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)

It has recently been discovered that both mineralocorticoid (MC) and glucocorticoid (GC) hormones can stimulate electrogenic Na+ absorption by mammalian collecting duct cells in culture. In primary cultures of rat inner medullary collecting duct (IMCD) cells, 24-h incubation with either MC or GC agonist stimulates Na+ transport approximately threefold. We have now determined that the effects were not additive, but the time courses were different. As aldosterone is known to stimulate citrate synthase, Na+/K+ ATPase activity, and ouabain binding in cortical collecting duct principal cells, we determined the effects of steroids on these parameters in IMCD cells. MC and GC agonists both produced a small increase in citrate synthase activity. There was no increase in Na+/K+ ATPase activity but specific ouabain binding was increased more than two-fold by either agonist. To determine the role of apical Na+ entry in the steroid-induced effects, the Na+ channel inhibitor, benzamil, was used. Benzamil did not alter the stimulation of citrate synthase activity by either steroid. In contrast, GC stimulation of ouabain binding was prevented by benzamil, whereas MC stimulation was not. We conclude that there are differences in the way that MC and GC hormones produce an increased Na+ transport. Both appear to produce translocation (or activation) of pumps into the basolateral membrane. GC stimulation of pump translocation requires increased Na+ entry whereas MC stimulation does not.
...
PMID:Cellular responses to steroids in the enhancement of Na+ transport by rat collecting duct cells in culture. Differences between glucocorticoid and mineralocorticoid hormones. 132 98

The relaxant effects of amiloride and its analogues, benzamil, 5-(N,N-diethyl)-amiloride (DEAM) and 5-(N-ethyl-N-isopropyl)-amiloride (EIAM), were investigated using smooth muscle of guinea-pig taenia caeci and chicken gizzard. High K+-induced contractions of intact taenia and gizzard were inhibited by these compounds (1-100 microM) with the order of potency; benzamil greater than or equal to EIAM greater than DEAM greater than amiloride. Contractions of permealized taenia and gizzard were also inhibited by these compounds at concentrations 8-35 times higher than those needed to inhibit the contractions of intact tissues. These compounds inhibited 20 K myosin light chain (MLC) phosphorylation at the concentrations needed to inhibit the contraction in the permealized muscles. Calmodulin (CaM) activity, as monitored by erythrocyte membrane (Ca2+ + Mg2+)-ATPase and phosphodiesterase activities, was inhibited by DEAM and EIAM at similar concentrations as those to inhibit the MLC phosphorylation. Benzamil also inhibited CaM activity at concentrations 4-8 times higher than those required to inhibit MLC phosphorylation. However, amiloride failed to inhibit CaM activity. Among these compounds, amiloride and benzamil inhibited Ca2+/CaM-independent MLC phosphorylation due to trypsin-treated MLC kinase. Taenia tissue gradually accumulated these compounds and the tissue/medium ratio exceeded 3.5-17 after a 3-hr incubation period. These results indicate that amiloride and its analogues inhibit smooth muscle contraction mainly by the direct inhibition of MLC phosphorylation. The inhibitory effect of amiloride may be attributable to the inhibition of MLC kinase, whereas the inhibitory effect of DEAM and EIAM may largely be attributable to the inhibition of CaM. Benzamil may inhibit contraction by the inhibition of both MLC kinase and CaM. Differences in the drug-sensitivity between intact and permealized tissues may be attributable to the difference in drug accumulation by the cell.
...
PMID:Direct inhibition of contractile apparatus by analogues of amiloride in the smooth muscle of guinea-pig taenia caecum and chicken gizzard. 293 May 91

The cellular mechanism of luminal acidification (bicarbonate reabsorption) was studied in cortical distal tubules of rat kidney. The stopped-flow microperfusion technique was applied to early distal (ED) and late distal (LD) segments, perfused with bicarbonate Ringer solution to which specific inhibitors were added, to measure bicarbonate reabsorption [HCO3 flux (JHCO3)]. pH and transepithelial potential difference (Vt) were recorded by double-barreled H+ exchange resin/reference (1 M KCl) electrodes. Amiloride increased stationary pH and reduced Vt in both early and late segments. Hexamethylene-amiloride (HMA), a specific Na(+)-H+ exchange blocker, reduced JHCO3 in both segments (ED by 43.6 and LD by 40.3%) without affecting Vt. Benzamil, an Na(+)-channel blocker, reduced Vt by 75.9 in ED and 74.9% in LD but had no significant effect on acidification in both segments. The specific inhibitor of H(+)-ATPase, bafilomycin A1, inhibited LD JHCO3 at a concentration of 2 x 10(-7) M by 49%, but ED was inhibited by 24% only at 2 x 10(-6) M. Sch-28080, an inhibitor of gastric H(+)-K(+)-ATPase, reduced JHCO3 by 35% in LD of K(+)-depleted rats but not in control rats and had no effect on ED. These data indicate that, in ED, bicarbonate reabsorption is mediated mostly by Na(+)-H+ exchange. In LD, there is evidence for contribution of Na(+)-H+ exchange, vacuolar H(+)-ATPase, and H(+)-K(+)-ATPase (in K(+)-depleted rats) to bicarbonate reabsorption.
...
PMID:Mechanism of acidification along cortical distal tubule of the rat. 814 23

1. An analog of L-glutamic acid, threo-beta-hydroxy-L-glutamic acid (threo-L-BHGA), was applied locally to the giant neuron of an Achatina snail by pneumatic brief pressure ejection and induced an outward current (Iout) on the ventral-left cerebral distinct neurone (v-LCDN). The present study aimed to elucidate the ionic mechanisms of the Iout caused by threo-L-BHGA (ItL-BHGA) of v-LCDN and the effects of ouabain on this current under voltage clamp. 2. The reversal potentials of ItL-BHGA (EtL-BHGA) of v-LCDN in varied K+o were fitted to the Nernst equation as ItL-BHGA = IK (K+ current) and were almost unchanged in Cl-o-free and Na+o-reduced (20% of normal) states. The ItL-BHGA is due to the increase in permeability of the neuromembrane to K+(K(+)-dependent) and is neither Na(+)- nor Cl-(-)-dependent. K(+)-channel blockers, a mixture of tetraethyl-ammonium (TEA) and 4-amino-pyridine (4-AP), blocked ItL-BHGA mainly in a noncompetitive and partly in an uncompetitive manner. 3. Unexpectedly, ItL-BHGA of v-LCDN was almost abolished in the Na+o-free state and significantly reduced in the Cl-o-free state. However, an Na(+)-channel blocker, tetrodotoxin, showed a tendency to enhance ItL-BHGA. On the other hand, ItL-BHGA was enhanced in K+o-free state. 4. Ouabain markedly inhibited ItL-BHGA in both noncompetitive and uncompetitive manners. Benzamil, an inhibitor of the Na(+)-Ca2+ exchange applied simultaneously with ouabain could not prevent ouabain inhibition on ItL-BHGA. The currents induced by other putative neurotransmitters, including a K(+)-dependent Iout caused by dopamine on v-LCDN, were not affected by ouabain. 5. According to our previous study, the threo-L-BHGA receptors are not linked with protein kinases or calmodulin. Then, ItL-BHGA could be produced by the receptor K+ channel complex or the receptor-G-protein-K+ channel combination. The present results indicate that the ATPase activity inhibited by ouabain and the presence of extracellular Na+ and Cl- are needed for threo-L-BHGA to activate the K(+)-dependent structure. Furthermore, the K+o-free state, which inactivates the Na(+)-K+ pump, and tetrodotoxin, which suppresses the Na+ channel at least partly, did not affect the structure to be activated.
...
PMID:Ouabain-sensitive K(+)-dependent outward current caused by threo-beta-hydroxy-L-glutamic acid on a snail neuron. 935 13

Treatment of Madin-Darby canine kidney (MDCK) cells with the peptide hormone angiotensin II (Ang II) results in an increase in the concentrations of cytosolic free calcium ([Ca(2+)](i)) and sodium ([Na(+)](i)) with a concomitant decrease in cytosolic free Mg(2+) concentration ([Mg(2+)](i)). In the present study we demonstrate that this hormone-induced decrease in [Mg(2+)](i) is independent of [Ca(2+)](i) but dependent on extracellular Na(+). [Mg(2+)](i), [Ca(2+)](i), and [Na(+)](i) were measured in Ang II-stimulated MDCK cells by fluorescence digital imaging using the selective fluoroprobes mag-fura-2AM, fura-2AM, and sodium-binding benzofuran isophthalate (acetoxymethyl ester), respectively. Ang II decreased [Mg(2+)](i) and increased [Na(+)](i) in a dose-dependent manner. These effects were inhibited by irbesartan (selective AT(1) receptor blocker) but not by PD123319 (selective AT(2) receptor blocker). Imipramine and quinidine (putative inhibitors of the Na(+)/Mg(2+) exchanger) and removal of extracellular Na(+) abrogated Ang II-mediated [Mg(2+)](i) effects. In cells pretreated with thapsigargin (reticular Ca(2+)-ATPase inhibitor), Ang II-stimulated [Ca(2+)](i) transients were attenuated (p < 0.01), whereas agonist-induced [Mg(2+)](i) responses were unchanged. Clamping the [Ca(2+)](i) near 50 nmol/liter with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) inhibited Ang II-induced [Ca(2+)](i) increases but failed to alter Ang II-induced [Mg(2+)](i) responses. Benzamil, a selective blocker of the Na(+)/Ca(2+) exchanger, inhibited [Na(+)](i) but not [Mg(2+)](i) responses. Our data demonstrate that in MDCK cells, AT(1) receptors modulate [Mg(2+)](i) via a Na(+)-dependent Mg(2+) transporter that is not directly related to [Ca(2+)](i). These data support the notion that rapid modulation of [Mg(2+)](i) is not simply a result of Mg(2+) redistribution from intracellular buffering sites by Ca(2+) and provide evidence for the existence of a Na(+)-dependent, hormonally regulated transporter for Mg(2+) in renally derived cells.
...
PMID:Angiotensin II type I receptor modulates intracellular free Mg2+ in renally derived cells via Na+-dependent Ca2+-independent mechanisms. 1127 87

The purpose of this study was to physiologically characterize the basolateral Na(+)/Ca(2+) exchanger (NCX) in basolateral membrane vesicles (BLMVs) of hepatopancreas and antennal gland of intermolt crayfish. Conditions were optimized to measure Na(+)-dependent Ca(2+) uptake and retention in the BLMV including use of intravesicular (IV) oxalate and measuring initial uptake rates at 20 s. Na(+)-dependent Ca(2+) uptake rate into BLMV was temperature insensitive. Na(+)-dependent Ca(2+) uptake rate was dependent upon free Ca(2+) with saturable Michaelis-Menten kinetics determined as follows: hepatopancreas, maximal uptake rate (J(max))=2.45 nmol/mg per min, concentration at which carrier operates at half-maximal uptake rate (K(m))=0.69 microM Ca(2+); antennal gland, J(max)=13.2 nmol/mg per min, K(m)=0.59 microM Ca(2+). The two vesicle populations exhibited different sensitivity to putative NCX inhibitors. Benzamil had no effect on Na(+)-dependent Ca(2+) uptake rate in hepatopancreas; in antennal gland it was inhibitory at concentrations up to 30 microM and was stimulatory at higher concentrations. Conversely the inhibitor quinacrine was inhibitory at 10 microM in hepatopancreas and was stimulatory at 1000 microM; meanwhile it was ineffective in antennal gland BLMV. Short circuiting the BLMV had no effect on Na(+)-dependent Ca(2+) uptake rate suggesting that the process may be electroneutral. Compared with another prominent basolateral transporter in hepatopancreas the plasma membrane Ca(2+) ATPase (PMCA), the NCX has 70-fold greater J(max) (at comparable temperature) and a lower affinity. In antennal gland the NCX has 40-fold greater J(max) and a lower affinity. In hepatopancreas and antennal gland BLMV NCX appears to determine the rate of basolateral Ca(2+) efflux in intermolt.
...
PMID:Physiological characterization of the Na(+)/Ca(2+) exchanger (NCX) in hepatopancreatic and antennal gland basolateral membrane vesicles isolated from the freshwater crayfish Procambarus clarkii. 1181 24

Recent studies have implicated epithelial Na+ channels (ENaC) in myogenic signaling. The present study was undertaken to determine if ENaC and/or Na+ entry are involved in the myogenic response of the rat afferent arteriole. Myogenic responses were assessed in the in vitro hydronephrotic kidney model. ENaC expression and membrane potential responses were evaluated with afferent arterioles isolated from normal rat kidneys. Our findings do not support a role of ENaC, in that ENaC channel blockers did not reduce myogenic responses and ENaC expression could not be demonstrated in this vessel. Reducing extracellular Na+ concentration ([Na+]o; 100 mmol/l) did not attenuate myogenic responses, and amiloride had no effect on membrane potential. Benzamil, an inhibitor of ENaC that also blocks Na+/Ca2+ exchange (NCX), potentiated myogenic vasoconstriction. Benzamil and low [Na+]o elicited vasoconstriction; however, these responses were attenuated by diltiazem and were associated with significant membrane depolarization, suggesting a contribution of mechanisms other than a reduction in NCX. Na+ repletion induced a vasodilation in pressurized afferent arterioles preequilibrated in low [Na+]o, a hallmark of NCX, and this response was reduced by 10 micromol/l benzamil. The dilation was eliminated, however, by a combination of benzamil plus ouabain, suggesting an involvement of the electrogenic Na+-K+-ATPase. In concert, these findings refute the premise that ENaC plays a significant role in the rat afferent arteriole and instead suggest that reducing [Na+](o) and/or Na+ entry is coupled to membrane depolarization. The mechanisms underlying these unexpected and paradoxical effects of Na+ are not resolved at the present time.
...
PMID:Effects of amiloride, benzamil, and alterations in extracellular Na+ on the rat afferent arteriole and its myogenic response. 1849

The cellular and molecular mechanisms that underlie acquired changes in Ca(2+) dynamics of different neuronal compartments are important in the induction and maintenance of epileptiform activity. Simultaneous electrophysiology and Ca(2+) imaging techniques were used to understand the basic properties of dendritic Ca(2+) signaling in rat subicular pyramidal neurons during epileptiform activity. Distance-dependent changes in the Ca(2+) decay kinetics locked to spontaneous epileptiform discharges and back-propagating action potentials were observed in the apical dendrites. A decrement in the mean tau value of Ca(2+) decay was observed in distal parts (95-110 mum) of the apical dendrites compared with proximal segments (30-45 mum) in in-vitro epileptic conditions but not in control. Pharmacological agents that block Ca(2+) transporters, i.e. Na(+)/ Ca(2+) exchangers (Benzamil), plasma membrane Ca(2+)-ATPase pumps (Calmidazolium) and smooth endoplasmic reticulum Ca(2+)-ATPase pumps (Thapsigargin), were applied locally to the proximal and distal part of the apical dendrites in both experimental conditions to understand the molecular aspects of the Ca(2+) extrusion mechanisms. The relative contribution of Na(+)/Ca(2+) exchangers in Ca(2+) extrusion was higher in the distal apical dendrites in the in-vitro epileptic condition and this property modulated the excitability of the neuron in simulation. The Ca(2+) homeostatic mechanisms that restore normal Ca(2+) levels could play a major neuroprotective role in the distal dendrites that receive synaptic inputs.
...
PMID:Epileptiform activity induces distance-dependent alterations of the Ca2+ extrusion mechanism in the apical dendrites of subicular pyramidal neurons. 1904 66

To elucidate the role of epithelial sodium channels (ENaCs) and Na(+)-K(+)-ATPase in Na(+) transport by the choroid plexus, we studied ENaC expression and Na(+) transport in the choroid plexus. Lateral ventricle choroid plexuses were obtained from young male Wistar, Dahl salt-resistant (SS.BN13), and Dahl salt-sensitive (SS/MCW) rats on a regular (0.3%) or high- (8.0%) salt diet. The effects of ENaC blocker benzamil and Na(+)-K(+)-ATPase blocker ouabain on sodium transport were evaluated by measuring the amounts of retained (22)Na(+) and by evaluating intracellular [Na(+)] with Sodium Green fluorescence. In Wistar rats, ENaC distribution was as follows: microvilli, 10% to 30%; cytoplasm, 60% to 80%; and basolateral membrane, 5% to 10%. Benzamil (10(-8) m) decreased (22)Na(+) retention by 20% and ouabain (10(-3) m) increased retention by 40%, whereas ouabain and benzamil combined caused no change. Similar changes were noted in intracellular [Na(+)]. In Dahl rats on a regular salt diet, intracellular [Na(+)] was similar, but the amount of retained (22)Na(+) was less in sensitive versus resistant rats. High salt did not affect ENaC mRNA or protein, nor the benzamil induced decreases in retained (22)Na(+) or intracellular [Na(+)] in either strain. However, high salt increased intracellular [Na(+)] and attenuated the increase in uptake of (22)Na(+) by ouabain in resistant but not sensitive rats, suggesting a decrease in Na(+)-K(+)-ATPase activity only in resistant rats. These findings suggest that both ENaC and Na(+)-K(+)-ATPase regulate Na(+) transport in the choroid plexus. Aberrant regulation of Na(+) transport and of Na(+)-K(+)-ATPase activity, but not of ENaCs, might contribute to the increase in cerebrospinal fluid [Na(+)] in Dahl salt-sensitive rats on a high-salt diet.
...
PMID:Sodium transport in the choroid plexus and salt-sensitive hypertension. 1963 91

This study examined the mechanism of release of endogenous acetylcholine (ACh) in rabbit renal cortex by applying a microdialysis technique. In anesthetized rabbits, a microdialysis probe was implanted into the renal cortex and perfused with Ringer's solution containing high potassium concentration, high sodium concentration, a Na⁺/K⁺-ATPase inhibitor (ouabain), or an epithelial Na⁺ channel blocker (benzamil). Dialysate samples were collected at baseline and during exposure to each agent, and ACh concentrations in the samples were measured by high-performance liquid chromatography. High potassium had no effect on renal ACh release. High sodium increased dialysate ACh concentrations significantly. Ouabain increased dialysate ACh concentration significantly. Benzamil decreased dialysate ACh concentrations significantly both at baseline and under high sodium. The finding that high potassium-induced depolarization does not increase ACh release suggests that endogenous ACh is released in renal cortex mainly by non-neuronal mechanism. Sodium ion transport may be involved in the non-neuronal ACh release.
...
PMID:Sodium ion transport participates in non-neuronal acetylcholine release in the renal cortex of anesthetized rabbits. 2766 58


1

---