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)

Adult male rats were maintained on a nutritionally adequate liquid-diet or laboratory chow and water (control), for 9 days. They were then killed and the parotid glands removed. Enzymatically dispersed acinar-cell preparations were used to study rates of oxygen consumption (QO2) using a Clark oxygen electrode. For both CON and LD cell preparations the basal QO2 was 0.132 (+/- 0.03-0.05) nmol O2 per microgram DNA per min and in each case this was increased approx. 2.4-fold under stimulation by carbachol (10 microM) and approx. 3.1-fold by adrenaline (10 microM). Isoprenaline (10 microM) elicited no significant increase in QO2. Addition of ouabain (2.5 mM) or removal of Ca2+ from the extracellular medium prevented the action of carbachol to increase QO2 over a sustained period. There were no significant differences in the basal, agonist-stimulated, or ouabain-sensitive QO2 by dispersed acinar cells from liquid-diet rats compared to control. The results are consistent with the notion that liquid diet-induced atrophy represents a physiological adaptation rather than a pathological change. Nevertheless, they also indicate that in the acinar cells from liquid-diet rats the Na+/K+ ATPase is required to operate at normal levels of energy consumption despite the reduced acinar-cell volume and consequently lower levels of agonist-elicited transepithelial ion movements known to occur in these cells.
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PMID:Rate of oxygen consumption by parotid atrophic acinar cells from rats fed liquid diet. 748 67

Effects of various receptor agonists on cytoplasmic Ca2+ concentration ([Ca2+]i) were examined in fura-2-loaded Mardin-Darby canine kidney (MDCK) monolayer cells. Carbachol (100 microM) increased [Ca2+]i which slightly declined to a sustained increase in [Ca2+]i. On the other hand, [Ca2+]i elevated by 100 nM bradykinin (BK) declined to a resting level of [Ca2+]i even in the presence of BK. After washout of BK, the subsequent addition of a higher concentration of BK (1 microM) caused a smaller increase in [Ca2+]i than that induced by 100 nM BK. Isoproterenol (100 microM) did not increase [Ca2+]i by itself but caused an transient increase in [Ca2+]i in the presence of 1 mM isobutyl-methylxanthine (IBMX). Prostaglandin E1 (1 microM) resulted in a slight increase in [Ca2+]i which was potentiatedin the presence of 1 mM IBMX. The microsomal Ca(2+)-ATPase inhibitor thapsigargin (100 nM) caused a sustained increase in [Ca2+]i. These results suggest that MDCK cells have multiple Ca2+ signaling pathways which may regulate epithelial cell functions.
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PMID:Multiple calcium signaling pathways in Mardin-Darby canine kidney cells. 753 28

The activity of the Na+/H+ exchanger was studied by measuring the effects of intracellular pH (pHi) and extracellular Na+ [(Na+)o] on pHi recovery and 22Na uptake in rat adipocytes. The resting pHi was acidified from 7.30 +/- 0.02 to 6.99 +/- 0.01 with nigericin in the absence of (Na+)o. pHi recovery induced by 30 mM NaCl was blocked by 100 microM amiloride. The reversibility of the exchanger was studied by Na+ loading, which raised the pHi from 7.30 +/- 0.02 to 7.50 +/- 0.01, and by removing (Na+)o, which decreased pHi to 6.97 +/- 0.01. Both functions of the exchanger, forward and backward, were inhibited by amiloride. The Na+/H+ exchanger was inactive at pHi higher than 7.1 and became increasingly active as pHi decreased to 6.2 (22Na+ uptake, 0.029 +/- 0.003 vs. 0.155 +/- 0.009 nmol/10(5) cells.2.5 min; P < 0.001); this 5-fold stimulation was largely abolished by amiloride (0.025 +/- 0.002; P < 0.001). Na+ influx was also increased as a function of (Na+)o, with an apparent Km of 35 mM. Respective 5- and 44-fold stimulations at 5 mM (0.135 +/- 0.007) and 140 mM (Na+)o (1.228 +/- 0.046 nmol/10(5) cells.2.5 min; P < 0.001) were inhibited by ethylisopropylamiloride. Isoproterenol (Iso; 100 nM) and agents that stimulate cAMP production, such as forskolin (10 microM) and theophyline (1 mM), inhibited the activity of amiloride-sensitive 22Na+ uptake by 85%. Iso inhibited the Na+/H+ exchanger, without affecting the Na+/K(+)-adenosine triphosphatase-dependent and the Na+/K+/Cl- cotransport mechanisms. (Bu)2cAMP (1 mM), a membrane-permeant cAMP analog, mimicked the effects of Iso on the exchanger. The inhibitory effect of Iso was blocked by propranolol, but not by metoprolol, a beta 1-antagonist. In addition, the alpha-adrenergic agonists, phenylephrine (alpha 1) and clonidine (alpha 2), and the alpha-antagonists, prazocin (alpha 1) and yohimbine (alpha 2), did not prevent Iso-induced inhibition of the exchanger. In conclusion, rat adipocytes possess a reversible Na+/H+ exchange mechanism, which is activated by low pHi and normal (Na+)o and is inhibited by Iso via a beta 2-adrenergic receptor stimulation and a cAMP-dependent mechanism.
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PMID:Activation of the Na+/H+ exchanger by cellular pH and extracellular Na+ in rat adipocytes; inhibition by isoproterenol. 778 40

To determine the role of various Na+ transport systems in the edema fluid accumulation after ischemia and reperfusion in the lung, we evaluated the effect of amiloride (a Na+ channel blocker), ouabain (a Na(+)-K(+)-adenosinetriphosphatase blocker), and phloridzin (a Na(+)-glucose cotransport blocker) in isolated rat lungs. Ischemia and reperfusion (I/R) significantly increased the edema accumulation, with the wet-to-dry weight ratios increasing to 10.14 +/- 0.58 from 6.03 +/- 0.05 in control lungs (P < 0.04). Amiloride significantly augmented the amount of edema fluid (wet-to-dry weight ratio 12.26 +/- 0.77), and ouabain further increased the amount of edema (wet-to-dry weight ratio 18.58 +/- 1.00). Phloridzin did not significantly affect edema formation associated with I/R. Isoproterenol decreased the amount of edema formation in the presence and absence of amiloride. This occurred because the endothelial permeability as assessed by filtration coefficient was restored to normal values and less edema formed. The present study indicates that Na+ channels and Na(+)-K(+)-adenosinetriphosphatase, components of the active Na+ absorption transport system, are very important in opposing edema fluid accumulation in rat lungs subjected to I/R injury and operate as an edema safety factor. However, if the endothelial damage associated with I/R is allowed to persist, then the transport processes, even if operative, are insufficient to prevent continuous edema accumulation.
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PMID:Vascular permeability and epithelial transport effects on lung edema formation in ischemia and reperfusion. 783 12

To assess the effect of targeted myocardial beta-adrenergic receptor (AR) stimulation on relaxation and phospholamban regulation, we studied the physiological and biochemical alterations associated with overexpression of the human beta2-AR gene in transgenic mice. These mice have an approximately 200-fold increase in beta-AR density and a 2-fold increase in basal adenylyl cyclase activity relative to negative littermate controls. Mice were catheterized with a high fidelity micromanometer and hemodynamic recordings were obtained in vivo. Overexpression of the beta2-AR altered parameters of relaxation. At baseline, LV dP/dt(min) and the time constant of LV pressure isovolumic decay (Tau) in the transgenic mice were significantly shorter compared with controls, indicating markedly enhanced myocardial relaxation. Isoproterenol stimulation resulted in shortening of relaxation velocity in control mice but not in the transgenic mice, indicating maximal relaxation in these animals. Immunoblotting analysis revealed a selective decrease in the amount of phospholamban protein, without a significant change in the content for either sarcoplasmic reticulum Ca2+ ATPase or calsequestrin, in the transgenic hearts compared with controls. This study indicates that myocardial relaxation is both markedly enhanced and maximal in these mice and that conditions associated with chronic beta-AR stimulation can result in a selective reduction of phospholamban protein.
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PMID:Enhanced myocardial relaxation in vivo in transgenic mice overexpressing the beta2-adrenergic receptor is associated with reduced phospholamban protein. 860 26

1. The role of beta(3)-adrenoceptors in isoprenaline-induced relaxation of carbachol-precontracted ring segments of the rat lower oesophageal sphincter (LOS) was examined. 2. Isoprenaline (10(-8)M-10(-5)M) relaxed ring segments of the LOS in a concentration-dependent manner. Propranolol (10(-7)M) had very little antagonist effect on isoprenaline-induced relaxation. 3. Dobutamine (10(-7)M-10(-4)M), salbutamol (10(-7)-10(-4)M) and BRL 37344 (10(-8)-10(-5)M) also relaxed carbachol-contracted ring segments of the LOS in a concentration-dependent manner. The relaxant responses to these agonists were similarly not antagonized by propranolol (10(-7)M). 4. Cyanopindolol (10(-6)M), produced a parallel rightward displacement of isoprenaline, dobutamine, salbutamol and BRL 37344 concentration-response curves with similar potencies. The pKB values range from 7.3 +/- 0.1 to 7.7 +/- 0.2. 5. The relaxant effect of isoprenaline in the rat LOS was not inhibited by NG-nitro-L-arginine (L-NOARG; 3 x 10(-5)M), glibenclamide (10(-5)M) or tetraethylammonium (1 mM). 6. It was concluded that beta(3)-adrenoceptors mediate isoprenaline-induced relaxation in rat lower oesophageal sphincter and that activation of these receptors was not linked to either ATPase-, Ca(2+)-dependent K+ channels or to NO release.
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PMID:Beta(3)-adrenoceptors mediate smooth muscle relaxation in the rat lower oesophageal sphincter. 927 77

1. The effect of beta-adrenergic stimulation on the relationship between the intracellular Ca2+ transient and the amplitude of the L-type Ca2+ current (ICa) has been investigated in ventricular myocytes isolated from rat hearts. Intracellular [Ca2+] was monitored using fura-2 during field stimulation and while membrane potential was controlled using voltage clamp techniques. 2. The increase in the amplitude, and the rate of decline, of the Ca2+ transient produced by isoprenaline (1.0 mumol l-1) was not significantly different in myocytes generating action potentials and in those voltage clamped with pulses of constant duration and amplitude. 3. Under control conditions, the current-voltage (I-V) relationship for ICa was bell shaped. The amplitude of the Ca2+ transient also showed a bell-shaped voltage dependence. In the presence of isoprenaline, the amplitude of both ICa and the Ca2+ transient was greater at all test potentials and the I-V relationship maintained its bell-shaped voltage dependence. However, the size of the Ca2+ transient was no longer graded with changes in the amplitude of ICa: a small ICa could now elicit a maximal Ca2+ transient. 4. Rapid application of caffeine (10 mmol l-1) was used to elicit Ca2+ release from the sarcoplasmic reticulum (SR). Isoprenaline increased the integral of the subsequent rise in cytoplasmic [Ca2+] to 175 +/- 13% of control. 5. Abbreviation of conditioning pulse duration in the presence of isoprenaline was used to reduce the amplitude of the Ca2+ transient to control levels. Under these conditions, the amplitude of the Ca2+ transient was again graded with the amplitude of ICa in the same way as under control conditions. 6. Nifedipine (2 mumol l-1) was also used to decrease Ca2+ transient amplitude in the presence of isoprenaline. In the presence of isoprenaline and nifedipine, the amplitude of the Ca2+ transient again showed a bell-shaped voltage dependence. 7. The SR Ca(2+)-ATPase inhibitor thapsigargin (2.5 mumol l-1) reduced the effect of isoprenaline on the amplitude of the Ca2+ transient. In the presence of thapsigargin, the size of the Ca2+ transient increased as ICa increased in response to isoprenaline. 8. These data suggest that the increase in the amplitude of the Ca2+ transient produced by beta-adrenergic stimulation in cardiac muscle is due to an increase in the gain of the SR Ca2+ release process, due principally to an increase in the Ca2+ content of the SR.
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PMID:Sarcoplasmic reticulum Ca2+ content, L-type Ca2+ current and the Ca2+ transient in rat myocytes during beta-adrenergic stimulation. 942 81

We studied the influence of prolonged administration of the beta adrenoceptor agonist isoproterenol on contractile parameters and expression of sarcoplasmic reticulum (SR) Ca(++)-ATPase and phospholamban, genes important for Ca++ uptake into the SR. Isoproterenol (Iso), 0.9% NaCl (Ctr), propranolol (Prop) or Iso plus Prop were administered to rats by subcutaneous infusion with osmotic minipumps for 1, 2, 3, 4, 8, 13 and 26 days, respectively. The positive inotropic effect of Iso was impaired in rats pretreated with Iso in vivo. Iso pretreatment shortened time to peak tension (TPT) by 28%, time of relaxation (RT) by 27% and total contraction time (TCT) by 27% compared with the appropriate controls (day 2). The shortening of time-dependent contractile indices started after 1 day of Iso pretreatment, reached a maximum after 2 days and remained reduced for 4 days. Longer treatment by Iso failed to affect time parameters, whereas the positive inotropic effect of Iso added to the isolated muscles persisted. The shortened contractile time parameters were accompanied by diminished mRNA and protein expression of phospholamban (PLB) and SR-Ca(++)-ATPase (SERCA). The mRNA levels for PLB and SERCA were maximally reduced by 31 +/- 1.3% and 41 +/- 1.4% in the Isopretreated group (2 days) respectively. The reduced mRNA levels were accompanied by reduced levels of the corresponding proteins. It is concluded that altered levels of PLB and SERCA probably account for the noted changes in contractile time parameters in the mammalian heart.
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PMID:Long-term beta adrenoceptor-mediated alteration in contractility and expression of phospholamban and sarcoplasmic reticulum Ca(++)-ATPase in mammalian ventricle. 965 99

A cellular suspension from rat submandibular glands was exposed to different concentrations of NH4Cl, and the variations of the intracellular concentration of calcium ([Ca2+]i) and the intracellular pH (pHi) were measured using fura-2 and 2',7'-bis-(2-carboxy-ethyl)-5(6)-carboxyfluorescein. More than 5 mmol/l NH4Cl significantly increased the [Ca2+]i without affecting the response to 100 micromol/l carbachol. When exposed to 1 and 5 mmol/l NH4Cl, the cells acidified immediately. At 30 mmol/l, NH4Cl first alkalinized the cells and the pHi subsequently dropped. This drop reflects the uptake of NH4+ ions that dissociate to NH3 and H+ in the cytosol. These protons are exchanged for extracellular sodium by the Na+/H+ exchanger because the presence of an inhibitor of the exchanger in the medium increased the acidification induced by 1 mmol/l NH4Cl. Ouabain partly blocked the uptake of NH4+. In the combined presence of ouabain and bumetanide (an inhibitor of the Na+-K+-2Cl- cotransporter), 1 mmol/l NH4Cl alkalinized the cells. The contribution of the Na/K ATPase and the Na+-K+-2Cl- cotransporter in the uptake of NH4+ was independent of the presence of calcium in the medium. Isoproterenol increased the uptake of NH4+ by the cotransporter. Conversely, 1 mmol/l extracellular ATP blocked the basal uptake of NH4+ by the cotransporter. This inhibition was reversed by extracellular magnesium or Coomassie Blue. It was mimicked by benzoyl-ATP but not by CTP, GTP, UTP, ADP, or ADPbetaS. ATP only slightly inhibited the increase of cyclic AMP (-22%) by isoproterenol but fully blocked the stimulation of the cotransporter by the beta-adrenergic agonist. ATP increased the release of 3H-arachidonic acid from prelabeled cells but SK&F 96365, an imidazole-based cytochrome P450 inhibitor, did not affect the inhibition by ATP. It is concluded that the activation of a purinoceptor inhibits the basal and the cyclic AMP-stimulated activity of the Na+-K+-2Cl- cotransporter.
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PMID:Regulation of the Na+-K+(NH4+)-2Cl- cotransporter of rat submandibular glands. 1043 Jan 82

We examined the relationship between age-associated lusitropic impairment, heart rate, and Ca(2+)-handling proteins and assessed the efficacy of increasing left ventricular (LV) relaxation via beta-adrenergic stimulation in adult and aging mouse hearts. LV function was measured in isolated, isovolumic blood-perfused hearts from adult (5 mo), old (24 mo), and senescent (34 mo) mice. Hearts were paced from 5 to 10 Hz, returned to 7 Hz, exposed to 10(-6) M isoproterenol, and paced again from 7 to 10 Hz. Age-related alterations in Na(+)/Ca(2+) exchanger (NCX), sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), and phospholamban (PLB) levels were assessed by immunoblot. Despite preserved contractile performance, aging caused impaired lusitropy. Increased pacing caused an elevation in end-diastolic pressure that progressively worsened with age. The time constant of isovolumic pressure decay (tau) was significantly prolonged in old and senescent hearts compared with adults. Relative to adult hearts, the SERCA2a-to-PLB ratios were reduced 68 and 69%, and NCX were reduced 37 and 58% in old and senescent hearts, respectively. Isoproterenol completely reversed the age-associated lusitropic impairments. These data suggest that impaired lusitropy in aging mouse hearts is related to a decreased rate of cytosolic Ca(2+) removal and that accelerating SR Ca(2+) resequestration via beta-adrenergic stimulation can reverse this impairment.
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PMID:Impaired lusitropy-frequency in the aging mouse: role of Ca(2+)-handling proteins and effects of isoproterenol. 1056 64


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