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

---

Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal operation of the Na+ pump (Na+, K(+)-ATPase) is essential for the maintenance of neurotransmission. Filtration through Sephadex G-50 of a brain soluble fraction allowed the separation of peaks I and II fractions, respectively stimulating and inhibiting synaptosomal membrane Na+, K(+)-ATPase activity. Peaks I and II were isolated from rat cerebral cortex and their effect together with serotonin (5-HT) was studied on ATPase activity by estimating K(+)-p-nitrophenylphosphatase activity in brain cortex synaptosomal membranes. It was observed that 10(-5) or 10(-4) M 5-HT failed to modify either control membrane enzyme activity or peak I activatory effect; on the other hand, such 5-HT concentrations significantly suppressed peak II inhibitory effect. This ability of 5-HT to reverse the inhibitory effect of endogenous factors on Na+, K(+)-ATPase activity could well be a new 5-HT modulatory action within the brain.
...
PMID:Serotonin reverses the inhibitory effect of a brain soluble fraction on synaptosomal membrane Na+, K(+)-ATPase activity. 755 May 73

In the choroid plexus, the ion pump Na+,K(+)-ATPase regulates the production of cerebrospinal fluid. We now report that incubation of choroid plexus with an activator of protein kinase C, phorbol 12,13-dibutyrate, strongly stimulates the phosphorylation of Na+,K(+)-ATPase and inhibits its activity. Similar effects were obtained with serotonin, which in the choroid plexus stimulates phosphoinositide turnover, thereby activating protein kinase C. Serotonin (10 microM) increased by about 10-fold the amount of phosphorylated Na+,K(+)-ATPase and significantly reduced its activity. Two-dimensional peptide mapping showed comigration of Na+,K(+)-ATPase phosphorylated by either phorbol 12,13-dibutyrate or serotonin in intact cells and by protein kinase C in vitro. These results demonstrate that first messengers can regulate the activity of Na+,K(+)-ATPase through a mechanism involving protein phosphorylation. Moreover, they provide a plausible mechanism for the demonstrated ability of serotonin to decrease cerebrospinal fluid production.
...
PMID:Na+,K(+)-ATPase in the choroid plexus. Regulation by serotonin/protein kinase C pathway. 785

1. Endosulfan insecticide is a polychlorinated compound used for controlling a variety of insects; it is practically water-insoluble, but readily adheres to clay particles and persists in soil and water for several years. Its mode of action involves repetitive nerve-discharges positively correlated to increase in temperature. This compound is extremely toxic to most fish and can cause massive mortalities. In fish, it causes marked changes in Na and K concentrations, decrease in blood Ca(2+) and Mg levels and inhibits Na, K and Mg-dependent ATPase (in brain). 2. Bioaccumulation of endosulfan is reported for marine animals; however, freshwater animals (e.g., crayfish) accumulate it to some extent, but they lose the compound rapidly during depuration. Endosulfan is generally less toxic to aquatic invertebrates than fish. However, it causes decreases in adenylate energy charge, oxygen consumption, hemolymph amino acids, succinate dehydrogenase, heart-beat (mussel) and altered osmoregulation. 3. Generally, mammals are less susceptible to endosulfan's toxicity than aquatic animals. The majority of studies conducted on laboratory mammals can be summarized. (a) Neurotoxicity: male rats are more sensitive than females to endosulfan, which decreases brain and plasma acetylcholinesterase activity. Endosulfan I (a metabolite) causes a significant change in norepinephrine, 5-HT and GABA. (b) Renal toxicity: inhibition of MFOs activity was noticed in rats; other effects included changes in proximal convoluted tubules and necrosis of the tubular epithelium. (c) Hepatotoxicity: chemically-induced aminopyrine N-demethylase and aniline hydrolase were found in rat liver, and reduction in the glycogen level occurred. (d) Hematologic toxicity: endosulfan exposure resulted in a significant decrease in the level occurred. (d) Hematologic toxicity: endosulfan exposure resulted in a significant decrease in the erythrocyte glutathione reductase, hemoglobin amount, RBC number and mean corpuscular volume. 4. Respiratory toxicity: involved dyspnea, acute emphysema, cyanosis and hemorrhages in teh interalveolar portions of rat's lungs. 5. Biochemical: in rats, endosulfan caused increased glucose-6-phosphate dehydrogenase activity, blood glucose level, phospholipid contents of the microsomal and surfactant system, and profoundly induced the activity of alcohol dehydrogenase and cytosolic glutathione S-transferases. It also decreased significantly Na+, K+ and Mg(2+) ATPases, plasma calcium level and alkaline phosphatase in the intestinal epithelium. 6. Immunologic toxicity: rat serum antibody titer to tetanus toxin, IgG, IgM and gammaglobulins were significantly reduced. 7. Reproductive toxicity: degenerative changes in the seminiferous epithelium, induction of the rate-limiting enzyme in testosterone production (3beta-hydroxysteroid transferase and 17 beta-hydroxysteroid transferase), histological changes in reproductive organs, testicular atrophy and the occurrence of ovarian cysts were noticed in rat. Reduction in the weight of secondary sex organ was also observed.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Bioaccumulative potential and toxicity of endosulfan insecticide to non-target animals. 790 Sep 59

1. Small strips from third-order branches of rabbit mesenteric artery (approximately 150-200 microM wide) contracted in response to noradrenaline (10 microM) or 5-hydroxytryptamine (5-HT; 10 microM) in oxygenated Krebs solution containing 2.5 mM Ca2+. In a Ca(2+)-free mock intracellular solution (0 Ca2+ plus 0.2 mM EGTA), noradrenaline (10 microM) and caffeine (10 mM) induced only a single, transient contraction in artery strips, while 5-HT (10 microM) failed to induce any response. 2. In strips of mesenteric artery which had been permeabilized with Staphylococcus alpha-toxin and bathed in Ca(2+)-free mock intracellular solution, noradrenaline (10 microM), caffeine (10 mM) and D-myo-inositol (1,4,5)-trisphosphate (IP3, 100 microM), but not 5-HT (10 or 100 microM) induced a transient contraction. In contrast to the non-permeabilized strips, contractions to noradrenaline, caffeine and IP3 were restored by prior incubation (10 min) in solution containing 0.08 microM Ca2+. The contractions to noradrenaline and IP3 in permeabilized muscle strips required the presence of 100 microM guanosine 5'-triphosphate (GTP), although in the absence of Ca2+. GTP alone did not induce contraction. 3. Exposure of permeabilized mesenteric artery strips to IP3 significantly reduced the subsequent contractile responses to caffeine. Contractile responses to caffeine and IP3 were abolished by the Ca(2+)-ATPase inhibitor, thapsigargin (1 microM). 4. Ca2+ (0.1-10 microM) induced concentration-dependent contraction in permeabilized artery strips. In strips which were submaximally contracted with 0.5 microM Ca2+/100 microM GTP, the subsequent addition of 5-HT (10 microM) stimulated further contraction. The protein kinase C inhibitor, H-7 (1 microM) abolished the 5-HT/GTP-induced contraction, but did not alter the contraction to Ca2+. 5. In non-permeabilized, endothelium-denuded segments of rabbit mesenteric artery bathed in Ca2+-replete Krebs solution, noradrenaline (10 microM) stimulated a rapid, transient accumulation of IP3. 5-HT(100 microM) failed to stimulate IP3 accumulation during exposure periods of up to 5 min. 5-HT (100 microM)did stimulate IP3 accumulation if the external K+ concentration was raised (to around 25 mM). This concentration of K+ alone did not stimulate IP3 production and the 5-HT-stimulated IP3 accumulation in the presence of elevated extracellular [K+] was abolished by the alpha l-adrenoceptor antagonist, prazosin(O.1 microM).6. These results suggest that intracellular Ca2+ release does not play an important role in 5-HT-induced smooth muscle contraction in the rabbit mesenteric artery. This is despite the fact that a significant intracellular Ca2+ pool is present in these cells, which can be discharged by either noradrenaline or IP3.However, 5-HT did stimulate smooth muscle contraction in the presence of raised intracellular calcium,suggesting that a component of the contraction to 5-HT will reflect an increase in myofilament Ca2+sensitivity, possibly due to the activation of protein kinase C.
...
PMID:Importance of inositol (1,4,5)-trisphosphate, intracellular Ca2+ release and myofilament Ca2+ sensitization in 5-hydroxytryptamine-evoked contraction of rabbit mesenteric artery. 800 97

The goal of the present paper was to investigate 5-hydroxytryptamine (5HT)2A and 5HT2C receptor regulation of ion transport in fibroblast cell lines transfected with these receptors. Na+/K(+)-ATPase and Na+/K+/2Cl- cotransport were measured with 86Rb+ as a surrogate for K+ uptake. Serotonin agonists had no effect on Na+/K(+)-ATPase activity in either cell line. Bumetanide, an antagonist of Na+/K+/2Cl- cotransport, almost completely blocked ouabain-insensitive K+ uptake in both cell lines, with an IC50 of about 1 microM. 36Cl- uptake was 2-fold greater than 86Rb+ uptake, consistent with the expected 2:1 stoichiometry. In addition, the Cl-/HCO3- uptake blocker 4,4'-diisothiostilbene-2,2'-disulfonic acid had no effect on Cl- uptake. The 5HT2A/2C receptor agonist (-)-2,5-dimethoxy-4-bromoamphetamine increased ouabain-insensitive K+ uptake, and this effect was blocked by bumetanide. The receptor antagonists mianserin and mesulergine, but not spiperone, blocked (-)-2,5-dimethoxy-4-bromoamphetamine responses in fibroblasts transfected with 5HT2C receptors, and all three antagonists blocked the effects in cells expressing 5HT2A receptors. Ouabain-insensitive 22Na+ uptake was similarly affected. 5HT receptor-related actions were not observed in untransfected parent NIH/3T3 fibroblasts. Thus, we have demonstrated that 5HT2C and 5HT2A receptors are linked to activation of Na+/K+/2Cl- cotransport in transfected fibroblasts. This activity may be a factor in the pharmacological actions of 5HT agonists and antagonists.
...
PMID:5-Hydroxytryptamine type 2A and 2C receptors linked to Na+/K+/Cl- cotransport. 819 Jan 14

The effect of a rise in intracellular Na+ concentration ([Na+]cyt) on the amount of Ca2+ in intracellular stores was studied in vascular smooth muscle cells from the A7r5 line. The relative amount of stored Ca2+ was estimated in fura 2-loaded cells by the rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) evoked by Ca2+ release from the sarcoplasmic reticulum (SR). To improve the detection of released Ca2+, extrusion of Ca2+ from the cytosol was minimized by using nominally Na+/Ca(2+)-free medium containing 0.5 mM La3+ [for vasoconstrictor experiments, the medium contained 0.5 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and no La3+]. Ca2+ release was triggered by thapsigargin (TG), an SR Ca(2+)-ATPase inhibitor, and by the vasoconstrictors arginine vasopressin (AVP) and serotonin (5-HT). Incubation with 1-3 mM ouabain for 20 min, which raises [Na+]cyt from 4.4 to 9.0 mM, increased "resting" [Ca2+]cyt only slightly (from 87 to 122 nM). However, ouabain greatly augmented the release of Ca2+ evoked by TG [from 639 nM (control) to 1,021 nM], by AVP (from 993 to 1,597 nM), and by 5-HT (from 559 to 1,486 nM). Ouabain-induced augmentation of TG-evoked Ca2+ release was not affected by 10 microM verapamil; this implies that the effect of ouabain was not due to Ca2+ entry through voltage-gated Ca2+ channels. The response to TG was not augmented when ouabain was applied for 20 min in Na(+)-free medium (Na+ replaced by equimolar N-methyl-D-glucamine) to prevent [Na+]cyt from rising.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Increased intracellular Na+ augments mobilization of Ca2+ from SR in vascular smooth muscle cells. 830 27

Digitalis glycoside-like properties of the Bufo marinus toad crude venom and one of its constituents, bufalin, were studied in various assay systems. In concentrations 0.3-30 micrograms/ml crude venom increased the contractility of isolated electrically driven rat atria, constricted rat aortic rings, inhibited ouabain-sensitive Na+,K(+)-ATPase in rat erythrocytes and the Na+,K(+)-pump in rat aorta, and cross-reacted with antidigoxin antibody from the dissociation enhanced lanthanide fluoroimmunoassay (DELFIA). These effects were unaffected by adrenoceptor blockers and the 5-HT antagonist, deseril, but were blocked by antidigoxin antibody. Bufalin (10-30 microM) increased myocardial contractility and inhibited Na+,K(+)-ATPase in rat erythrocytes similarly to crude Bufo marinus venom. In rat aorta bufalin showed weak and delayed vasoconstrictor activity which was antagonized by 2 microM phentolamine, and had a biphasic effect on the Na+,K(+)-pump; 0.5-1.0 microM bufalin stimulated the pump, while higher concentrations inhibited its activity. Although the effects of bufalin were blocked by antidigoxin antibody, bufalin showed very low digoxin-like immunoreactivity in the DELFIA. These observations suggest that, in addition to bufalin, Bufo marinus venom contains at least one more digitalis-like steroid with significant intrinsic vasoconstrictor activity which, unlike bufalin, constricts the blood vessels acting directly via inhibition of the sodium pump in the vascular smooth muscle membrane.
...
PMID:Digitalis-like and vasoconstrictor effects of endogenous digoxin-like factor(s) from the venom of Bufo marinus toad. 838 9

We have utilized polarized epithelial cells stably expressing neurotransmitter transporters to analyze the sorting behavior of these membrane proteins. The transporters for serotonin (5-HT), dopamine (DA), and norepinephrine (NE) are expected to be present in situ in the most distal extremities of axonal membranes, where they terminate the action of their biogenic amine substrates. Both Madin-Darby canine kidney (MDCK) and LLC-PK1 cells were stably transfected with cDNAs encoding either the rat 5-HT transporter (SERT), the human NE transporter (NET), or the rat or human DA transporter (DAT). These cells were grown on permeable filter supports, and the transporters were localized by three independent techniques. Confocal immunofluorescence microscopy indicated that each of the transporters expressed in LLC-PK1 cells was sorted to the basolateral membrane, co-localizing with the Na+/K+-ATPase. In MDCK cells, however, DAT was located primarily on the apical surface, while SERT and NET were found on the basolateral membranes. Cell surface biotinylation using an impermeant biotinylating reagent confirmed the immunocytochemistry results. Thus, SERT and NET in MDCK cells were labeled more efficiently from the basolateral medium than the apical medium, and DAT in MDCK cells was labeled more efficiently from the apical side than the basolateral side. Transport measurements in transfected MDCK cells agreed with the immunocytochemistry and biotinylation results. These results suggest the existence of cell-specific mechanisms that discriminate between neurotransmitter transporters for surface expression and render unlikely any simple hypothesis that sorting mechanisms in neurons and epithelia are identical.
...
PMID:Cell-specific sorting of biogenic amine transporters expressed in epithelial cells. 866 73

1. 5-Hydroxytryptamine (5-HT) is antinatriuretic. Since this effect of 5-HT is not accomplished by changes in glomerular haemodynamics, we have examined in this study whether 5-HT may influence sodium excretion by affecting the Na+, K(+)-ATPase activity in renal cortical tubules. 2. Na+, K(+)-ATPase activity was determined as the rate of [32P]-ATP hydrolysis in renal cortical tubules in suspension. Basal Na+, K(+)-ATPase activity in renal tubules was 4.8 +/- 0.4 mumol Pi mg-1 protein h-1 (n = 8). The 5-HT1A receptor agonist, (+/-)-8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT) (10 to 3000 nM) induced a concentration-dependent increase (P < 0.05) in Na+, K(+)-ATPase activity with an EC50 value of 355 nM (95% confidence limits: 178, 708). Maximal stimulation elicited by 3000 nM of 8-OH-DPAT was antagonized by the selective 5-HT1A receptor antagonist, (+)-WAY 100135 10 to 1000 nM) with an IC50 value of 20 nM (14, 29); 0.3 microM (+)-WAY 100135 completely abolished (P < 0.01) the stimulatory effect of 8-OH-DPAT. The stimulatory effect of 8-OH-DPAT was found to be time-dependent (15 +/- 2% and 66 +/- 7% increase at 2.5 and 5.0 min, respectively). The 5-HT2 receptor agonist alpha-methyl-5-HT (100 to 3000 nM) did not induce any significant changes in Na+, K(+)-ATPase activity (5.0 +/- 1.5 mumol Pi mg-1 protein h-1; n = 4). 3. The stimulatory effect 8-OH-DPAT was absent when homogenates were used. Stimulation occurred at a Vmax concentration (70 mM) of sodium supporting the notion that stimulation occurs independently of increasing sodium permeability. 4. The inhibitory effect of dopamine (P < 0.05) on Na+, K(+)-ATPase activity was blunted by co-incubation with 8-OH-DPAT (0.5 microM). 5. It is concluded that activation of 5-HT1A receptors increases Na+, K(+)-ATPase activity in renal cortical tubules; this effect may represent an important cellular mechanism, at the tubule level, responsible for the antinatriuretic effect of 5-HT.
...
PMID:Antagonistic actions of renal dopamine and 5-hydroxytryptamine: increase in Na+, K(+)-ATPase activity in renal proximal tubules via activation of 5-HT1A receptors. 888 16

Tracheal strips from normal and actively sensitized guinea pigs were studied to determine the responses to serotonin (5-hydroxytryptamine, 5-HT; 1 nM-0.1 mM) and ouabain (0.1 microM-0.1 mM), and the effects of increasing the extracellular calcium (Cao) concentration on tonic contractions elicited by 5-HT. Sensitized trachea exhibited an increased responsiveness and sensitivity to 5-HT and ouabain. Increases in Cao to achieve final concentrations of 5, 10 and 20 mM caused concentration-related relaxations of normal and sensitized tissues contracted to a similar plateau level with 5-HT. Inhibition of the Na+/K(+)-ATPase by ouabain (10 microM) reversed the effects of Cao from relaxation to contraction in normal and sensitized tissues contracted with 5HT. Sensitized preparations showed reduced relaxations in response to Cao (10-20 mM), and sensitized, ouabain-treated, trachea showed augmented contractions to Cao (10-20 mM) when compared to normal tissues. These results demonstrate a decreased membrane-stabilizing effect of Cao in sensitized trachea and the implication of the Na+/K(+)-ATPase in the regulation of membrane stability by Cao, suggesting a possible relevance to those mechanisms underlying airway hyperreactivity.
...
PMID:Effect of serotonin and calcium in normal and sensitized guinea pig isolated trachea. 890 Apr 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---