apamin-sensitive relaxation; (b) EFS at 1 Hz for 5 s in the presence of apamin, producing a transient fast L-NOARG-sensitive relaxation; and (c) EFS at 10 Hz for 5 s in the presence of both apamin and L-NOARG, producing a transient but slowly developing and more sustained relaxation. 3. The neutral endopeptidase inhibitor, thiorphan (1-10 microM), enhanced and prolonged the apamin- and L-NOARG-resistant NANC relaxation produced by EFS at 10 Hz, without affecting that evoked at 1 Hz in the presence of apamin or L-NOARG. The angiotensin converting enzyme inhibitor, captopril (1-10 microM) was without effect. 4. The cAMP analogue inhibitor of protein kinase A, Rp-cAMPs (100-300 microM) significantly reduced and shortened the NANC relaxation produced by 10 Hz EFS in the presence of L-NOARG without affecting that produced by 1 Hz EFS in the presence of apamin or L-NOARG. 5. The inhibitor of sarcoplasmic reticulum Ca-ATPase, cyclopiazonic acid (CPA, 3-10 microM for 60 min) abolished the 1 Hz EFS-induced relaxation in the presence of L-NOARG, and greatly inhibited that produced by 10 Hz EFS in the presence of both apamin and L-NOARG. The relaxation produced by 1 Hz EFS in the presence of apamin was inhibited by about 32% at 10 microM only. 6. Nifedipine (1 microM) did not affect the EFS-induced NANC relaxations. In the presence of nifedipine, tetraethylammonium (TEA, 1 mM) enhanced the 1 Hz EFS-induced relaxation in the presence of L-NOARG (158% of control) and that produced by 10 Hz EFS in the presence of apamin and L-NOARG (215% of control) while that evoked by 1 Hz EFS in the presence of apamin was slightly affected (109% of control). 7. In the presence of atropine, guanethidine, SR 140333 and MEN 10627, bath application of human vasoactive intestinal polypeptide (VIP, 0.1 nM-10 nM) produced a concentration-dependent, slowly developing relaxation of colonic strips. The relaxation to VIP was unaffected by apamin (0.3 microM), L-NOARG (100 microM), nifedipine (1 microM) or nifedipine plus TEA (1 mM); it was inhibited by CPA (10 microM) and Rp-cAMPs (100 microM) and was potentiated by thiorphan (10 microM). 8. The putative VIP receptor antagonist, VIP(10-28) (10 microM) did not affect the VIP-induced relaxation nor the NANC relaxation to 10 Hz EFS in the presence of apamin and L-NOARG. 9. The present findings provide evidence that three distinct NANC inhibitory mechanisms mediate relaxation of the circular muscle of the guinea-pig proximal colon. The first system provides a fast relaxation in response to low frequency of stimulation and may involve the action of a transmitter(s) (possibly ATP) which mobilizes intracellular Ca2+ from sarcoplasmic reticulum leading to the activation of apamin-sensitive K+ channels. The second system likewise provides a fast relaxation of the colon in
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PMID:Characterization of the apamin- and L-nitroarginine-resistant NANC inhibitory transmission to the circular muscle of guinea-pig colon. 888 60

Cyclopiazonic acid (selective blocker of the internal Ca+2 pump) evoked tonic contraction in canine bronchial smooth muscle (BSM) and tracheal smooth muscle. This contraction was biphasic, including an initial component that was relatively insensitive to blockade of Ca+2 influx (e.g., removal of external Ca+2; nifedipine; hyperpolarization using lemakalim) followed by a component that was sensitive to all such interventions. In BSM, but not in tracheal smooth muscle, electrical field stimulation (EFS) evoked relaxations that were not affected by interventions designed to prevent release of autacoids from nerve endings or the epithelium, Na+/Ca+2 exchange or Ca(+2)-ATPase activities (internal or plasmalemmal). EFS evoked little or no relaxant response in carbachol-precontracted BSM in the presence of propranolol. After Ca+2 was replaced with Sr+2, however, carbachol evoked comparable contraction after which EFS evoked non-neurogenic relaxations. We found that the EFS-evoked relaxations were abolished by TEA or high KCI, were reduced significantly by charydotoxin or quinine, were reduced partially by ouabain and were unaffected by removal of external K+, by apamin or by glybenclamide. In addition, the relaxations were reduced significantly by the free radical scavenger N-acetylcysteine, were mimicked by H2O2 but were unaffected by superoxide dismutase or catalase. These observations suggest that the cyclopiazonic acid-evoked contraction involves pharmacomechanical coupling mechanisms (i.e., Ca(+2)-release) initially, followed by electromechanical coupling (i.e., voltage-dependent Ca+2 influx). After depletion of the internal Ca+2 store (e.g., by cyclopiazonic acid or Sr+2), EFS is able to evoke in BSM (but not in tracheal smooth muscle) relaxations that seem to involve opening of K+ channels (including those of the large-conductance Ca(+2)-dependent type) by EFS-liberated free radicals.
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PMID:Non-neurogenic electrically evoked relaxation in canine airway muscle involves action of free radicals on K+ channels. 893 Jan 88

This study was undertaken to examine if modulations of intracellular and extracellular Ca2+ affect the lethal cell injury and impairment of membrane transport function induced by oxidants in rabbit renal cortical slices. The oxidant t-butylhydroperoxide (t-BHP) and H2O2 increased lactate dehydrogenase (LDH) release and inhibited PAH uptake in a dose-dependent manner, but the potency of H2O2 was 100 times lower than that of t-BHP. Catalase prevented the effect of H2O2 but not that of t-BHP, suggesting that lower potency of H2O2 is attributed to the endogenous catalase activity. t-BHP induced lipid peroxidation and inhibited microsomal (Na+)-(K+)-ATPase activity. Omission of Ca2+ from the medium or addition of Ca2+ channel blockers (verapamil, diltiazem, and nifedipine) prevented the oxidant-induced LDH release. Similar effect was observed by addition of La3+. Buffering intracellular Ca2+ with BAPTA/AM decreased the oxidant-induced LDH release. However, the oxidant-induced impairment in PAH uptake was not altered under the same conditions. Also, the inhibition of microsomal (Na+)-(K+)-ATPase activity by t-BHP was not affected by verapamil, La3+, and BAPTA/AM. Dithiothreitol and glutathione prevented the oxidant-induced LDH release and reduction of PAH uptake and impeded the oxidant-induced inhibition of (Na+)-(K+)-ATPase activity and lipid peroxidation. Effects of t-BHP on TEA uptake were similar to those on PAH uptake. Modulations of intracellular or extracellular Ca2+ had little effect on the oxidant-induced lipid peroxidation. Glycine did not exert protective effect against the oxidant-induced cell injury. These results suggest strongly that Ca2+ plays an important role in the oxidant-induced LDH release but not in the oxidant-induced alterations of membrane transport function in rabbit renal cortical slices. The role of Ca2+ in oxidant-induced LDH release is not apparently associated with peroxidation of membrane lipid.
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PMID:Differential effect of Ca2+ on oxidant-induced lethal cell injury and alterations of membrane functional integrity in renal cortical slices. 897 86

Rhythmic contractions are produced by small arteries, arterioles and veins in several vascular beds, but they are often absent in large arteries. However, under certain conditions, and in certain disease states large arteries may produce rhythmic contractions. For this reason, the present study was undertaken to test the hypothesis that rhythmic contractions may be a 'normal' response in large arteries at some stage in development. We investigated this hypothesis by examining contractions of carotid arteries in male and female rats aged 15, 25 and 30 days and in adult rats. Rhythmic contractions were produced by exposure to, or during washout of alpha-adrenoceptor agonists in young, but not adult, rats. In particular, rhythmic activity was identified in 40, 95 and 50% of the arteries from, respectively, 15, 25 and 30-day-old rats. No differences were found in rhythmic activity between female and male rats. Furthermore, the rhythmic activity was not inhibited by the K+ channel blocker TEA (20 mM) or the Na+/K(+)-ATPase inhibitor, ouabain (32 microM). Nor was it inhibited by endothelial denudation. However, the Ca2+ channel blocker, nifedipine (0.1 microM), completely eliminated rhythmic contraction. These results suggest that receptor-induced rhythmic contractile activity is a 'normal' characteristic at approximately 25 days of development in carotid arteries of rats, but that this activity declines with age until it is completely absent by adulthood. We proposed that this difference was due to unfused and fused Ca2+ channel activities in, respectively, young and adult rat arteries, to differential expression of Ca2+ channel isotypes, or to differences in receptor-mediated signal transduction mechanisms 'upstream' from Ca2+ channels.
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PMID:Alpha-adrenoceptor activation induces rhythmic contractile activity in carotid arteries from young, not adult, rats. 905 39

In canine airway smooth muscle, cyclopiazonic acid (CPA; selective blocker of the sarcoplasmic reticulum Ca(2+)-pump) evokes a contractile response which is initially mediated via release of internally sequestered Ca2+, but is later supported almost exclusively by electromechanical coupling. As such, this second component is highly sensitive to inhibition of voltage-dependent Ca(2+)-influx (e.g. dihydropyridines, removal of external Ca2+) or to membrane hyperpolarization. In the present study, we describe relaxations which occur spontaneously during this second component of the CPA-evoked contraction. These relaxations are also electromechanically mediated, since they are abolished by depolarization of the membrane by high-K+ media. TEA has relatively little effect on the phasic activity, thus ruling out an involvement of Ca(2+)-dependent K+ channels. On the other hand, the phasic activity is abolished by ouabain, by removal of external K+, or by cooling and is markedly slowed by removal of external Na+. These observations indicate that the phasic activity is mediated by the Na+/K(+)-ATPase.
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PMID:Na+/K+ ATPase mediates rhythmic spontaneous relaxations in canine airway smooth muscle. 923 92

1. The present study examined the effects of various agents on high calcium-induced relaxation of the rabbit thoracic aorta precontracted by phenylephrine (0.1 microM) or KCl (30 mM). 2. The vascular smooth muscle relaxation caused by high calcium was not changed in the presence of endothelium, glibenclamide (3 microM), TEA (5 mM), verapamil (1 microM), lidocaine (0.1 mM) and vanadate (0.1 mM). 3. In the presence of ouabain (0.1 mM) or potassium-free medium, high calcium-induced relaxation was completely abolished. 4. When rings were precontracted by high concentrations of phenylephrine (1 microM, 10 microM) and KCl (30 mM, 45 mM, 60 mM), calcium-induced relaxation was gradually decreased. 5. A low concentration of calcium ionophore A-23187 (0.1 microM) did not change calcium-induced relaxation, but A-23187 at a high concentration (1 microM) depressed this relaxation. 6. These results suggest that Na-K-ATPase activation could be responsible for high calcium-induced relaxation.
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PMID:Possible mechanism of high calcium-induced relaxation of rabbit thoracic aorta. 951 85

Ca2+ loss from the sarcoplasmic reticulum (SR) of rabbit inferior vena cava smooth muscle was monitored by measuring the decay of caffeine-induced fura-2 fluorescence transients. Removal of Ca2+ from the extracellular space caused a rapid loss of SR Ca2+ and a decline of cytoplasmic Ca2+ concentration ([Ca2+]i). Simultaneous removal of extracellular Na+ greatly inhibited the rate of this (SR) Ca2+ loss. A rapid loss of SR Ca2+ was induced by 20 microns CPA, regardless of the presence or absence of extracellular Na+ or Ca2+. These effects were not influenced by alterations in membrane potential owing to activity of Ca2(+)-activated K+ channels since 3 mM TEA had no effect on the rate of Ca2+ loss from the SR. These results indicate that when Ca2+ is removed from the extracellular space, it induces Ca2+ release from the SR towards the plasma membrane Na(+)-Ca2+ exchanger which subsequently translocates it from the junctional cytoplasmic space to the extracellular space. When the Na(+)-Ca2+ exchanger is arrested by removal of extracellular Na+ and Ca2+, Ca2+ released from the SR is re-sequestered by the sarco-endo-plasmic reticulum Ca2(+)-ATPase (SERCA). However, when both the Na(+)-Ca2+ exchanger, and, the SERCA are blocked, Ca2+ released from the SR is extruded from the cells by the plasma membrane Ca2(+)-ATPase. These results reveal a hierarchy of interaction between the different Ca2+ transporters in the SR, and cell membranes.
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PMID:Functional linkage of Na(+)-Ca2+ exchange and sarcoplasmic reticulum Ca2+ release mediates Ca2+ cycling in vascular smooth muscle. 988 81


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