更新于：2024-11-01

ENaCα

更新于：2024-11-01

基本信息

别名

Alpha-ENaC、Alpha-ENaC","ENaCA、Alpha-NaCH

+ [10]

简介

Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and eccrine sweat glands. Also plays a role in taste perception.

关联

项与 ENaCα 相关的药物

Amiloride Hydrochloride

盐酸阿米洛利

靶点

ENaCα

作用机制

ENaCα抑制剂

在研机构

Padagis US LLC

原研机构

Perrigo Co. Plc

在研适应症

心脏衰竭 [+1]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期1981-10-05

ARO-ENaC

靶点

ENaCα x αvβ6

作用机制

ENaCα抑制剂 [+2]

在研机构

Arrowhead Pharmaceuticals, Inc.

原研机构

Arrowhead Pharmaceuticals, Inc.

在研适应症

囊性纤维化

非在研适应症

肺囊性纤维化

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

ANT-701

靶点

ENaCα

作用机制

ENaCα抑制剂

在研机构

AeroNeph Therapeutics

原研机构

AeroNeph Therapeutics

在研适应症

囊性纤维化 [+1]

非在研适应症-

最高研发阶段临床阶段不明

首次获批国家/地区-

首次获批日期1800-01-20

项与 ENaCα 相关的临床试验

NCT05753059 / Recruiting临床1期IIT

Mechanisms of Diuretic Resistance in Heart Failure, Aim 2

Randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations placebo/placebo, bendroflumethiazide/placebo, amiloride/placebo, and bendroflumethiazide/amiloride added to bumetanide.

开始日期2023-08-10

申办/合作机构

Yale University

[+1]

NCT05125237 / Active, not recruitingN/AIIT

Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines (DREAM)- Amiloride vs Triamterene

This study aims to evaluate the comparative risk of dementia/Alzheimer's disease onset between patients treated with medications that target specific metabolic pathways and patients treated with alternative medications for the same indication.

开始日期2021-10-01

申办/合作机构

The Brigham & Women's Hospital, Inc.

[+3]

NCT04331691 / Completed临床4期IIT

SPironolactone Versus Amiloride for Treatment of REsistant Hypertension (SPARE Trial): A Comparison of Home Blood Pressure

Resistant hypertension is defined as blood pressure that remains above goal despite concurrent use of three antihypertensive agents of different classes including diuretics. Patients with resistant hypertension has at least 1.5-fold higher cardiovascular risk than those with non-resistant hypertension. Therefore, controlling blood pressure is crucial in patients with resistant hypertension.
It has been unclear which antihypertensive agent should be added in patients who cannot reach target blood pressure despite use of three antihypertensive agents. There have been three randomized clinical trials that proved the efficacy of spironolactone in resistant hypertension, but they were small sized, comparison study to placebo. Recently published PATHWAY-2 study which compared the efficacy of spironolactone with placebo, doxazosin, and bisoprolol showed superiority of spironolactone in blood pressure lowering in patients with resistant hypertension. Thus, revised ACC/AHA and ESC/ESH guideline for arterial hypertension recommended spironolactone as the fourth agent for resistant hypertension. However, in real world, adherence to spironolactone may not be adequate because of adverse effect such as gynecomastia, hyperkalemia, and so on.
Recently, sub-study of PATHWAY-2 revealed that amiloride changes systolic blood pressure by -22.2 mmHg (95% CI, -24.7 to -19.7) which is comparable with the effect of spironolactone (-21.8 mmHg; 95% CI, -24.2 to -19.3). However, it was not randomized clinical trial to compare the effect between spironolactone and amiloride in patients with resistant hypertension.
This study aims to compare the effect of spironolactone and amiloride on home blood pressure in resistant hypertensive patients and to compare the rate of target blood pressure achievement between spironolactone and amiloride in resistant hypertensive patients.

开始日期2020-11-16

申办/合作机构

Yonsei University

100 项与 ENaCα 相关的临床结果

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100 项与 ENaCα 相关的转化医学

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0 项与 ENaCα 相关的专利（医药）

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745

项与 ENaCα 相关的文献（医药）

2024-10-01·Journal of the American Society of Nephrology

Potassium-Alkali–Enriched Diet, Hypertension, and Proteinuria following Uninephrectomy

Article

作者: Pastor-Soler, Nuria M ; McFarlin, Brandon E ; McDonough, Alicia A ; Priver, Taylor S ; Schwindt, Seth ; Lei, Hillmin ; Ha, Darren ; Ralph, Donna L ; Smith, Scotti D ; Koepsell, Hermann ; Pandya, Drishti ; Edwards, Aurelie

Key Points

A K-alkali–enriched diet blunted post-uninephrectomy hypertension and facilitated acid clearance by suppressing Na+ reabsorption.

Uninephrectomy-associated proteinuria could be attributed to elevated single-nephron GFR and downregulation of megalin, which reduced fractional protein endocytosis.

BackgroundLosing or donating a kidney is associated with risks of developing hypertension and albuminuria. Few studies address mechanisms or interventions. We investigate the potential benefits of a K+- alkali–enriched diet and the mechanisms underlying proteinuria.MethodsMale Sprague Dawley rats were fed either a 2% NaCl+0.95% KCl diet (HNa-LK) or a 0.74% NaCl+3% K+-alkali diet (HK-alk) for 3 weeks before uninephrectomy and then maintained on respective diets for 12 weeks. BP (by tail-cuff), urine, blood, and kidney proteins were analyzed before and after uninephrectomy.ResultsBefore uninephrectomy, HK-alk–fed versus HNa-LK–fed rats exhibited similar BPs and plasma [K+], [Na+], but lower proximal (NHE3, sodium bicarbonate cotransporter 1, NaPi2) and higher distal (NCC, ENaC, and pendrin) transporter abundance, a pattern facilitating K+ and HCO3− secretion. After uninephrectomy, single-nephron GFR increased 50% and Li+ clearance doubled with both diets; in HK-alk versus HNa-LK, the increase in BP was less and ammoniagenesis was lower, abundance of proximal tubule transporters remained lower, ENaC-α fell, and NCCp increased, consistent with K+ conservation. After uninephrectomy, independent of diet, albuminuria increased eight-fold and abundance of endocytic receptors was reduced (megalin by 44%, disabled homolog 2 by 25%–35%) and kidney injury molecule-1 was increased.ConclusionsThe K-alkali–enriched diet blunted post-uninephrectomy hypertension and facilitated acid clearance by suppressing proximal Na+ transporters and increasing K+-alkali secretion. Furthermore, uninephrectomy-associated proteinuria could be attributed, at least in part, to elevated single-nephron GFR coupled with downregulation of megalin, which reduced fractional protein endocytosis and Vmax.PodcastThis article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2024_07_31_ASN0000000000000420.mp3

2024-09-01·Paediatric Respiratory Reviews

Pulmonary manifestations of Pseudohypoaldosteronism type 1b: A systematic review of the literature

Review

作者: Moudaki, Angeliki ; Chantzaras, Anastasios-Panagiotis ; Kaditis, Athanasios G. ; Koltsida, Georgia ; Kanaka-Gantenbein, Christina ; Panagiotou, Panagiota ; Kaditis, Athanasios G

INTRODUCTIONPseudohypoaldosteronism type 1b (PHA1B) is a rare autosomal recessive disease caused by dysfunction of amiloride-sensitive epithelial sodium channels (ENaC), that might present with a wide variety of pulmonary symptoms.METHODSWe provide a systematic review of published cases with PHA1B and respiratory symptoms, adding a relevant case from our clinic.RESULTSThirty-seven publications presenting 61 cases were identified apart from our case. Parental consanguinity was reported in 24/62 patients. In 39 patients the onset of pulmonary manifestations was early in infancy. Lower respiratory tract infections caused by Pseudomonas aeruginosa and Staphylococcus aureus were reported in 3 cases each, while 2 patients developed bronchiectasis. Pathological sweat test results were recorded in all 34 patients with available data. In 36/47 patients the underlying pathogenic variant was identified in SCNN1A gene.CONCLUSIONHigh clinical suspicion is required when treating patients with PHA1B for the potential need for early treatment of respiratory symptoms to avert any permanent pulmonary damage.

2024-08-27·Journal of Pediatric Endocrinology and Metabolism

Novel homozygous mutation in SCNN1A gene in an Iranian boy with PHA1B

Article

作者: Moghbelinejad, Sahar ; Saffari, Fatemeh ; Homaei, Ali ; Bahadoran, Ensiyeh

AbstractObjectivesPseudohypoaldosteronism type 1 (PHA1) has two genetically distinct variants, including renal and systemic forms. Systemic PHA type I (PHA1B) has varying degrees of clinical presentation and results from mutations in genes encoding subunits of the epithelial sodium channel (ENaC) including the alpha, beta, and gamma subunits. To date, about 45 variants of PHA1B have been identified.Case presentationWe report a boy with PHA1B, who presented with vomiting, lethargy, and poor feeding due to salt wasting six days after birth. The patient had electrolyte imbalances. A novel SCNN1A (sodium channel epithelial subunit alpha) gene mutation, NM_001038.6:c.1497G>C, with an autosomal recessive pattern, was identified by whole exosome sequencing. This variant was inherited as a homozygote from both heterozygous parents.ConclusionsPHA should be considered in neonates with hyponatremia and hyperkalemia. This case report presents a patient with a novel mutation in SCNN1A that has not been previously reported. Long-term follow-up of identified patients to understand the underlying phenotype-–genotype link is necessary.