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At least 19 recordsLinked to original sources

PubMed1992

Amiloride antagonizes beta-adrenergic stimulation of cAMP synthesis and Cl- secretion in human tracheal epithelial cells.

Amiloride, a potent blocker of the sodium channel in airway epithelium, has been administered by aerosol as a therapeutic agent for cystic fibrosis. Because amiloride in high concentration has been reported to interfere with cell functions, including adrenergic responses, we tested the ability of amiloride to inhibit beta-adrenergic responses in human tracheal epithelial cells. Amiloride (10(-4) M), applied from the basolateral surface of a cell monolayer, inhibited the changes in transepithelial potential and short circuit current to isoproterenol (10(-6) M). The stimulation of cyclic adenosine monophosphate (cAMP) synthesis by isoproterenol was inhibited in dose-dependent fashion by amiloride (P = 0.007 by multivariate ANOVA with multiple samples correction). Amiloride did not affect baseline transepithelial potential, short circuit current, basal cAMP levels, cAMP response to prostaglandin E2, or basal adenylate cyclase activity measured directly in membrane preparations. Therefore, it is unlikely that amiloride exerts a nonspecific toxic effect on adenylate cyclase, receptor-cyclase coupling, or substrate or cofactor supply. The binding of [125I]iodocyanopindolol (ICYP), a beta-adrenergic receptor antagonist, to membranes from human tracheal epithelial cells could be displaced by amiloride with IC50 = 410 microM; displacement was 70% at 10(-3) M amiloride. These data are most consistent with the hypothesis that amiloride inhibits beta-adrenergic responses in airway epithelial cells by occupying beta-adrenergic receptor sites. Therapeutic administration of amiloride should take into account its affinity for adrenergic receptors.

Adenylyl Cyclases↗

PubMed1979

Interaction of amiloride and lithium on distal urinary acidification.

The interaction of amiloride and LiCl administration on renal HCO3 handling was studied in hydropenic rats. Amiloride administration resulted in a significant increase in Na, Cl, and HCO3 excretion, whereas K excretion decreased significantly. LiCl administration resulted in a significant increase in Na, Cl, K, and HCO3 excretion. LiCl administration to animals receiving amiloride led to a significant increase in HCO3 excretion but failed to cause an increase in Na or K excretion. Addition of amiloride to animals receiving LiCl resulted in a significant increase in Na and HCO3 excretion. The net increase in fractional HCO3 excretion seen in this group was greater than that seen in all other groups. The finding that the net increase in FEHCO3 was greater in animals receiving amiloride after administration of LiCl than in animals receiving LiCl after amiloride administration indicates that amiloride blunted the effect of LiCl on HCO3 excretion. Administration of amiloride to both normal rats and to rats infused with Li during HCO3 administration resulted in a significant decrease in U-B Pco2 which could not be explained by the decrease in urine HCO3 concentration. These data demonstrate that amiloride inhibits distal acidification in vivo. LiCl administration also resulted in a decrease in U-B Pco2 which could be explained by the decrease in urine HCO3 concentration. LiCl administration also resulted in a decrease in TcH2O which could be prevented by prior administration of amiloride. These data indicate that amiloride blunts the effect of LiCl on urinary acidification, an effect similar to that observed on urinary concentration. These data suggest that the effect of Li on urinary acidification is in part dependent on Li entry into the cell.

Amiloride↗

PubMed1977

Mode of action of amiloride in toad urinary bladder. An electrophysiological study of the drug action on sodium permeability of the mucosal border.

The effect of amiloride on the sensitivity to Na of the mucosal border of toad urinary bladder was investigated by recording Na concentration-dependent transepithelial potential difference (Vt) and the intracellular potential. When mucosal Na concentration was normal, amiloride added to the mucosal solution at 10(-4) M markedly reduced the mucosal membrane potential (Vm) and altered the potential profile from a two-step type to a well type. Similar changes were observed when Na was totally eliminated from the mucosal medium. The serosal membrane potential was insensitive to amiloride and elimination of mucosal Na. In the absence of amiloride, the Vt could be described by the Goldman-Hodgkin-Katz equation in the range of mucosal Na concentration from 0 to 16 mM, and amiloride extended this concentration range. By using the Goldman-Hodgkin-Katz equation. Na permeability was calculated from the data of Vt's obtained in the allowed ranges of Na concentration and compared before and after the addition of amiloride. The results show that Na permeability decreases to 1/600 of control when the maximum dose of amiloride (10(-4) M) is applied. The relationship between Na permeability and amiloride concentration is well explained on the basis of assumptions that amiloride binds to the Na site of the mucosal border in one-to-one fashion and in a competitive manner with Na and that Na permeability reduces in proportion to increase in number of the sites bound with amiloride.

Amiloride↗

PubMed1992

The mode of interaction of amiloride and some of its analogues with the adenosine A1 receptor.

Amiloride, a potassium sparing diuretic, inhibits adenosine A1 receptor-radioligand binding in calf and rat brain membranes in the low micromolar range. The drug interacted with the A1 receptor in a manner different from classical A1 ligands, but structure-activity relationship studies indicated that this inhibitory effect is not related to the ion transport inhibiting properties of amiloride (Garritsen et al., 1990a,b) In the present study, the question is addressed how amiloride interacts with the adenosine A1 receptor. Amiloride and two of its analogues, in concentrations equivalent to their Ki values in displacement studies, decrease the affinity of the A1 antagonist [3H]8-cyclopentyl-1,3-dipropylxanthine, but not the maximal binding capacity of the radioligand. Furthermore, the dissociation rate of the receptor-ligand complex is unaltered in the presence of amiloride or its analogues in a concentration exceeding the Ki value 10-fold. These characteristics argue for a purely competitive mode of interaction. The functional consequences of the interaction between amiloride analogues and the A1 receptor were investigated at the level of cyclic adenosine 3',5'-monophosphate (cAMP) formation. The amiloride analogue 5-(N-butyl-N-methyl) amiloride (MBA) reversed A1-receptor mediated inhibition of forskolin-stimulated cAMP formation in rat fat cell membranes. In this model, the antagonist potency of MBA is ca 5 microM. This value is in fair agreement with a Ki value of 3.5 microM in binding assays under similar conditions. In conclusion, amiloride inhibits A1 receptor binding in an apparently competitive manner. This suggests that the binding sites of amiloride and the classic A1 receptor ligands may at least partially overlap.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

PubMed1992

Amiloride inhibits the growth of human colon cancer cells in vitro.

Cytoplasmic alkalinization induced by activation of the Na+/H+ antiport plays an essential role in the initiation of cell proliferation. In the present study we examined the effects of amiloride, a specific and reversible inhibitor of Na+/H+ antiporter, on the growth of human colon cancer cells (HT-29). Amiloride (50-800 microM) inhibited the growth of HT-29 cells in a dose-dependent fashion. Forty-three percent inhibition of growth was found at an amiloride concentration of 400 microM after 4 days of treatment. The inhibitory effect of amiloride on growth of HT-29 cells was reversible since removal of amiloride by a media change after 48 h treatment lead to rapid regrowth to control levels. The reversibility of growth inhibition suggests that amiloride is not a non-specific cytotoxin for HT-29 cells. We examined the possible mechanisms for the inhibitory effects of amiloride. Amiloride (400 microM) completely abolished serum-stimulated ODC activity and inhibited difluoromethylornithine (DMFO)-stimulated putrescine uptake by 56%. We conclude that amiloride inhibits the in vitro growth of human colon cancer cells; since ODC-activity and polyamine transport were both inhibited, the inhibitory effects may be mediated in part by polyamine-dependent processes. Amiloride may be a useful agent in the treatment of colon cancer.

Adenocarcinoma↗

PubMed1979

Effect of amiloride on the apical cell membrane cation channels of a sodium-absorbing, potassium-secreting renal epithelium.

The effect of the K-sparing diuretic amiloride was assessed electrophysiologically in the isolated cortical collecting tubule of the rabbit, a segment which absorbs Na and secretes K. Low concentrations of amiloride in the perfusate caused a rapid, reversible, decrease in the magnitude of the lumen negative transepithelial potential difference, Vte, transepithelial conductance Gte, and equivalent short-circuit current, Isc, with an apparent K1/2 of approximately 7 X 10(-8) M. The effects of a maximum inhibitory concentration of amiloride (10(-5) M) were identical to those observed upon Na removal from lumen and bath (Na removal from the bath alone has no effect). Removal of Na in the presence of 10(-5) M amiloride had no affect on Vte, Gte, or Isc, and is consistent with the view that amiloride blocks the Na conductive pathways of the apical cell membrane. Further, in the absence of Na, the subsequent addition of amiloride had no influence. In tubules where active Na absorption was either spontaneously low, or abolished by removal of Na from lumen and bath, the elevation of K from 5 to 155 meq/liter in the perfusate caused a marked change of the Vte in the negative direction and an increase in the Gte. These effects could be attributed to a high K permeability of the apical cell membrane and not of the tight junctions. Amiloride (10(-5) M) had no effect on these responses to K. It is concluded that amiloride selectively blocks the apical cell membrane Na channels but has no effect on the K conductive pathway(s). This selective nature of amiloride may indicate that Na and K are transported across the apical cell membrane via separate conductive pathways.

Absorption↗

PubMed1992

Millimolar amiloride concentrations block K conductance in proximal tubular cells.

1. Amiloride, applied at millimolar concentrations, results in the blockade of K+ conductance in amphibian proximal convoluted cells (PCT), fused into giant cells. 2. Amiloride results directly in a blockade of K+ conductance that is not related to inhibition of the Na(+)-H+ antiport, which would lower intracellular pH, adversely affecting K+ conductance. On the contrary, high amiloride concentrations promote entry of this lipophilic base in the cell, leading to higher cell pH. 3. Under voltage clamp conditions, control vs. amiloride, current-voltage curves from PCT fused giant cells intersect at -86.2 +/- 3.4 mV, a value close to the equilibrium potential for potassium. 4. Hexamethylene amiloride, 10(-5) M, irreversibly depolarizes the membrane potential. 5. Barium decreased by 50% the initial slope of realkalinization, following removal of a solution containing NH4Cl, as did amiloride. In addition, these blockers reduced membrane conductance by 40%, suggesting that a fraction of the amiloride-suppressible NH4+ efflux may be conductive. 6. Amiloride does not directly inhibit the Na(+)-K+, ATPase in our preparation, contrary to the prevalent belief. 7. In vivo studies show that amiloride interferes with an apical K+ conductance but it does not alter basolateral K+ conductance.

Amiloride↗

PubMed1978

Effect of amiloride on the renal response to saline expansion in new-born dogs.

1. The renal effects of amiloride were studied in twenty-six new-born and nine adult dogs, with and without saline expansion. 2. Without saline expansion, amiloride inhibited more sodium reabsorption (normalized to GFR) in puppies than in adults (5.95 vs. 2.18 muequiv/ml. GFR, P less than 0.01). Amiloride inhibited sodium reabsorption more in saline expanded than in nonexpanded puppies (9.39 vs. 5.95 muequiv/ml. GFR, P less than 0.01) but there was no difference between expanded and non-expanded adults. 3. Saline expansion by itself increased fractional sodium excretion (CNa/GFR) more in the adult than in the puppy (0.071 vs. 0.019, P less than 0.01). During amiloride inhibition, saline expansion increased CNa/GFR to 0.045 in the puppy (compared to 0.019 in the nonamiloride inhibited puppy) but saline expansion increased CNa/GFR to the same degree in the amiloride as in the non-amiloride inhibited adult. 4. In all puppies amiloride inhibited more sodium reabsorption than potassium secretion and there was poor correlation between the degree of inhibition of sodium reabsorption and potassium secretion for both the puppy (r = 0.14) and the adult (r = 0.05). 5. Assuming that amiloride acts by inhibiting sodium reabsorption and potassium secretion in the late distal and cortical collecting tubules, these results support the conclusion that in these regions of the nephron of the new-born dog (a) a greater fraction of the filtered sodium is reabsorbed than in the adult and (b) increased fractional sodium reabsorption is responsible, in part, for the attenuated natriuretic response to saline expansion.

Absorption↗

PubMed1976

Non-specific inhibition of membrane-ATPase by amiloride: a comparative in vivo and in vitro study with ouabain.

The submaxillary duct epithelium, which actively transports Na+ (rabbit) and, in addition, K+ and H+/HCO-/3 (rat), was used as a model epithelium to compare the effects of ouabain and amiloride on transport parameters. 1. Ouabain was only effective from the interstitial side, amiloride, however, only from the luminal side. Amiloride induced effects on transport of the ions were seen within less than 1 s, ouabain effects, however, only after minutes. 2. Ouabain inhibited in a parallel fashion the Na+ transport potential and the Na+-K+-ATPase activity. It had no effect on the Mg2+-ATPase and the HCO-/3-ATPase. 3. Amiloride also inhibited the Na+ transport potential and the Na+-K+-ATPase; however, the Na+ transport potential was significantly more sensitive to amiloride than the Na+-K+-ATPase. 4. Amiloride inhibited in a similar fashion the Na+-K+-ATPase, the Mg2+-ATPase and the HCO-/3-ATPase, but did not influence active HCO-/3 secretion. 5. It is concluded that the amiloride induced effects on the membrane ATPases are non-specific.

4-Nitrophenylphosphatase↗

PubMed1992

Invertebrate epithelial Na+ channels: amiloride-induced current-noise in crab gill.

Epithelial sheets (including cuticle) from posterior gills of the freshwater-adapted euryhaline crab Eriocheir sinensis were obtained according to the method of Schwarz and Graszynski ((1989) Comp. Biochem. Physiol. 92A, 601-604; (1989) Verh. Dtsch. Zool. Ges. 82, 211 and (1989) Arch. Int. Physiol. Biochim. 97, C45). With external NaCl-saline, the outward-directed short-circuit current (Isc) could hardly be influenced by external amiloride up to 100 mumol/l but was, on the contrary, strictly dependent on apical Cl- (Onken, Graszynski and Zeiske (1991) J. Comp. Physiol. B 161, 293-301). In absence of external chloride an inward-directed, amiloride-inhibitable Isc was observed which depended on external Na+ (thus, Isc approximately INa) in a two-step, saturating mode. The Isc-block by amiloride obeyed saturation kinetics (half-maximal at less than or equal to 1 mumol/l, suggesting apical Na(+)-channels). Only for Na+ concentrations below 100 mmol/l we found an indication for a competitive interaction between Na+ and amiloride at the channel. Current fluctuation analysis revealed the presence of an amiloride-induced relaxation (Lorentzian) component in the Isc-noise (so-called 'blocker-noise'). The Lorentzian parameter-shifts with increasing amiloride concentration indicate first-order kinetics of the blocker with its apical receptor. Using a 'two-state' blocking model we calculated, for amiloride concentrations between 2 and 5 mumol/l, a mean single-channel current of 0.46 pA and a mean channel density of 250.10(6) cm-2.

Amiloride↗

PubMed1979

On the mechanism of the amiloride-sodium entry site interaction in anuran skin epithelia.

The steady-state transport kinetics of the interaction between external sodium and the diuretic drug, amiloride, was studied in isolated anuran skin epithelia. We also investigated the effect of calcium on the amiloride-induced inhibition of short-circuit current (Isc) in these epithelial preparations. The major conclusions of this study are: (a) amiloride is a noncompetitive inhibitor of Na entry in bullfrog and grassfrog skin, but displays mixed inhibition in R. temporaria and the toad. A hypothesis which states that the interaction sites for amiloride and Na on the putative entry protein are spatially distinct in all of these species is proposed. (b) The stoichiometry of interaction between amiloride and the Na entry mechanism is not necessarily one-to-one. (c) The external Ca requirement for the inhibitory effect of amiloride is not absolute. Amiloride, at all concentrations, is equally effective in inhibiting Isc of bullfrog skin independently from the presence or absence of external Ca.

Amiloride↗

PubMed1979

The effects of amiloride and ouabain on urinary acidification by turtle bladder.

To investigate the mechanism by which amiloride inhibits urinary acidification, its effects on H+ secretion were examined in the isolated urinary bladder of the fresh water turtle. In short-circuited turtle bladders amiloride inhibited H+ secretion by 30% and Na+ transport by 100%. Maximal inhibition was reached at 10(-4) M amiloride for both transport systems. In contrast to amiloride, ouabain did not affect H+ secretion despite complete inhibition of Na+ transport. In bladders first treated with ouabain amiloride failed to inhibit H+ secretion and in bladders first treated with amiloride, the inhibition of H+ secretion was partially reversed by ouabain. The inhibition of H+ secretion by amiloride is attributed to hyperpolarization of the luminal cell membrane and the imposition of a voltage opposing the movement of protons in the active transport pathway.

Acid-Base Equilibrium↗

PubMed1975

Comparison of the local effects of amiloride hydrochloride on the isotonic fluid absorption in the distal and proximal convoluted tubule.

The isotonic fluid absorption (Jv) was measured under standard conditions in the proximal and distal convolution of the rat kidney. The peritubular blood capillaries were perfused simultaneously. Amiloride was applied either intraluminally or peritubularly. When applied intraluminally, amiloride strongly inhibited Jv in the distal tubule at concentrations up to 10(-6) M. In the proximal tubule similar effects were obtained only after intraluminal application of one thousand-fold greater concentrations of amiloride. In contrast to amphibian epithelia, amiloride also inhibits Jv in the distal tubule when applied peritubularly, but at higher concentrations and less completely than after intraluminal application. Amiloride was found to be generally more effective in the distal tubule than furosemide and mefruside, although in the proximal tubule it was less effective than these diuretics. That amiloride is most effective after intraluminal application in the distal tubule would suggest a dominant action at the luminal membrane of the distal tubule cell, while not excluding a concomitant effect at the peritubular membrane.

Absorption↗

PubMed1978

Effect of amiloride on catecholamine-induced changes in ion transport in short-circuited frog skin.

The effect of amiloride (10(-6) M), added either before or after the catecholamine, on the adrenaline- or isoprenaline-induced changes in short-circuit current and Na and Cl fluxes of isolated skin of Rana temporaria was investigated. At the catecholamine concentration used the increment in short-circuit was the same in the absence or presence of amiloride (ca. 7.1 neq.cm-2.min-1) and the amiloride inhibition was the same in the absence or presence of catecholamine (ca. 9.4 neq.cm-2.min-1). Amiloride inhibited the Na and Cl influxes of the control period (by --8.63 +/- 1.28 and --2.08 +/- 0.75 neq.cm-2.min-1, respectively) but did not prevent the increase of these fluxes on the addition of adrenaline. There was no evidence of amiloride inhibition of the Na and Cl effluxes. There was an association between the increase of Na efflux and net Cl efflux following adrenaline, which if secreted together by a neutral NaCl pump would not contribute to the increased short-circuit current. The increased short-circuit current was correlated with the increased Na influx throughout the experiment if allowance is made for the periods where there is a lag between the current and isotopic measurement (i.e., the period immediately after the addition of a drug). It is tentatively suggested that the catecholamine-induced increase in Na influx is not altered by the amiloride concentration used in this study. In addition the magnitude of the changes induced by catecholamine in the influx and efflux of both Na and Cl seem to be unaffected.

Amiloride↗

PubMed1992

Amiloride in ouabain-induced acidification, inotropy and arrhythmia: 23Na & 31P NMR in perfused hearts.

The increase in intracellular sodium (Nai), resulting from inhibition of the Na/K ATPase by cardiac glycosides, is known to increase calcium influx via Na(+)-Ca2+ exchange, and thereby increase contractility. This increase in intracellular Ca2+ has been related to the development of intracellular acidification and enhanced activity of the Na(+)-H+ exchanger as a measure by the cell to prevent further acidification. Thus, the efflux of the H+ ions results in an additional increase in Nai. This may subsequently lead to an increased rate of Ca2+ influx and therefore to the potentiation of the effects of cardiac glycosides. To assess the role of Na(+)-H+ exchange in the mechanism of ouabain action in the beating heart we used amiloride, a known inhibitor of Na(+)-H+ exchange. Isolated rat hearts were perfused with either ouabain (50 microM) alone (n = 8, Group I), amiloride (1.0 mM) + ouabain (50 microM) (n = 8, Group II), or amiloride (1.0 mM) alone as a control group (n = 4, Group III). 23Na and 31P NMR spectroscopy were used to assess the changes in Nai and intracellular pH (pHi), respectively, while simultaneous and continuous monitoring of left ventricular pressure was carried out. Perfusion with both ouabain alone (Group I) or ouabain + amiloride (Group II), resulted in a time dependent increase in Nai levels, reaching (within 25 mins) a maximum of 200 +/- 7% of control in Group I, and 170 +/- 10% of control in Group II. Concurrently, a mild but significant decrease in pHi was observed in both groups. This decrease, however, was significantly higher in Group II compared to Group I (0.34 pH units vs. 0.19 pH units, respectively; P less than 0.05), suggesting that inhibition of Na(+)-H+ exchange by amiloride limits the recovery from ouabain-induced intracellular acidification. While developed pressure gradually increased in Group I to a maximum of 268 +/- 52% of control, the addition of amiloride in Group II substantially reduced the positive inotropic effect. Ventricular fibrillation (VF) developed in three of the eight hearts in Group I within 10-13 mins after the addition of ouabain. Interestingly, the rate of Nai increase in hearts that sustained VF was significantly higher compared to those without VF (mean slope 10.1 +/- 2.11 vs. 3.9 +/- 1.0, respectively; P less than 0.0001). Ventricular fibrillation did not develop in Group II or III.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride↗

PubMed1992

Primary structure of an apical protein from Xenopus laevis that participates in amiloride-sensitive sodium channel activity.

High resistance epithelia express on their apical side an amiloride-sensitive sodium channel that controls sodium reabsorption. A cDNA was found to encode a 1,420-amino acid long polypeptide with no signal sequence, a putative transmembrane segment, and three predicted amphipathic alpha helices. A corresponding 5.2-kb mRNA was detected in Xenopus laevis kidney, intestine, and oocytes, with weak expression in stomach and eyes. An antibody directed against a fusion protein containing a COOH-terminus segment of the protein and an antiidiotypic antibody known to recognize the amiloride binding site of the epithelial sodium channel (Kleyman, T. R., J.-P. Kraehenbuhl, and S. A. Ernst. 1991. J. Biol. Chem. 266:3907-3915) immunoprecipitated a similar protein complex from [35S]methionine-labeled and from apically radioiodinated Xenopus laevis kidney-derived A6 cells. A single integral of 130-kD protein was recovered from samples reduced with DTT. The antibody also cross-reacted by ELISA with the putative amiloride-sensitive sodium channel isolated from A6 cells (Benos, D. J., G. Saccomani, and S. Sariban-Sohraby. 1987. J. Biol. Chem. 262:10613-10618). Although the protein is translated, cRNA injected into oocytes did not reconstitute amiloride-sensitive sodium transport, while antisense RNA or antisense oligodeoxynucleotides specific for two distinct sequences of the cloned cDNA inhibited amiloride-sensitive sodium current induced by injection of A6 cell mRNA. We propose that the cDNA encodes an apical plasma membrane protein that plays a role in the functional expression of the amiloride-sensitive epithelial sodium channel. It may represent a subunit of the Xenopus laevis sodium channel or a regulatory protein essential for sodium channel function.

Amiloride↗

PubMed1992

Proton currents through amiloride-sensitive Na channels in hamster taste cells. Role in acid transduction.

The activity of taste cells maintained in the intact hamster tongue was monitored in response to acid stimulation by recording action currents from taste receptor cells with an extracellular "macro" patch pipette: a glass pipette was pressed over the taste pore of fungiform papillae and perfused with citric acid, hydrochloric acid, or NaCl. Because this technique restricted stimulus application to the small surface area of the apical membranes of the taste cells, many nonspecific, and potentially detrimental, effects of acid stimulation could be avoided. Acid stimulation reliably elicited fast transient currents (action currents of average amplitude, 9 pA) which were consistently smaller than those elicited by NaCl (29 pA). The frequency of action currents elicited by acid stimuli increased in a dose-dependent manner with decreasing pH from a threshold of about pH 5.0. Acid-elicited responses were independent of K+, Na+, Cl-, or Ca2+ at physiological (salivary) concentrations, and were unaffected by anthracene-9-carboxylic acid, tetraethylammonium bromide, diisothiocyanate-stilbene-2,2'-disulfonic acid, vanadate, or Cd2+. In contrast, amiloride (< or = 30 microM) fully and reversibly suppressed acid-evoked action currents. At submaximal amiloride concentrations, the frequency and amplitude of the action currents were reduced, indicating a reduction of the taste cell apical conductance concomitant with a decrease in cell excitation. Exposure to low pH elicited, in addition to transient currents, an amiloride-sensitive sustained d.c. current. This current is apparently carried by protons instead of Na+ through amiloride-sensitive channels. When citric acid was applied while the taste bud was stimulated by NaCl, the action currents became smaller and the response resembled that produced by acid alone. Because of the strong interdependence of the acid and salt (NaCl) responses when both stimuli are applied simultaneously, and because of the similarity in the concentration dependence of amiloride block, we conclude that amiloride-sensitive Na+ channels on hamster taste receptor cells are permeable to protons and may play a role in acid (sour) taste.

Action Potentials↗

PubMed1992

Inhibition by amiloride of ouabain-evoked catecholamine secretion from cultured adrenal chromaffin cells: evidence for its blocking action on interaction between ouabain and Na+/K(+)-pump.

The effect of amiloride on ouabain-evoked catecholamine secretion was investigated in primary cultures of bovine adrenal chromaffin cells. Catecholamine secretion evoked by ouabain was inhibited markedly by amiloride, but the secretion evoked by Na+ removal was not affected by the drug. In contrast, adriamycin, a putative inhibitor of the Na(+)-Ca++ exchange, inhibited the secretion evoked by Na+ removal as well as that evoked by ouabain. The inhibitory action of amiloride on the ouabain-evoked secretion was therefore considered to be due to its action on other mechanism(s) than the Na(+)-Ca++ exchange process. Further studies showed that the uptake of 86Rb+ into the cells was slightly but significantly reduced by amiloride, and the inhibitory action of ouabain on 86Rb+ uptake was considerably blocked by this drug under the experimental conditions in which the inhibition of ouabain-evoked secretion was observed. The binding of [3H] ouabain to the intact cells was also inhibited by amiloride under the same conditions. These results suggest that amiloride may inhibit ouabain-evoked catecholamine secretion as a consequence of blocking the inhibitory action of ouabain on the plasma membrane Na+/K(+)-pump in adrenal chromaffin cells.

Adrenal Medulla↗