Aldosterone Metabolism and Transepithelial Potential Difference in Normal and Cystic Fibrosis Subjects

Knowles, Michael R.; Gatzy, J. T.; Boucher, Richard C.

doi:10.1203/00006450-198507000-00008

Cited by 28 publications

(7 citation statements)

References 9 publications

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“…This is in agreement with a previous report demonstrating that aldosterone affects neither rabbit tracheal sodium transport (12) nor the nasal respiratory epithelial PD in normal subjects and patients with cystic fibrosis (28). These two reports and our data contrast with two other studies performed in the lung.…”

Section: Discussioncontrasting

confidence: 57%

Arginine Vasopressin and Atrial Natriuretic Peptide Do Not Alter Ion Transport by Cultured Fetal Distal Lung Epithelium

1992

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ABSTRAa. Previous studies have shown that i.v. arginine vasopressin (AVP) decreases but does not stop lung fluid secretion in term fetuses not in labor. Although it has been presumed that the response to AVP results from augmented sodium transport, there is controversy whether AVP actually does affect sodium transport in mammalian lung epithelium. To determine if AVP or aldosterone could alone or together augment sodium transport in the perinatal lung, we studied primary cultures of fetal rat distal lung epithelium in Ussing chambers. The short circuit current of these sodium-transporting cells was not affected by the application of either 30 or 300 mU/mL AVP whether or not they were previously exposed to aldosterone M). Aldosterone also did not affect the baseline bioelectric properties. Short circuit current increased in response to 8-bromo cAMP M) and 3-isobutyl-1-methylxanthine M) to levels 169 f 16 (SEM) and 172 f 7% of respective baseline values. AVP had no effect in cells pretreated with 3-isobutyl-1-methylxanthine. Monolayers also did not respond to atrial natriuretic peptide (lo-" to lo-' M). Monolayers of Na-absorbing A6 renal epithelium did increase short circuit current with either aldosterone or AVP. AVP increased endogenous cAMP levels in A6 but not fetal rat distal lung epithelium cells, suggesting that fetal rat distal lung epithelium lacks V2 receptors. These studies demonstrate that AVP does not increase ion ' transport in cultured fetal distal lung epithelium although these cells possess the necessary second messenger system. (Pediatr Res 31: 318-322,1992) Abbreviations AVP, arginine vasopressin FLE, fetal rat distal lung epithelium Isc, short circuit current IBMX, isobutyl-1-methylxanthine 8 Br, bromoadenosine HBSS, Hanks' balanced salt solution PD, potential difference R, resistance ANP, atrial natriuretic peptide MEM, minimum essential medium At birth, the newborn lung is filled with fluid, which must be cleared before efficient gas exchange can take place. Epithelial have demonstrated that the sodium transport blocker amiloride can block p-agonist-induced fluid absorption in the fetal lamb lung ( 1 ) and delay fluid clearance in newborn guinea piglets (2). Studies using amiloride analogs have also suggested that the ability of amiloride to delay postnatal lung water clearance results from its blockade of epithelial sodium channels (3). To investigate mechanisms that could increase this perinatal lung epithelial sodium transport, we chose to study AVP because it reduces fluid secretion in fetal goats ( 4 ) and lambs ( 5 ) and circulates in the fetus in increased concentrations during normal delivery (6).Numerous studies (e.g. Refs. 7-1 1 ) have demonstrated that AVP can increase sodium transport in some non-lung tissues by increasing the number of active membrane-associated sodium channels (10). It is unknown whether these observations can be extrapolated to different species or to different epithelial membranes. For example, it has been reported that the AVP increases sodium transport i...

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Section: Discussioncontrasting

confidence: 57%

Arginine Vasopressin and Atrial Natriuretic Peptide Do Not Alter Ion Transport by Cultured Fetal Distal Lung Epithelium

1992

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“…The implication that the activity of each ouabain bindinn site in CF is also increased merits further study. (30). Salt and water absorption by some epithelia and tissue oxidative metabolism are also stimulated by thyroid hormones (3 1).…”

Section: Discussionmentioning

confidence: 99%

Oxygen Consumption and Ouabain Binding Sites in Cystic Fibrosis Nasal Epithelium

et al. 1986

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ABSTRACT. Ion transport by the epithelium lining the airways of patients with cystic fibrosis (CF) is characterized by a raised transepithelial PD and an increased amiloride sensitivity (I). These properties could arise from normal sodium transport across an epithelium with decreased cell chloride permeability and limited chloride secretion. Alternatively, a higher than normal rate of sodium absorption could contribute to these abnormalities. We investigated the latter possibility by measuring oxygen consumption and specific ouabain binding of CF and atopic polyp epithelia and normal turbinate epithelium. Tissue from CF patients consumed oxygen at a rate that was two to three times that of non-CF tissues and had 60% more ouabain binding sites than non-CF epithelium. These results are not consistent with an isolated defect in chloride permeability but support recent findings that the sodium conductance of the apical cell membrane and net sodium absorption by CF nasal epithelium are greater than those of non-CF nasal epithelium. In CF, ion transport by airway epithelium is markedly abnormal (1, 2). The lumen negative PD generated in vivo by the nasal or tracheobronchial epithelium of CF patients is 2-to 3-fold greater than that of normal or disease control individuals (1) and hyperpolarizes less in response to superfusion with a chloridefree solution (3). Parallel findings in studies of sweat gland ductal epithelium have been interpreted as evidence for reduced membrane chloride permeability that traps salt in the duct lumen (4, 5). The more complete inhibition of airway PD by superfused amiloride, in vivo, is also consistent with the absence of a functioning chloride secretory path in CF airways (1, 2). Others have speculated, based on this reasoning, that the functional defect in CF airway epithelia is deficient chloride conductance (4). Alternatively, the greater amiloride eficacy and raised PD in CF airway epithelia could reflect both a decreased chloride permeability and an increased sodium absorptive rate.In epithelia that are dependent on operation of the Na+-K+-ATPase for ion transport, variations in transport rate can be paralleled by changes in indices of Na+-K+-ATPase activity. For example, increased ATP hydrolysis and numbers of sodium pumps have been found to accompany increases in sodium absorption by renal tubules (6) and chloride secretory capacity was paralleled by pump activity in shark rectal gland (7). In dog trachea, a predominantly chloride secreting airway epithelium, inhibition of chloride secretion caused a decrease in ouabainsensitive oxygen consumption (8). We reasoned that if the defect in cell chloride permeability in CF airways caused decreased chloride secretion, then hydrolysis of ATP by the Na+-K+-ATPase in CF cells would be normal or even reduced. On the other hand, if sodium absorption is increased in CF airway epithelium, then the synthesis and hydrolysis of ATP devoted to sodium pump activity should be greater than normal because of faster pump turnover and/or increased pump de...

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“…For example, dietary salt intake and circulating mineralocorticoid levels modulate ENaC activity in the kidney but do not affect ENaC function in airways (9). Similarly, while signals that raise intracellular cAMP in the kidney (e.g.…”

mentioning

confidence: 99%

Regulation of the Epithelial Sodium Channel by Serine Proteases in Human Airways

Donaldson¹,

Hirsh²,

Li³

et al. 2002

Journal of Biological Chemistry

229

223

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The epithelial sodium channel (ENaC) constitutes the rate-limiting step for sodium absorption across airway epithelia, which in turn regulates airway surface liquid (ASL) volume and the efficiency of mucociliary clearance. This role in ASL volume regulation suggests that ENaC activity is influenced by local factors rather than systemic signals indicative of total body volume homeostasis. Based on reports that ENaC may be regulated by extracellular serine protease activity in Xenopus and mouse renal epithelia, we sought to identify proteases that serve similar functions in human airway epithelia. Homology screening of a human airway epithelial cDNA library identified two trypsin-like serine proteases (prostasin and TMPRSS2) that, as revealed by in situ hybridization, are expressed in airway epithelia. Functional studies in the Xenopus oocyte expression system demonstrated that prostasin increased ENaC currents 60 -80%, whereas TMPRSS2 markedly decreased ENaC currents and protein levels. Studies of primary nasal epithelial cultures in Ussing chambers revealed that inhibition of endogenous serine protease activity with aprotinin markedly decreased ENaC-mediated currents and sensitized the epithelia to subsequent channel activation by exogenous trypsin. These data, therefore, suggest that protease-mediated regulation of sodium absorption is a function of human airway epithelia, and prostasin is a likely candidate for this activity.

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Aldosterone Metabolism and Transepithelial Potential Difference in Normal and Cystic Fibrosis Subjects

Cited by 28 publications

References 9 publications

Arginine Vasopressin and Atrial Natriuretic Peptide Do Not Alter Ion Transport by Cultured Fetal Distal Lung Epithelium

Arginine Vasopressin and Atrial Natriuretic Peptide Do Not Alter Ion Transport by Cultured Fetal Distal Lung Epithelium

Oxygen Consumption and Ouabain Binding Sites in Cystic Fibrosis Nasal Epithelium

Regulation of the Epithelial Sodium Channel by Serine Proteases in Human Airways

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