Sodium chloride regulation of the α epithelial amiloride-sensitive sodium channel (αENaC) gene requires syntheses of new protein(s)
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Epithelial sodium channel
Amiloride
Hypertonic saline
Pathophysiological features of both primary aldosteronism and pseudohyperaldosteronism are hyperactive amiloride-sensitive epithelial Na + channels (ENaC) and refractory hypertension. Peripheral blood lymphocytes express ENaC, which functions and is regulated similarly to ENaC expressed by renal principal cells. Thus it was hypothesized that individuals with either of these hypertensive etiologies could be identified by assessment of the function and regulation of peripheral blood lymphocyte ENaC, by whole cell patch clamp. We also tested the hypothesis that specific inhibition of hyperactive ENaC with amiloride could ameliorate the hypertension. To test these hypotheses, we solicited blood samples from normotensive, controlled hypertensive, and refractory hypertensive individuals. Lymphocytes were examined electrophysiologically to determine whether ENaC was hyperactive. All positive findings were from refractory hypertensive individuals. Nine refractory hypertensive patients had amiloride added to their hypertensive therapy. Amiloride normalized the blood pressure of four subjects. These individuals all had hyperactive ENaC. Amiloride had no effect on individuals with normal ENaC. These findings suggest that whole-cell patch clamp of peripheral blood lymphocytes can be used to identify accurately and rapidly hypertensive individuals who will respond to amiloride therapy.
Epithelial sodium channel
Amiloride
Refractory (planetary science)
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Epithelial sodium channel
Amiloride
Apical membrane
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Lungs from near-term fetal guinea pigs (62 ± 2 days of gestation) were supported in vitro for 3 h; lung-liquid production was monitored by a dye-dilution method based on Blue Dextran 2000. Untreated preparations produced fluid at 1.26 ± 0.14 mL∙kg −1 body mass∙h −1 , with no significant change over the ensuing hours (ANOVA, regression analysis; n = 16). Experimental preparations received aldosterone at plasma concentrations reported to be present at birth. Aldosterone produced rapid, significant reductions in fluid production, and occasionally reabsorptions, which persisted beyond treatment. Reductions during treatment were as follows: 10 −8 M aldosterone, 90.8 ± 4.9% (P < 0.001; n = 4); 2 × 10 −9 M aldosterone, 64.1 ± 16.6% (P < 0.05–0.001; n = 6), and 7 × 10 −10 M aldosterone, 48.6 ± 11.7% (P < 0.005–0.001; n = 6). The linear log dose response curve (r = 0.99) showed a theoretical threshold at 3.4 × 10 −11 M aldosterone. Responses to 7 × 10 −10 M aldosterone were abolished by 10 −6 M amiloride. At the highest concentration of aldosterone (10 −8 M), 10 −6 M amiloride significantly reduced responses, and the changes were no longer significant by ANOVA. At both high and low aldosterone concentrations, responses with amiloride were significantly lower than those without amiloride (ANOVA, P < 0.03–0.04). Amiloride controls and untreated preparations showed no significant changes in fluid production. It is concluded that aldosterone at plasma concentrations present at birth can cause reductions in lung-liquid production or reabsorption through effects on amiloride-sensitive Na + channels, and that the responses are remarkably rapid.
Amiloride
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Epithelial sodium channel
Amiloride
Acid-sensing ion channel
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Amiloride
Epithelial sodium channel
Acid-sensing ion channel
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Epithelial sodium channel
Amiloride
Alveolar Epithelium
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Renal excretion and sodium appetite provide the basis for sodium homeostasis. In both the kidney and tongue, the epithelial sodium channel (ENaC) is involved in sodium uptake and sensing. The diuretic drug amiloride is known to block ENaC, producing a mild natriuresis. However, amiloride is further reported to induce salt appetite in rodents after prolonged exposure as well as bitter taste impressions in humans. To examine how dietary sodium content and amiloride impact on sodium appetite, mice were subjected to dietary salt and amiloride intervention and subsequently analyzed for ENaC expression and taste reactivity. We observed substantial changes of ENaC expression in the colon and kidney confirming the role of these tissues for sodium homeostasis, whereas effects on lingual ENaC expression and taste preferences were negligible. In comparison, prolonged exposure to amiloride-containing drinking water affected β- and αENaC expression in fungiform and posterior taste papillae, respectively, next to changes in salt taste. However, amiloride did not only change salt taste sensation but also perception of sucrose, glutamate, and citric acid, which might be explained by the fact that amiloride itself activates bitter taste receptors in mice. Accordingly, exposure to amiloride generally affects taste impression and should be evaluated with care.
Epithelial sodium channel
Amiloride
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Epithelial sodium channel
SGK1
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Epithelial sodium channel
Amiloride
Apical membrane
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Amiloride-sensitive sodium channels in the lung play an important role in lung fluid balance. Particularly in the alveoli, sodium transport is closely regulated to maintain an appropriate fluid layer on the surface of the alveoli. Alveolar type II cells appear to play an important role in this sodium transport, with the role of alveolar type I cells being less clear. In alveolar type II cells, there are a variety of different amiloride-sensitive, sodium-permeable channels. This significant diversity appears to play a role in both normal lung physiology and in pathological states. In many epithelial tissues, amiloride-sensitive epithelial sodium channels (ENaC) are formed from three subunit proteins, designated α-, β-, and γ-ENaC. At least part of the diversity of sodium-permeable channels in lung arises from the assembling of different combinations of these subunits to form channels with different biophysical properties and different mechanisms for regulation. This leads to epithelial tissue in the lung, which has enormous flexibility to alter the magnitude and regulation of salt and water transport. In this review, we discuss the biophysical properties and occurrence of these various channels and some of the mechanisms for their regulation.
Epithelial sodium channel
Amiloride
Alveolar Epithelium
Pulmonary alveolus
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