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. Azumolene sodium is a new water-soluble derivative of dantrolene sodium that also acts as a skeletal-muscle relaxant. 2. Azumolene (6 mumol/L) inhibited the hypercontractility induced separately by 3% halothane, 2 mmol/L caffeine and 80 mmol/L potassium chloride in isolated malignant hyperpyrexia (MH)-susceptible muscle. Azumolene was equipotent with dantrolene in inhibiting the abnormal responses. 3. Like dantrolene, azumolene (6 mumol/L) not only prevented but reversed the abnormal contractures induced by halothane and caffeine. Contracture responses to caffeine were also modified by azumolene in control preparations. 4. In the presence of maximal effective concentrations of dantrolene, azumolene failed to further relax caffeine-induced contractures, and the converse was also true. This was observed in both MH-susceptible and control preparations. 5. Sarcoplasmic reticulum Ca(2+)-dependent ATPase activity from MH-susceptible and control muscle was not affected by azumolene. 6. Like dantrolene, azumolene may inhibit Ca2+ release directly from the sarcoplasmic reticulum and be of therapeutic value for the treatment of MH.
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PMID:The effect of azumolene on hypercontractility and sarcoplasmic reticulum Ca(2+)-dependent ATPase activity of malignant hyperpyrexia-susceptible porcine skeletal muscle. 183 2

Calcium transport of skeletal muscle sarcoplasmic reticulum was comparatively studied in hibernating and summer active European hamsters (Cricetus cricetus L.). Crude homogenates from psoas, soleus and mixed skeletal muscles were used. Protein yield was strongly reduced in the muscle homogenates of hibernating hamsters. The calcium concentration in the muscle of hibernating hamsters was increased to a much higher content than in the serum. In the same animals the maximal rate of calcium uptake and the calcium storing capacity of sarcoplasmic reticulum were augmented by 43% and respectively 17%. Kinetic experiments with various concentrations of free calcium revealed in the hibernating animals higher uptake rates and a lower apparent calcium affinity than in the summer active hamsters. Some shift of calcium uptake rate and calcium affinity similar to that of a fast-twitch muscle was also observed in winter active animals kept at 22 degrees C under natural photoperiod. By contrast, the activity of the calcium dependent ATPase was not increased, suggesting a tighter coupling during hibernation between calcium dependent ATP-hydrolysis and calcium transport. No seasonal difference was observed in the calcium release by KCl-caffeine from calcium loaded vesicles of sarcoplasmic reticulum. Proportion and size of fibre types were studied with cold cross sections from psoas and soleus muscles. An average atrophy of about 25% was found during hibernation in both muscles. Cytochemistry revealed, however, a different reduction of cross area between type-I- and type-II-fibres, which reaches values up to 46% in the type-II-fast-fibres of the slow soleus muscle. Electron microscopy did not show any definite change in the distribution and amount of sarcoplasmic reticulum. The results suggest that during hibernation a modulation in the properties of calcium transport ATPase of sarcoplasmic reticulum occurs to better support the calcium transport function at low temperatures, which in turn warrants the restoration of ion homeostasis in the course of the arousal.
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PMID:The modulation of the calcium transport by skeletal muscle sarcoplasmic reticulum in the hibernating European hamster. 184 Jan 24

Three, non-cytosolic Ca2+ pools were characterized in intact PC12 cells. The first pool, sensitive to both inositol 1,4,5-trisphosphate and caffeine (Zacchetti, D., Clementi, E., Fasolato, C., Zottini, M., Grohovaz, F., Fumagalli, G., Pozzan, T., and Meldolesi, J. (1991) J. Biol. Chem. 266, 20152-20158) accounts for approximately equal to 200 microM of Ca2+/liter of cell water (less than 30% of total exchangeable Ca2+) and takes up Ca2+ from the cytosol via a Ca(2+)-ATPase, blocked by thapsigargin. A second pool, approximately equal to 400 microM/liter, is insensitive to both inositol 1,4,5-trisphosphate, caffeine, and thapsigargin and is released by the Ca2+ ionophore ionomycin. This pool is probably heterogeneous and its intracellular localization and physiological roles remain undefined. The third pool, approximately equal to 170 mumoles of Ca2+/liter, was discharged by the combination of ionomycin together with a substance that collapsed intracellular pH gradients, such as monensin or NH4Cl. This indicates that the pool is acidic, at variance with the first two. When exocytosis was stimulated, the size of this pool declined, indicating its primary residence within secretory granules. In the conditions of our experiments no major transfer of Ca2+ among the pools seemed to occur. This is the first comprehensive description of non-cytosolic Ca2+ pools investigated in intact neurosecretory cells by non-invasive procedures.
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PMID:Intracellular Ca2+ pools in PC12 cells. Three intracellular pools are distinguished by their turnover and mechanisms of Ca2+ accumulation, storage, and release. 193 77

Previous studies have shown the existence of functionally distinguishable inositol 1,4,5-trisphosphate- (IP3) sensitive and IP3-insensitive nonmitochondrial intracellular Ca2+ pools in acinar cells of the exocrine pancreas. For further characterization of Ca2+ pools, endoplasmic reticulum (ER) membrane vesicles were separated by Percoll gradient centrifugation which allowed us to distinguish five discrete fractions designated P1 to P5 from the top to the bottom of the gradient. Measuring Ca2+ uptake and Ca2+ release with a Ca2+ electrode, we could differentiate three nonmitochondrial intracellular Ca2+ pools: (i) an IP3-sensitive Ca2+ pool (IsCaP), vanadate- and caffeine-insensitive, (ii) a caffeine-sensitive Ca2+ pool (CasCaP), vanadate- and IP3-insensitive, and (iii) a vanadate-sensitive Ca2+ pool (VasCaP), neither IP3- nor caffeine-sensitive, into which Ca2+ uptake is mediated via a Ca2+ ATPase sensitive to vanadate at 10(-4) mol/liter. A fourth Ca2+ pool is neither IP3- nor caffeine- or vanadate-sensitive. Percoll fraction P1 contained essentially the IsCaP, CasCaP and VasCaP and was mainly used for studies on Ca2+ uptake and Ca2+ release. When membrane vesicles were incubated in the presence of caffeine (2 x 10(-2) mol/liter), Ca2+ uptake up to the steady state [Ca2+] did not appear to be altered as compared to the control Ca2+ uptake. However, in control vesicles spontaneous Ca2+ release occurred after the steady state had been reached, whereas caffeine-pretreated vesicles did not spontaneously release Ca2+. Addition of IP3 at steady state [Ca2+] induced similar Ca2+ release followed by Ca2+ reuptake in both caffeine-pretreated and control vesicles. However, when caffeine was acutely added at steady state, Ca2+ was released from all Ca2+ pools including the IsCaP. Following Ca2+ reuptake after IP3 had been added, a second addition of IP3 to control vesicles induced further but smaller Ca2+ release, and a third addition resulted in a steady Ca2+ efflux by which all Ca2+ that had been taken up was released. This steady Ca2+ release started at a Ca2+ concentration between 5.5-8 x 10(-7) mol/liter and could also be induced by the IP3 analogue inositol 1,4,5-trisphosphorothioate (IPS3) or by addition of Ca2+ itself. Ruthenium red (10(-5) mol/liter) inhibited both caffeine-induced as well as Ca2(+)-induced but not IP3-induced Ca2+ release. Heparin (100 micrograms/ml) inhibited IP3- but not caffeine-induced Ca2+ release. The data indicate the presence of at least three separate Ca2+ pools in pancreatic acinar cells: the IsCaP, CasCaP and VasCaP. During Ca2+ uptake these Ca2+ pools appear to be separate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interaction of caffeine-, IP3- and vanadate-sensitive Ca2+ pools in acinar cells of the exocrine pancreas. 200 14

Caffeine sensitivity was studied in chemically skinned muscle fibers from vastus lateralis muscle obtained by biopsy during reconstructive knee surgery from 15 otherwise healthy young individuals. Muscle fiber type was determined by contracture occurring in strontium (slow-oxidative, type I fiber) or calcium (both type I and type II, fast glycolytic fiber) solutions and in several fibers after contracture testing by ATPase enzyme histochemistry. Caffeine sensitivity (mean +/- SD), defined as the threshold concentration inducing more than 10% of the maximal tension obtained with a calcium 3 x 10(-5) mM solution was 2.7 +/- 1.3 mM in 37 type I fibers, whereas it was 6.9 +/- 2.4 mM in 61 type II fibers. A paired t test showed a significantly increased sensitivity to caffeine in type I fibers (P less than 0.001) in 13 individuals in whom the two fiber types were identified. The mean (+/- SD) difference between type I and type II fibers was 4.1 +/- 1.9 mM. Type I fibers contracted with greater tension in response to the increasing concentration of caffeine than did type II fibers (P less than 0.05). These skinned fiber studies showed significantly different caffeine sensitivities between human type I and type II muscle fibers, as previously shown in animal muscles. The findings that human type I muscle fibers have higher caffeine sensitivity than type II muscle fibers should be helpful for the interpretation of the in vitro contracture test done in muscle strips containing type I and type II fibers in varying proportions.
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PMID:Fiber-type specific caffeine sensitivities in normal human skinned muscle fibers. 213 77

The triple ATPase activities of washed spermatozoa of oligoasthenospermic men (but not of normals) were enhanced by the addition of caffeine and theophylline, which are known to have a stimulating effect on sperm motility. The biochemical mechanism of action of caffeine and theophylline on sperm homeostasis is discussed.
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PMID:The effects of caffeine and theophylline on the triple adenosine triphosphatase enzyme activities of spermatozoa from males with oligoasthenospermia. 213 54

We tested the hypothesis that the adenylate cyclase system and Na+, K(+)-ATPase are reciprocally related in rat pancreatic islets. We studied the effect of theophylline, caffeine, and dibutyryl cyclic AMP on Na+, K(+)-ATPase activity in a membrane preparation from collagenase-isolated rat islets. Theophylline, caffeine, or dibutyryl cyclic AMP, in concentrations of 1 mM, all inhibited Na+, K(+)-ATPase activity (44,62, and 43%, respectively). Kinetic analysis indicated that theophylline and dibutyryl cAMP inhibit Na+, K(+)-ATPase by different mechanisms; theophylline decreased Vmax and decreased apparent Km (ATP), whereas dibutyryl cAMP decreased Vmax and increased apparent Km (ATP). Similar inhibition of Na+, K(+)-ATPase by theophylline or dibutyryl cAMP was noted in a particulate fraction from rat kidney and in a purified porcine brain Na+, K(+)-ATPase preparation. The adenylate cyclase system and Na+, K(+)-ATPase may act reciprocally in pancreatic islets and in other tissues. In the beta cell this relationship may be essential in coordinating consumption of ATP in the stimulated, as opposed to the rest, state.
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PMID:Relationships between adenylate cyclase and Na+, K(+)-ATPase in rat pancreatic islets. 215 93

The mechanism of the inhibitory effect of caffeine on smooth muscle contraction was examined using chicken gizzard. Caffeine (0.1-5 mmol/l) inhibited the KCl-induced contraction of the muscle with an IC50 of 1.1 mmol/l. Forskolin (0.01-10 mumol/l) also inhibited KCl-induced contraction. The inhibitory effect of caffeine was potentiated by a low concentration of forskolin (0.3 mumol/l) and the inhibitory effect of forskolin was potentiated by a low concentration of caffeine (0.1 mmol/l). Although caffeine and forskolin increased tissue cyclic AMP levels, caffeine inhibited the KCl-induced contraction more strongly than forskolin at a given cyclic AMP level. Caffeine (1-40 mmol/l) inhibited the contractions induced by 3 mumol/l Ca2+ in Triton X-100-permeabilized muscle. Caffeine (1-40 mmol/l) inhibited the phosphorylation of 20 kDa myosin light chain (MLC) in native actomyosin preparation and the inhibition was enhanced by decreasing the ATP concentration in the reaction medium. Calmodulin (CaM) activity, as monitored by Ca2+/CaM-dependent erythrocyte membrane (Ca2+ + Mg2+)-ATPase, was not affected by 20 mmol/l caffeine. Time-dependent dephosphorylation of MLC upon removal of Ca2+, an indicator of phosphate activity, was not affected by caffeine. Caffeine also inhibited the Ca2(+)-independent contraction in thiophosphorylated permeabilized muscle. These results indicate that caffeine inhibits smooth muscle contraction by a direct inhibition of MLC kinase and actin-myosin interaction. A part of the inhibitory effect may be mediated by cyclic AMP-dependent mechanism(s).
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PMID:Direct inhibition of chicken gizzard smooth muscle contractile apparatus by caffeine. 216 Jun 18

A light hepatic microsomal preparation was fractionated by sucrose-density centrifugation into one rough, one intermediate and two smooth fractions. The four fractions were characterized with respect to parameters relevant to Ca2+ sequestration. Ca2(+)-ATPase activity was similar in the rough, intermediate and smooth I fractions, but lower in the smooth II fraction. Ca2+ accumulation was the highest in the smooth I and intermediate fractions. On the other hand, Ca2+ efflux from the rough fraction was several-fold faster than from the smooth I fraction. All four subfractions exhibited specific binding sites for inositol 1,4,5-trisphosphate (IP3) and ryanodine; however, the receptors were especially enriched in the smooth I fraction. The total binding sites for ryanodine in that fraction exceeded the number of binding sites for IP3 by about 10-fold. The two receptors responded differently to pharmacological agents; caffeine and dantrolene strongly inhibited ryanodine binding but not IP3 binding, whereas heparin inhibited IP3 binding only. Thus the two receptors are distinct entities. The four fractions also showed distinct gel electrophoretic patterns. The use of two different SDS/polyacrylamide-gel gradients and two protein-staining methods revealed major differences in the distribution of the bands corresponding to Mr values of (x 10(-3) 380, 320, 260, 170, 90, 29 and 21. These proteins were enriched in the smooth fraction. The results indicate that the smooth I fraction might have special importance in stimulus-evoked Ca2(+)-release processes.
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PMID:Distinct ryanodine- and inositol 1,4,5-trisphosphate-binding sites in hepatic microsomes. 216 20

Caffeine (0.1-10 mM) produced a biphasic effect on Na(+)-K+ ATPase activity in the rat heart sarcolemmal preparations. The Na(+)-K+ ATPase activity was stimulated by about 25% at low concentrations (0.1-1 mM), whereas the enzyme was inhibited by about 25% at higher concentrations (10 mM) of caffeine. The stimulatory effect of 1 mM caffeine was associated with about 30% increase in the Vmax value for Na(+)-K+ ATPase, whereas the depressant action of 10 mM caffeine was associated with an increase of the Km value from 1.4 to 2.1 mM ATP. The Na(+)-induced Ca++ release from the sarcolemmal vesicles was stimulated with caffeine in a concentration-dependent manner; about 80% increase in the activity was observed at 0.1 mM caffeine. The apparent Ka (millimolar Na+) values for the Na(+)-induced Ca++ release were about 17 and 6 in the absence and presence of 1 mM caffeine, respectively. However, the sarcolemmal Na(+)-dependent Ca++ uptake and ATP-independent Ca++ binding were not affected, whereas the ATP-dependent Ca++ accumulation and Ca+(+)-stimulated ATPase activities were depressed by 1 to 10 mM caffeine. This agent at concentrations of 0.1 to 10 mM produced a biphasic effect on the contractile activity of the isolated perfused rat heart. The initial transient positive inotropic (30-60%) effect was followed by a sustained negative inotropic (50-80%) response of the drug; the delayed decrease in contractile force was associated with a significant increase (35-50%) in the resting tension. The initial positive inotropic effect of caffeine was dependent on the concentration of Ca++ (0.2-3 mM) in the perfusion medium; however, this response was attenuated either by lowering the concentration of Na+ from 140 to 35 mM or by different concentrations (0.5-1 mM) of amiloride in the medium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiac sarcolemma as a possible site of action of caffeine in rat heart. 217 96


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