Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00514 (Amiloride)
 1,513 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported that rabbit renal cortical collecting tubules can secrete bicarbonate in vitro (i.e., there can be net transport from bath to lumen, causing the concentration in the lumen to increase). Net bicarbonate secretion was observed most often when rabbits had been pretreated with NaHCO(3) and were excreting alkaline urine before being killed for experiments. The purpose of the present studies was to elucidate the mechanism involved by testing the effects of ion substitutions and drugs on collecting tubules that were secreting bicarbonate. Acetazolamide inhibited net bicarbonate secretion, suggesting that the process is dependent upon carbonic anhydrase. Net bicarbonate secretion also decreased when sodium in the perfusate and bath was replaced by choline, but not when chloride was replaced by nitrate or methylsulfate. Ouabain had no significant effect. Amiloride caused net bicarbonate secretion to increase. The rate of net secretion did not correlate with transepithelial voltage. The results are compared to those in turtle urinary bladders that also secrete bicarbonate. There are no direct contradictions between the results in the two tissues, i.e., in turtle bladders acetazolamide also inhibited bicarbonate secretion and ouabain had no effect. Nevertheless, it seems unlikely that net secretion of bicarbonate by collecting tubules involves specific exchange for chloride, as has been proposed for turtle bladders, because replacement of chloride by other anions did not inhibit bicarbonate secretion by collecting tubules. It was previously shown that the collecting tubules in vitro also may absorb bicarbonate, especially when the rabbits have been treated with NH(4)Cl and are excreting acid urine before being killed. The effects of drugs on net bicarbonate secretion found in the present studies are compared to their previously reported effects on net bicarbonate absorption and the possibility is discussed that bicarbonate absorption and secretion are independent processes, as was previously proposed for turtle bladders.
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PMID:Bicarbonate secretion by rabbit cortical collecting tubules in vitro. 65 4

The uptake of Cu+ by rat liver mitochondria is rapid and extensive. Respiration is stimulated by 10 microM Cu+ then inhibited and the inhibition could not be relieved with uncoupling agents. Collapse of the membrane potential is induced by 5-10 microM Cu+. These effects are partially inhibited by radical scavengers indicating the involvement of radical production in these events. Reduction of the GSH content and production of peroxidation products by higher amounts of Cu+ was also demonstrated. Swelling of non-respiring rat liver and heart mitochondria in sodium or lithium acetate was used to study effects of Cu+ on the Na+/H+ exchanger. Swelling is stimulated by 5-100 microM Cu+. In the presence of a radical scavenger the swelling is reduced. In sodium nitrate media diltiazem-sensitive stimulated swelling is observed. Amiloride was found to inhibit Cu(+)-induced efflux of Ca2+. At high concentrations of Cu+, a general increase in permeability was the dominant feature.
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PMID:Interaction of Cu+ with mitochondria. 166 75

Cholinergically stimulated Cl and HCO3 transport in perfused rabbit mandibular glands has been studied with extracellular anion substitution and administration of transport inhibitors. In glands perfused with HCO3-free solutions, replacement of Cl with other anions supported secretion in the following sequence: Br = greater than Cl greater than I = greater than NO3 greater than isethionate. Furosemide, 1.0 and 0.1 mmol/l, inhibited Cl-supported secretion by 97-99% and 70-78%, respectively. SITS, 0.1 mmol/l, had no effect and amiloride, 1.0 mmol/l, caused a 55-65% inhibition. Addition of SITS to amiloride-treated glands produced no further effect. In glands perfused with Cl-free solutions, but containing 25 mM HCO3, amiloride, 1.0 mmol/l, inhibited secretion by 95% and methazolamide, 0.1 mmol/l, by 55%. In glands perfused with solutions containing both HCO3 and Cl, furosemide had smaller effects than in glands perfused with solutions containing only Cl - a dose of 1.0 mmol/l inhibited 60% of the initial fast phase of secretion, and 90% of the later plateau phase, while a dose of 0.1 mmol/l inhibited 30% of the initial phase, but had no effect on the plateau. SITS, 0.1 mmol/l, actually stimulated secretion by about 30%, but when infused in addition to furosemide (0.1 mmol/l), it inhibited by about 20%. Amiloride (1.0 mmol/l) caused no inhibition. The results suggest that there are at least three distinct carriers in the rabbit mandibular gland. One is a furosemide-sensitive Na-coupled Cl (probably Na-K-2Cl) symport, responsible for the bulk of normal secretion. The others are an amiloride-sensitive Na-H antiport and a SITS-sensitive Cl-HCO3 antiport.
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PMID:Two independent anion transport systems in rabbit mandibular salivary glands. 379 20

The large increase in passive Na flux that occurs when dog red blood cells are caused to shrink is amiloride sensitive and inhibited when Cl is replaced by nitrate or thiocyanate. Activation and deactivation of this transport pathway by manipulation of cell volume is reversible. Brief treatment of the cells with 0.01-0.03% glutaraldehyde can cause the shrinkage-activated transporter to become irreversibly activated or inactivated, depending on the volume of the cells at the time of glutaraldehyde exposure. Thus, if glutaraldehyde is applied when the cells are shrunken, the amiloride-sensitive Na transporter is activated and remains so regardless of subsequent alterations in cell volume. If the fixative is applied to swollen cells, no amount of subsequent shrinkage will turn on the Na pathway. In its fixed state, the activated transporter is fully amiloride sensitive, but it is no longer inhibited when Cl is replaced by thiocyanate. The action of glutaraldehyde thus allows one to dissect the response to cell shrinkage into two phases. Activation of the pathway is affected by anions and is not prevented by amiloride. Once activated and fixed, the anion requirement disappears. Amiloride inhibits movement of Na through the activated transporter. These experiments demonstrate how a chemical cross-linking agent may be used to study the functional properties of a regulable transport pathway.
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PMID:Glutaraldehyde fixation of sodium transport in dog red blood cells. 643 17

We investigated the mechanism of Cl- transport in microvillus membrane vesicles isolated from Necturus kidneys. Cl- influx was insensitive to changes in membrane potential induced by K+ gradients and the K+ ionophore valinomycin, arguing against conductive Cl- transport. Inward gradients of Na+ or Na+ + K+ did not stimulate initial Cl- influx, arguing against direct Na+-Cl- or Na+-K+-Cl- cotransport. External Cl-, HCO3-, and NO3- each stimulated 36Cl efflux and inhibited 36Cl uptake, indicating anion exchange. Outward HCO3- gradients but not OH- gradients stimulated 36Cl influx, consistent with Cl- -HCO3- exchange. Cl- transport via anion exchange was inhibited by furosemide, bumetanide, and disulfonic stilbenes, but not by acetazolamide. External halides stimulated 36Cl efflux (Cl- = Br- greater than I- greater than F-) but the organic anions lactate, p-aminohippurate, and urate did not. Amiloride-sensitive Na+-H+ exchange was demonstrated. Finally, in the presence of a CO2/HCO3 buffer system, imposing an inward Na+ gradient caused a time-delayed stimulation of 36Cl uptake, consistent with indirect coupling of Na+-H+ and Cl- -HCO3- exchangers. We conclude that the parallel operation of Na+-H+ and Cl- -HCO3- exchangers rather than direct cotransport may account for the Na+-coupled uphill Cl- entry previously observed in the intact proximal tubular cell of Necturus.
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PMID:Cl- transport via anion exchange in Necturus renal microvillus membranes. 650 28

Sodium transport mechanisms were investigated in plasma membrane vesicles prepared from the medullary thick ascending limb of Henle's loop (TALH) of rabbit kidney. The uptake of 22Na into the plasma membrane vesicles was investigated by a rapid filtration technique. Sodium uptake was greatest in the presence of chloride; it was reduced when chloride was replaced by nitrate, gluconate or sulfate. The stimulation of sodium uptake by chloride was seen in the presence of a chloride gradient directed into the vesicle and when the vesicles were equilibrated with NaCl, KCl plus valinomycin so that no chemical or electrical gradients existed across the vesicle (tracer exchange experiments). Furosemide decreased sodium uptake into the vesicles in a dose-dependent manner only in the presence of chloride, with a Ki of around 5 X 10(-6) M. Amiloride, at 2 mM, had no effect on the chloride-dependent sodium uptake. Similarly, potassium removal had no effect on the chloride-dependent sodium uptake and furosemide was an effective inhibitor of sodium uptake in a potassium-free medium. The results show the presence of a furosemide-sensitive sodium-chloride cotransport system in the plasma membranes of the medullary TALH. There is no evidence for a Na+/H+ exchange mechanism or a Na+ -K+ -Cl- cotransport system. The sodium-chloride cotransport system would effect the uphill transport of chloride against its electrochemical potential gradient at the luminal membrane of the cell.
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PMID:Sodium-chloride transport in the medullary thick ascending limb of Henle's loop: evidence for a sodium-chloride cotransport system in plasma membrane vesicles. 685 22

The involvement of imidazoline receptors in modulation of noradrenaline release was investigated in the rabbit aorta preincubated with [3H]noradrenaline and superfused with physiological salt solution containing cocaine, corticosterone and propranolol. After blockade of alpha 2-autoreceptors by rauwolscine, the electrically evoked tritium overflow was inhibited by various imidazolines and guanidines. The rank order of potency was BDF 7579 (4-chloro-2-isoindolinyl) guanidine) > or = BDF 6143 (4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline) > BDF 6100 [2-(2-imidazolin-2-ylamino)-isoindoline] > clonidine > ST587 (2-(2-chloro-5-trifluoromethylphenylimino) imidazolidine nitrate) > or = cirazoline > tolazoline > idazoxan > phentolamine. Comparison of the potencies of these drugs with those previously found for the presynaptic imidazoline receptors in the rabbit pulmonary artery revealed a very good correlation. In contrast, no positive correlation was found with their affinities for the I1- and I2-imidazoline binding sites in bovine adrenal medullary membranes and with their lipophilicity (log P values). The electrically evoked tritium overflow was also inhibited by the recently identified endogenous imidazoline receptor ligand agmatine, but was not affected by amiloride. In further series of experiments, the ability of putative antagonist at presynaptic imidazoline receptors to counteract the inhibitory effect of imidazoline derivatives was determined. Amiloride, imidazole-4-acetic acid and 1-benzylimidazole did not attenuate the inhibitory effect of BDF 6143 on the electrically evoked tritium overflow. In contrast, rauwolscine antagonized the inhibitory effect of various imidazolines; rauwolscine was clearly less potent in antagonizing the effect of clonidine, BDF 6143 and cirazoline (apparent pA2 6.48-7.32) than in antagonizing that of oxymetazoline and moxonidine (apparent pA2 8.33 and 8.12, respectively). In a final series of experiments, BDF 6143 (under the conditions applied a selective agonist at presynaptic imidazoline receptors) proved to be considerably less potent in inhibiting tritium overflow evoked by high K+ than by electrical stimulation, whereas moxonidine (in rabbit aorta a selective agonist at presynaptic alpha 2-adrenoceptors) exhibited similar potency in inhibiting the overflow evoked by both methods of stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inhibitory presynaptic imidazoline receptors on sympathetic nerves in the rabbit aorta differ from I1- and I2-imidazoline binding sites. 764 14

1. 22Na+ and 36Cl- fluxes across isolated reticular epithelium of sheep were measured by using the Ussing-chamber technique. 2. Net NaCl absorption driven by Na(+)-K(+)-ATPase was observed under short-circuit conditions. 3. Evaluation of fluxes measured under voltage-clamp conditions indicated that Na+ absorption is mainly electroneutral. 4. Mucosal application of bumetanide, hydrochlorothiazide, or low dose amiloride (10(-4) M) produced no changes in Na+ transport whereas addition of higher doses of amiloride (> or = 10(-3) M) led to a reduction in net Na+ transport. Short chain fatty acids (SCFA) enhanced the amiloride-sensitive Na+ transport. 5. Alterations of JmsNa induced by inhibitors or by SCFA were always accompanied by qualitatively similar changes of JsmNa. Amiloride-sensitive JsmNa was also decreased at low mucosal Na+ concentration. 6. DIDS, SITS, and nitrate reduced both JmsCl and JsmCl. SCFA did not influence chloride transport. 7. It is concluded that Na+ transport is mediated by Na(+)-H+ exchange and by transport processes operating as Na+ self-exchange. Mucosal-to-serosal chloride transport seems partly to depend on anion exchange systems.
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PMID:Mechanisms of sodium and chloride transport across isolated sheep reticulum. 809 64

The effect of replacement of chloride by thiocyanate has been investigated in neonatal human red cells. On incubating these cells in isotonic SCN- medium, a rapid cellular swelling was observed, which was not evident in Cl- media. Incubation in hypertonic SCN- medium showed a rapid osmotic shrinkage followed by reswelling back to the initial volume. This regulatory volume increase was completed in a shorter time than in Cl- medium. Whole water accumulated by the cells in both experimental conditions can be accounted for by net Na+ uptake (twofold augmentation with respect to initial value). Amiloride inhibits specifically both cellular swelling and the Na+ content increase in these experimental conditions. Similar experiments in neonatal red cells incubated in NO3- media, as well as in adult red cells placed in NO3- or SCN- media, did not exhibit the same response. The findings suggest that the response of neonatal red cells in a SCN- containing media was mediated by activation of a Na+/H+ antiport mechanism.
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PMID:Foreign anion substitution for chloride in neonatal human red cells. Effect on cellular volume. 857 84

The mechanism(s) of Cl- transport across the human colonic apical membranes are not well understood. Apical membrane vesicles (AMV) purified from organ donor proximal colonic mucosa and a rapid millipore filtration technique were utilized to study 36Cl- uptake into these vesicles. Outwardly directed OH- and HCO3- gradient stimulated 36Cl- uptake into these vesicles demonstrating a transient accumulation over equilibrium uptake. Voltage clamping the membrane potential of the vesicles or making them inside positive with K+/valinomycin failed to influence chloride uptake, indicating that the conductive Cl- uptake pathway is minimal in proximal colonic AMV. Anion exchange inhibitors, DIDS and SITS (1 mM) inhibited OH- and HCO3- stimulated 36Cl- uptake by approximately 60%. Furosemide also demonstrated a small but significant inhibition of chloride uptake. Amiloride, bumetanide and acetazolamide (1 mM) failed to inhibit 36Cl uptake. HCO3- and pH gradient stimulated 36Cl- uptake exhibited saturation kinetics with an apparent Km for chloride of 4.0 +/- 0.7 mM and Vmax of 17.8 +/- 3.9 nmol/mg per min. Bromide, chloride, nitrate and acetate (50 mM each) inhibited 5 mM 36Cl uptake. Inwardly directed gradients of Na+, K+, or Na+ and K+ did not stimulate 36Cl- uptake into these vesicles, indicating that uptake of Na+ and Cl- in human proximal colonic AMV does not involve Na-Cl or Na-K-2Cl cotransport. The above findings indicate that chloride transport in human proximal colonic AMV involves an electroneutral Cl-HCO3- (OH-) exchange process. In view of the previous demonstration of Na+-H+ antiporter in these vesicles, dual ion exchange mechanism of Na+-H+ and Cl-HCO3- in apical membrane domain of human colonocytes is postulated to be the primary mechanism for NaCl absorption in the human proximal colon.
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PMID:Chloride transport in human proximal colonic apical membrane vesicles. 863 5


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