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)

Electrogenic Na absorption, independent of either nutrients or other ions, occurs in the rabbit ileum. However, unlike electrogenic Na absorption in the distal colon and other tight epithelia, this ileal transport system is not inhibited by amiloride. Because of this amiloride insensitivity, ileal electrogenic Na absorption has been poorly characterized. To more clearly delineate the underlying mechanisms of this pathway, we examined the effects of phenamil, an amiloride analogue, on ion fluxes and electrical parameters in rabbit ileum in vitro under short-circuit conditions. Phenamil has been shown to have a high affinity for Na channels, but minimal effect on Na-H exchange. Amiloride (10(-8) through 10(-4) M) had a minimal effect on short-circuit current. In contrast, phenamil induced a significant decrease in short-circuit current; the maximal effect was seen at 10(-4) M phenamil. There was an associated decrease in conductance at 10(-4) M phenamil. Ion flux studies were performed in normal, chloride-free and bicarbonate-free Ringer's solution; under each condition, 10(-4) M phenamil inhibited mucosal-to-serosal Na flux, net Na flux, and short-circuit current without significantly altering other fluxes. Phenamil did not inhibit the electrical response to either 10 mM glucose or 1 mM theophylline, indicating that the drug did not block either nutrient-coupled electrogenic Na absorption or electrogenic Cl secretion, and did not inhibit sodium-potassium-stimulated adenosine triphosphatase. These results demonstrate that electrogenic Na absorption in rabbit ileum may be blocked by the amiloride analogue phenamil, suggesting that, in this epithelium, Na absorption may occur via Na channels in which the amiloride-binding site has been significantly altered.
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PMID:Phenamil inhibits electrogenic sodium absorption in rabbit ileum. 253 78

The branchial uptake mechanism of the nonessential heavy metal silver from very dilute media by the gills of freshwater rainbow trout was investigated. At concentrations >36 nM AgNO(3), silver rapidly entered the gills, reaching a peak at 1 h, after which time there was a steady decline in gill silver concentration and a resulting increase in body silver accumulation. Below 36 nM AgNO(3), there was only a very gradual increase in gill and body silver concentration over the 48-h exposure period. Increasing water sodium concentration ([Na(+)]; 0.05 to 21 mM) significantly reduced silver uptake, although, in contrast, increasing ambient [Ca(2+)] or [K(+)] up to 10 mM did not reduce silver uptake. Kinetic analysis of silver uptake at varying [Na(+)] showed a significant decrease in maximal silver transport capacity (173 +/- 34 pmol. g(-1). h(-1) at 0.1 mM [Na(+)] compared with 35 +/- 9 at 13 mM [Na(+)]) and only a slight decrease in the affinity for silver transport (K(m); 55 +/- 27 nM at 0.1 mM [Na(+)] compared with 91 +/- 47 nM at 13 mM [Na(+)]). Phenamil (a specific blocker of Na(+) channels), at a concentration of 100 microM, blocked Na(+) uptake by 78% of control values (58% after washout), and bafilomycin A(1) (a specific blocker of V-type ATPase), at a concentration of 2 microM, inhibited Na(+) uptake by 57% of control values, demonstrating the presence of a proton-coupled Na(+) channel in the apical membrane of the gills. Phenamil (after washout) and bafilomycin A(1) also blocked silver uptake by 62 and 79% of control values, respectively, indicating that Ag(+) is able to enter the apical membrane via the proton-coupled Na(+) channel.
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PMID:Mechanism of branchial apical silver uptake by rainbow trout is via the proton-coupled Na(+) channel. 1056 11

The mechanism of Pb-induced disruption of Na(+) and Cl(-) balance was investigated in the freshwater rainbow trout (Oncorhynchus mykiss). Na(+) and Cl(-) influx rates were reduced immediately in the presence of 2.40 +/- 0.24 and 1.25 +/- 0.14 muM Pb, with a small increase in efflux rates occurring after 24-h exposure. Waterborne Pb caused a significant decrease in the maximal rate of Na(+) influx without a change in transporter affinity, suggesting a noncompetitive disruption of Na(+) uptake by Pb. Phenamil and bafilomycin markedly reduced Na(+) influx rate but did not affect Pb accumulation at the gill. Time-course analysis in rainbow trout exposed to 0, 0.48, 2.4, and 4.8 microM Pb revealed time- and concentration-dependent branchial Pb accumulation. Na(+)-K(+)-ATPase activity was significantly reduced, with 4.8 microM exposure resulting in immediate enzyme inhibition and 0.48 and 2.4 microM exposures inhibiting activity by 24 h. Reduced activity was weakly correlated with gill Pb accumulation after 3- and 8-h exposures; this relationship strengthened by 24 h. Reduced Na(+) uptake was correlated with gill Pb burden after exposures of 3, 8, and 24 h. Immediate inhibition of branchial carbonic anhydrase activity occurred after 3-h exposure to 0.82 +/- 0.05 or 4.30 +/- 0.05 microM Pb and continued for up to 24 h. We conclude that Pb-induced disruption of Na(+) and Cl(-) homeostasis is in part a result of rapid inhibition of carbonic anhydrase activity and of binding of Pb with Na(+)-K(+)-ATPase, causing noncompetitive inhibition of Na(+) and Cl(-) influx.
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PMID:Mechanisms behind Pb-induced disruption of Na+ and Cl- balance in rainbow trout (Oncorhynchus mykiss). 1601 49

The bacterial flagellar type III export apparatus utilizes ATP and proton motive force (PMF) to transport flagellar proteins to the distal end of the growing flagellar structure for self-assembly. The transmembrane export gate complex is a H+-protein antiporter, of which activity is greatly augmented by an associated cytoplasmic ATPase complex. Here, we report that the export gate complex can use sodium motive force (SMF) in addition to PMF across the cytoplasmic membrane to drive protein export. Protein export was considerably reduced in the absence of the ATPase complex and a pH gradient across the membrane, but Na+ increased it dramatically. Phenamil, a blocker of Na+ translocation, inhibited protein export. Overexpression of FlhA increased the intracellular Na+ concentration in the presence of 100 mM NaCl but not in its absence, suggesting that FlhA acts as a Na+ channel. In wild-type cells, however, neither Na+ nor phenamil affected protein export, indicating that the Na+ channel activity of FlhA is suppressed by the ATPase complex. We propose that the export gate by itself is a dual fuel engine that uses both PMF and SMF for protein export and that the ATPase complex switches this dual fuel engine into a PMF-driven export machinery to become much more robust against environmental changes in external pH and Na+ concentration.
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PMID:The Bacterial Flagellar Type III Export Gate Complex Is a Dual Fuel Engine That Can Use Both H+ and Na+ for Flagellar Protein Export. 2694 26