Interaction between sodium and chloride transport in bovine tracheal epithelium.

Langridge-Smith, Jane E.

doi:10.1113/jphysiol.1986.sp016155

Cited by 30 publications

(12 citation statements)

References 28 publications

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“…The similarities between amphibian epidermal, surface airway, and submucosal glandular epithelia with respect to highly regulated CFTR expression is intriguing and suggests that similar mechanisms of regulating ion conductances may exist between these model systems. Such a hypothesis for cell-type specific regulation of Na + and Cl -conductance in bovine tracheal epithelium has been previously suggested 97,98 and is highlighted in Figure 2c. If this hypothesis is true, gene targeting to correct Gene therapy of CF lung disease Q Jiang and JF Engelhardtchloride secretory defects may encompass different cell types than those necessary to achieve correction of Na + absorption defects.…”

Section: Transport In Electrically-tight Epitheliamentioning

confidence: 89%

Cellular heterogeneity of CFTR expression and function in the lung: implications for gene therapy of cystic fibrosis

Jiang

Engelhardt

1998

Eur J Hum Genet

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Cystic fibrosis (CF) has become a paradigm disorder for the clinical testing of gene therapies in the treatment of inherited disease. In recent years, efforts directed at gene therapy of CF have concentrated on improving gene delivery systems to the airway. Surrogate endpoints for complementation of CFTR dysfunction in the lung have been primarily dependent on correction of chloride transport abnormalities. However, it is now clear that the pathophysiology of CF airways disease is far more complex than can be solely attributed to altered chloride permeability. For example, in addition to functioning as a chloride channel, CFTR also has been implicated in the regulation of other apical membrane conductance pathways through interactions with the amiloride sensitive epithelial sodium channel (ENaC) and the outwardly rectifying chloride channel (ORCC). Superimposed on this functional diversity of CFTR is a highly regulated pattern of CFTR expression in the lung. This heterogeneity occurs at both the level of CFTR protein expression within different cell types in the airway and the anatomical location of these cells in the lung. Potential targets for gene therapy of CF include ciliated, non-ciliated, and goblet cells in the surface airway epithelium as well as submucosal glands within the interstitium of the airways. Each of these distinct cellular compartments may have functionally distinct roles in processes which affect the pathogenesis of CF airways disease, such as fluid and electrolyte balance. However, it is presently unclear which of these cellular targets are most pathophysiologic relevant with regard to gene therapy. Elucidation of the underlying mechanisms of CFTR function in the airway will allow for the rational design of gene therapy approaches for CF lung diseases. This review will provide a summary of the field's current knowledge regarding CFTR functional diversity in the airway and the implications of such diversity for gene therapies of CF lung disease.

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Section: Transport In Electrically-tight Epitheliamentioning

confidence: 89%

Cellular heterogeneity of CFTR expression and function in the lung: implications for gene therapy of cystic fibrosis

Jiang

Engelhardt

1998

Eur J Hum Genet

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“…5). It is possible that, (4,30). These observations may be important in understanding abnormalities of airway epithelial ion transport in cystic fibrosis (CF).…”

Section: Resultsmentioning

confidence: 99%

Regulation of sodium absorption by canine tracheal epithelium.

Cullen¹,

Welsh²

1987

J. Clin. Invest.

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To regulate the quantity of respiratory tract fluid, the airway epithelium either secretes chloride, Cl-, or reabsorbs sodium, Na'. Many secretagogues inhibit Na' absorption, but the decrease may result from a fall in the electrochemical gradient for Na' absorption. We examined regulation of Na' absorption independent of CL-secretion, by bathing canine tracheal epithelium in Cl--free, gluconate Ringers solution. Prostaglandin E2, 2-chloroadenosine, and isoproterenol increased short-circuit current (Isc) and the rate of Na' absorption. In contrast, indomethacin, which inhibits endogenous prostaglandin production, decreased Isc. These agents regulate cellular levels ofcAMPY, direct addition of 8-Br-cAMP also acutely increased Isc. We examined chronic regulation of Na' absorption in cell monolayers grown on permeable supports in serum-free media. Exposure to aldosterone for two days increased baseline Isc by 50% and the amilorideinhibitable current by 55%. These data indicate that Na' absorption is both acutely and chronically regulated in the airway epithelium.

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“…Secondly we aimed at investigating the dietary and hormonal influences on the regulation of coprodeal CI transport. Thirdly, after having found profound alterations in C1 secretion, we aimed at tracing the epithelial and cellular site of C1 secretion, e.g., to tackle the question if distinct cells are involved in either Na-or Cl-transport (Langridge- Smith, 1985Smith, , 1986.…”

Section: Introductionmentioning

confidence: 99%

A low-salt diet facilitates Cl secretion in hen lower intestine

Clauss

Dantzer²,

Skadhauge³

1988

J. Membrain Biol.

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The regulation of sodium and chloride transport in hen coprodeum by mineralocorticoids was investigated with isolated epithelia under short-circuit conditions. Unidirectional fluxes of Na and Cl were measured by isotopes and modulated by amiloride, theophylline and bumetanide. Hens were maintained either on low-NaCl diet (LS) or on high-NaCl diet (HS). Plasma aldosterone (PA) levels of these groups were measured with radioimmunoassay. A group of HS hens received injections of aldosterone on a 6-hr schedule before experiments. Another group of LS hens was resalinated, and experiments carried out on a 24-hr interval. Salt deprivation stimulated PA levels ninefold, compared to HS hens. Na absorption was stimulated according to previous reports. Electrogenic Cl secretion was elicited by theophylline and partially inhibited by bumetanide. Modulation of PA levels by diet, resalination or aldosterone injection changed the magnitude of electrogenic Cl secretion in parallel between 0.5 mueq/cm2.hr (HS) and 4 mueq/cm2.hr (LS), with pronounced alteration in tissue resistance. The results demonstrate a new action of aldosterone which besides stimulating Na absorption also directly or indirectly elicits Cl secretion. Evidence is presented for a hormonal adaptation of chloride transport in this epithelium. There was a morphological change of the apical plasma membrane and further experiments will have to clarify the exact cellular nature of this process.

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Interaction between sodium and chloride transport in bovine tracheal epithelium.

Cited by 30 publications

References 28 publications

Cellular heterogeneity of CFTR expression and function in the lung: implications for gene therapy of cystic fibrosis

Cellular heterogeneity of CFTR expression and function in the lung: implications for gene therapy of cystic fibrosis

Regulation of sodium absorption by canine tracheal epithelium.

A low-salt diet facilitates Cl secretion in hen lower intestine

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