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)

In the myocardium the inhibitory guanine nucleotide-binding regulatory proteins (Gi proteins) mediate negative chronotropic and negative inotropic effects by activation of K+ channels and inhibition of adenylyl cyclase. The concept of a uniform inhibitory action of Gi proteins on myocardial cellular activity has been questioned by the recent observations of adenosine-induced activation of the Na+/Ca(2+) exchange and a carbachol-induced inhibition of the Na+/K(+)-ATPase activity in cardiac sarcolemmal membranes. The aim of the present study, therefore, was to reinvestigate the putative regulation of Na+/Ca(2+) exchange and Na+/K(+)-ATPase activity in purified canine sarcolemmal membranes. These membranes were enriched in adenosine A1 (Maximum number of receptors, Bmax 0.033 pmol/mg) and muscarinic M2 (Bmax 2.9 pmol/mg) receptors and contained Gi2 and Gi3, two Gi protein isoforms, and G0, another pertussis toxin-sensitive G protein, as detected with specific antibodies. The adenosine A1-selective agonist, (-)-N6-(2-phenylisopropyl)-adenosine, and the muscarinic agonist, carbachol, both inhibited isoprenaline-stimulated adenylyl cyclase activity by 25% and 35% respectively, and the stable GTP analogue 5'-guanylylimidodiphosphate inhibited forskolin-stimulated adenylyl cyclase activity by 35% in these membranes. The characteristics of Na+/Ca(2+) exchange and Na+/K(+)-ATPase activity as well as those of the ouabain-sensitive, K(+)-activated 4-nitrophenylphosphatase, an ATP-independent, partial reaction of the Na+/K(+)-ATPase, were in agreement with published data with regard to specific activity, time course of activity and substrate dependency. However, none of these activities were influenced by adenosine, (-)-N6-(2-phenylisopropyl)-adenosine, carbachol, or stable GTP analogs, suggesting that Na+/Ca(2+) exchange and Na+/K(+)-ATPase are not regulated by Gi proteins in canine cardiac sarcolemmal membranes.
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PMID:Evidence against a regulation of Na+/K(+)-ATPase by Gi proteins. Failure to detect an influence of G proteins on Na+/Ca(2+)-exchange in cardiac sarcolemmal membranes. 874 Jan 43

We investigated the effect of dopamine on Na+,K(+)-ATPase activity in cultured aortic smooth muscle cells. Na+,K(+)- ATPase activity was measured by a coupled enzyme assay. Our results demonstrate that dopamine and dopamine receptor agonists, SKF-38393 (a D1 receptor agonist) and quinpirole (a D2 receptor agonist) produced 62%, 50% and 49% inhibition of Na+,K(+)-ATPase activity in aortic smooth muscle cells, respectively. The combination of the two agonists produced inhibition similar to that of dopamine. Dopamine- and the agonist-induced Na+,K(+)-ATPase inhibition was blocked by selective receptor antagonists. The Na+,K(+)-ATPase inhibition by SKF-38393 but not by quinpirole was abolished by pertussis toxin. Na+,K(+)-ATPase inhibition was also achieved by guanosine triphosphate analog GTP-gamma-S. SKF-38393 but not quinpirole stimulated phosphoinositide hydrolysis rate in rat aortic slices. SKF-38393-induced phosphoinositide hydrolysis stimulation was reversed by SCH-23390, a dopamine D1 receptor antagonist, and attenuated by pertussis toxin. In conclusion, our observations indicate that dopamine and dopamine receptor agonists inhibit Na+,K(+)-ATPase activity through specific vascular receptors. Dopamine D1 receptors are linked to pertussis toxin sensitive-mechanism(s) and a GTP-binding protein appears to be coupled to the enzyme inhibition. Finally, the inhibition of Na+,K(+)-ATPase activity in response to dopamine D1 receptor activation may be mediated by the phospholipase C signaling pathway.
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PMID:Regulation of Na+,K(+)-ATPase activity by dopamine in cultured rat aortic smooth muscle cells. 881 57

In human airway epithelial cell lines 9HTEo- and CFNPE9o, histamine causes a transient elevation of intracellular free calcium concentration ([Ca2+]i) detected by fura 2 fluorescence, which is due to both release from intracellular stores and extracellular Ca2+ entry. The effect of histamine is abolished by the Ca(2+)-ATPase inhibitor thapsigargin. Histamine also stimulates inositol phosphate accumulation. Changes in [Ca2+]i and inositol phosphate production exhibit a similar dose-response relationship for histamine (maximal effect at 10(-4) M), with both phenomena being blocked by the H1 antagonist mepyramine and being insensitive to pertussis toxin treatment. The effects of histamine on phosphoinositide metabolism and [Ca2+]i are abolished by a short-term preincubation with phorbol ester, and this effect is reversed by staurosporine and calphostin C, suggesting a feedback regulation by protein kinase C. The results indicate that human airway epithelial cells contain H1 receptors coupled to phospholipase C through a pertussis toxin-insensitive G protein.
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PMID:Histamine activates phospholipase C in human airway epithelial cells via a phorbol ester-sensitive pathway. 889 15

Low concentrations of angiotensin II (Ang II) increase, whereas high concentrations inhibit the apical Na/H antiporter activity in the proximal tubule, but the respective roles of the different signaling pathways in mediating these effects remains unsettled. We studied the effects of both low and high doses of Ang II in the presence of selective signaling pathway inhibitors, on the apical Na/H antiport activity of rat proximal tubule. Experiments were carried out in intact cells of freshly prepared tubule fragments obtained from the outer third of cortex, that is, devoid of basolateral Na/H antiport activity in the absence of bicarbonate transport and H(+)-ATPase activity. In tubules acid-loaded by an NH4Cl prepulse, Na/H antiport activity was assessed by the initial rate of intracellular pH recovery (dpHi/dt), measured with BCECF. When tubules were preincubated with low dose Ang II (10(-11) M for 3 min), dpHi/dt increased by 25 +/- 8%, whereas incubation with high dose Ang II (10(-7) M for 3 min) decreased dpHi/dt by 30 +/- 4%, compared to control (P < 0.01 in both cases). Both effects were abolished in the presence of 2.10(-3) M amiloride. Low dose Ang II-induced increase in dpHi/dt was not affected by preincubation with a specific PKA inhibitor, Rp-CPT-cAMP 10(-4) M, and was completely abolished by preincubation with PKC inhibitors, staurosporine 10(-7) M, sphingosine 5.10(-6) M, or calphostin 10(-6) M. In addition, pretreatment of rats with pertussis toxin led to a partial inhibition of the effect of low dose Ang II. The high dose-Ang II-induced decrease in dpHi/dt was not affected by pretreatment with a calcium-calmodulin kinase inhibitor W-7 10(-4) M. Conversely, pretreatment with the cytochrome P-450 inhibitor econazole 10(-5) M reversed the inhibitory effect of high dose Ang II to a stimulatory effect (24 +/- 8%, P < 0.01), quantitatively similar to the effect of low dose Ang II. In addition, arachidonate was found to exert an econazole-sensitive dose-dependent inhibitory effect on dpHi/dt, and 5,6-EET 10(-6) M, a cytochrome P-450 derived-arachidonic acid metabolite, induced a 38 +/- 9% inhibition, similar to that observed with high dose Ang II alone. There was no additive effect of 5,6-EET and high dose Ang II. Finally, pretreatment with two PLA2 inhibitors (BromoPhenacylBromide, 6.10(-6) M, and oleyloxyethyl phosphorylcholine, 5.10(-6) M) reversed the inhibitory effect of high dose Ang II to a stimulatory effect (32 +/- 11% and 25 +/- 11%, respectively, P < 0.05 for both inhibitors). We conclude that, in intact rat proximal cells, low dose Ang II stimulates the apical Na/H antiport through a pertussis toxin-sensitive G protein-dependent PKC pathway, whereas high dose Ang II inhibits the Na/H antiport activity through the PLA2- and cytochrome P-450-dependent metabolites of arachidonate.
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PMID:Signaling pathways in the biphasic effect of angiotensin II on apical Na/H antiport activity in proximal tubule. 891 15

In mouse NIH 3T3 cells, the mitogens bombesin and thrombin induced Ca2+ release from intracellular stores. Ca2+ release induced by bombesin was inhibited by the Ca(2+)-ATPase inhibitor thapsigargin, while Ca2+ release induced by thrombin was unaffected by this agent. The Ca(2+)-release response to bombesin was not affected by pertussis toxin, but the response to thrombin was abolished by the toxin. Stable transfectants overexpressing the G-protein subunit type alpha 9 showed an accentuated response to bombesin, indicating that the bombesin receptor was coupled to a Gq-like G-protein. Together, these results show that the two mitogenic receptors are coupled to distinct G-proteins that affect functionally different pools of Ca2+. Organization of signalling pathways in this manner may allow cells to differentially encode information from different signals.
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PMID:Bombesin and thrombin affect discrete pools of intracellular calcium through different G-proteins. 894 71

Acetylcholine and adenosine triphosphate (ATP) raise intracellular Ca2+ concentration via muscarinic receptors and P2U purinoceptors by releasing Ca2+ from intracellular Ca2+ stores in the neural retina of early embryonic chick. The signal transduction mechanisms for the muscarinic and purinergic Ca2+ responses were studied with fura-2 fluorescence measurements. Li+ (1 mM), which inhibits phosphatidylinositol metabolism, enhanced both the Ca2+ rises to carbamylcholine (CCh. 30 microM) a muscarinic agonist and ATP (200 microM). Thapsigargin (250 nM), an inhibitor of Ca(2+)-ATPase of inositol trisphosphate (IP3)-sensitive Ca2+ stores, abolished both the Ca2+ rises to CCh (100 microM) and ATP (500 microM). U-73122 (2 microM), an inhibitor of phospholipase C beta, suppressed the Ca2+ rise to ATP (500 microM), but its analog U-73343 (2 microM) did not suppress it. In contrast, both U-73122 and U-73343 suppressed the Ca2+ the Ca2+ rise to CCh (100 microM). Pertussis toxin (250 ng/ml) suppressed the ATP-induced Ca2+ rise at least partly, whereas no inhibition was observed on the CCh-induced Ca2+ rise. Cross-talk occurred between the muscarinic and purinergic Ca2+ mobilizations but they were not occlusive. This study suggests that the muscarinic and purinergic Ca2+ mobilizations utilize IP3-sensitive Ca2+, stores, but different signal transduction pathways are involved in between the muscarinic and purinergic Ca2+ responses.
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PMID:Muscarinic and purinergic Ca2+ mobilizations in the neural retina of early embryonic chick. 896 Sep 76

Autotaxin (ATX) is an extracellular enzyme and an autocrine motility factor that stimulates pertussis toxin-sensitive chemotaxis in human melanoma cells at picomolar to nanomolar concentrations. This 125-kDa glycoprotein contains a peptide sequence identified as the catalytic site in type I alkaline phosphodiesterases (PDEs), and it possesses 5'-nucleotide PDE (EC 3.1.4.1) activity (Stracke, M. L., Krutzsch, H. C., Unsworth, E. J., Arestad, A., Cioce, V., Schiffmann, E., and Liotta, L. (1992) J. Biol. Chem. 267, 2524-2529; Murata, J., Lee, H. Y., Clair, T., Krutsch, H. C., Arestad, A. A., Sobel, M. E., Liotta, L. A., and Stracke, M. L. (1994) J. Biol. Chem. 269, 30479-30484). ATX binds ATP and is phosphorylated only on threonine. Thr210 at the PDE active site of ATX is required for phosphorylation, 5'-nucleotide PDE, and motility-stimulating activities (Lee, H. Y., Clair, T., Mulvaney, P. T., Woodhouse, E. C., Aznavoorian, S., Liotta, L. A., and Stracke, M. L. (1996) J. Biol. Chem. 271, 24408-24412). In this article we report that the phosphorylation of ATX is a transient event, being stable at 0 degrees C but unstable at 37 degrees C, and that ATX has adenosine-5'-triphosphatase (ATPase; EC 3.6.1.3) and ATP pyrophosphatase (EC 3.6.1.8) activities. Thus ATX catalyzes the hydrolysis of the phosphodiester bond on either side of the beta-phosphate of ATP. ATX also catalyzes the hydrolysis of GTP to GDP and GMP, of either AMP or PPi to Pi, and the hydrolysis of NAD to AMP, and each of these substrates can serve as a phosphate donor in the phosphorylation of ATX. ATX possesses no detectable protein kinase activity toward histone, myelin basic protein, or casein. These results lead to the proposal that ATX is capable of at least two alternative reaction mechanisms, threonine (T-type) ATPase and 5'-nucleotide PDE/ATP pyrophosphatase, with a common site (Thr210) for the formation of covalently bound reaction intermediates threonine phosphate and threonine adenylate, respectively.
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PMID:Autotaxin is an exoenzyme possessing 5'-nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities. 899 94

Bacterial lipopolysaccharide (LPS)-induced exocytosis is one of the primary immune responses of the Limulus granulocyte (GR). Exocytosis can be mediated by guanine nucleotide-binding protein (G-protein)-linked surface receptors that activate phospholipase C (PLC) to produce inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes intracellular Ca2+ ([Ca2+]i), which can lead to exocytosis. We used activators and inhibitors of known signal transduction pathways to investigate the signaling pathway responsible for LPS-induced exocytosis in the GR. These compounds have been shown to similarly effect pathways in vertebrate and invertebrate systems and this assumption is made here. Pretreatment of GRs with cholera and pertussis toxins, which modulate G-proteins, and U73122, which inhibits PLC, inhibited LPS-induced exocytosis, but pretreatment with the tyrosine kinase inhibitor herbimycin did not. In contrast, exocytosis was induced with fluoride (a G-protein activator) and thapsigargin with Mg2+ (an inhibitor of endomembranous Ca(2+)-ATPase). Exocytosis was not induced by phorbol ester, which mimics DAG to activate protein kinase C (PKC) and it was not effected by ethanol or chelerythrine, which inhibit phospholipase D and PKC, respectively. Microinjection of GRs with different concentrations of IP3, an IP3 analog (DL-2,3,6,trideoxy-myo-inositol 1,4,5-triphosphate), Mg2+, or Ca2+ induced different percentages of exocytosis in individual cells, while HEPES buffer did not. Microfluorometric analysis of intracellular Mg2+ ([Mg2+]i) and [Ca2+]i, using the dyes Mag Fura-2AM and Calcium Green 5N, respectively, revealed [Mg2+]i and [Ca2+]i fluxes during LPS-induced exocytosis. This study suggests that LPS induces exocytosis in the Limulus GR through activation of G-protein-coupled receptors, which stimulate the IP3 signaling pathway to induce both [Ca2+]i and [Mg2+]i fluxes to facilitate vesicular and plasma membrane fusion. This is the first demonstration of the signal transduction pathway responsible for the primary immune response of the GR.
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PMID:Signal transduction during exocytosis in Limulus polyphemus granulocytes. 901 85

The present study was undertaken to examine the effect of dopamine D2 receptor activation on Na+,K(+)-ATPase activity in rat renal proximal tubule suspension. Bromocriptine, a dopamine D2 receptor agonist, produced a concentration (10(-9)-10(-5) M) dependent stimulation of Na+,K(+)-ATPase activity which was antagonized by pretreating the tubules with domperidone (1 microM), a dopamine D2 receptor antagonist. Forskolin (1 microM), a direct activator of adenylyl cyclase, inhibited Na+ K(+)-ATPase activity and reversed the stimulation of Na+,K(+)-ATPase activity induced by bromocriptine. Pertussis toxin (200 ng/ml) treatment also abolished the bromocriptine-induced stimulation of Na+,K(+)-ATPase activity. Bromocriptine attenuated forskolin-stimulated cAMP accumulation which was blocked by pertussis toxin treatment of the tubules. The data suggest that dopamine D2 receptor activation by bromocriptine leads to stimulation of Na+,K(+)-ATPase activity which may be mediated through a pertussis-sensitive G protein and inhibition of adenylyl cyclase in rat renal proximal tubules.
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PMID:Bromocriptine stimulates Na+, K(+)-ATPase in renal proximal tubules via the cAMP pathway. 906 96

Occupancy of oxytocin receptor (OTR) binding sites in pregnant rat myometrial membranes with iodinated oxytocin antagonist (OTA), followed by detergent solubilization and size selection, showed that radioactivity eluted in two distinct peaks: one corresponding in size to the isolated receptor (approximately 60 kDa) and the other ranging from 240 to 320 kDa. The unliganded 240- to 320-kDa fraction contained OTRs coupled to G proteins, as the addition of oxytocin (OT) increased guanosine 35S-labeled 5'-O-(3-thiotriphosphate) binding up to twofold in a dose-dependent manner. The effects of OT were blocked by coincubation with OTA. G protein alpha-subunits associated with OTRs in the 240- to 320-kDa peak were identified by immunoadsorption. Significant amounts of both G alpha q/11 and G alpha i3 were associated with the OTR; a lesser amount of G alpha s was complexed. Using the same approach but with antibodies to effector enzymes, we observed that phospholipase C beta 1 (PLC beta 1) and PLA2 were also associated with the OTR. The results corroborate the well-established interaction of OTR with Gq and further show that Gi coupling might be an important component of OTR signal transduction. To further investigate the interaction of Gi with the OTR, we showed that OT stimulation of guanosine 5'-triphosphatase activity in intact myometrial membranes was inhibited by pertussis toxin. Pertussis toxin-stimulated ADP ribosylation of G alpha i in myometrial membranes was also decreased by OT treatment. These findings with pertussis toxin strongly indicate that OTR is coupled to Gi in rat myometrial membranes. The 60-kDa OTR peak (noncoupled receptor) was demonstrable in the myometrium only before the end of gestation and after parturition and accounted for about one-half the 125I-OTA binding activity. At term, there was about a fivefold increase in binding and almost a complete shift to the 240- to 320-kDa-size complex. Thus the established increased sensitivity of the myometrium to OT at term could be the result of both upregulation of OTRs and an increase in the fraction of receptors coupled to signal transduction components, one of which is Gi.
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PMID:Coupling of oxytocin receptor to G proteins in rat myometrium during labor: Gi receptor interaction. 917 88


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