Alveolar epithelial CNGA1 channels mediate cGMP-stimulated, amiloride-insensitive, lung liquid absorption

2011 ◽  
Vol 462 (2) ◽  
pp. 267-279 ◽  
Author(s):  
William J. Wilkinson ◽  
Audra R. Benjamin ◽  
Ian De Proost ◽  
Maria C. Orogo-Wenn ◽  
Yasuo Yamazaki ◽  
...  
Keyword(s):  
Alveolar Epithelial ◽  
Liquid Absorption ◽  
Lung Liquid ◽  
Cnga1 Channels

Dibutyryl cAMP induces a gestation-dependent absorption of fetal lung liquid

1990 ◽  
Vol 68 (5) ◽  
pp. 2054-2059 ◽  
Author(s):  
D. V. Walters ◽  
C. A. Ramsden ◽  
R. E. Olver
Keyword(s):  
Fetal Lung ◽  
Liquid Volume ◽  
Intracellular Camp ◽  
Maximal Effect ◽  
Dibutyryl Camp ◽  
Rate Limiting Step ◽  
Liquid Absorption ◽  
Dependent Absorption ◽  
Lung Liquid ◽  
Rate Limiting

The maturation of the adenosine 3′,5′-cyclic monophosphate-(cAMP) dependent pathway controlling fetal lung liquid secretion was examined in experiments in which the lungs of chronically catheterized fetal lambs (123-141 days gestational age) were exposed to dibutyryl cAMP (DBcAMP, 10(-4) M). The effect of DBcAMP was markedly gestation dependent, with the greatest effect observed in the most mature fetuses. In immature fetuses (less than 130 days, mean age 125 days) DBcAMP caused slowing of secretion, with maximal effect at 5 h. With increasing maturity the effect of DBcAMP was more pronounced and occurred earlier so that in mature fetuses (mean age 140 days) lung liquid absorption took place, with maximal effect at 2 h. Changes in lung liquid volume flow induced by DBcAMP could be blocked by addition of 10(-4) M amiloride to lung liquid. It is concluded that 1) DBcAMP induces a change in lung liquid secretion that, like epinephrine, is mediated via an increase in Na+ permeability of the apical membrane of the lung epithelium and 2) the rate-limiting step in the maturation of this process must lie beyond the generation of intracellular cAMP.

Halothane and Isoflurane Decrease Alveolar Epithelial Fluid Clearance in Rats 

1998 ◽  
Vol 88 (3) ◽  
pp. 751-760 ◽  
Author(s):  
Saida Rezaiguia-Delclaux ◽  
Christian Jayr ◽  
Deng Feng Luo ◽  
Nor-Eddine Saidi ◽  
Michel Meignan ◽  
...  
Keyword(s):  
Protein Concentration ◽  
Intratracheal Instillation ◽  
Alveolar Fluid Clearance ◽  
Albumin Solution ◽  
Alveolar Epithelial ◽  
Control Value ◽  
Primary Mechanism ◽  
Lung Liquid ◽  
Alveolar Liquid Clearance ◽  
Alveolar Liquid

Background Active sodium transport is the primary mechanism that drives alveolar fluid clearance. In the current study, the effects of exposure to halothane and isoflurane on alveolar fluid clearance in rats were evaluated. Methods Rats were exposed to either halothane (0.4% for 6 h or 2% for 2 h) or isoflurane (0.6% for 6 h or 2.8% for 2 h). Reversibility of halothane effects was assessed after 2 h of exposure to 2% halothane. Alveolar and lung liquid clearance were measured by intratracheal instillation of a 5% albumin solution with 1.5 microCi of 125I-albumin, during mechanical ventilation with 100% FiO2 and the halogenated agent. The effect of terbutaline (10(-4) M) added to the albumin solution was tested after 2 h of exposure to 2% halothane. The increase in protein concentration in the airspaces over 1 h was used to evaluate alveolar liquid clearance. Lung liquid clearance was calculated gravimetrically. Results Alveolar liquid clearance rates were decreased by 24%, 30% and 40% compared with controls (P < 0.05) after 2 h of exposure to halothane, 6 h of exposure to halothane, and 6 h of exposure to isoflurane, respectively. After 2 h of exposure to isoflurane, alveolar liquid clearance did not change. In the 2-h halothane exposure group, alveolar liquid clearance returned to the control value 2 h after withdrawal of halothane. Terbutaline increased alveolar liquid clearance by 50% and 89% in the control and 2-h halothane exposure groups, respectively. In all experiments, the same results were obtained for alveolar and lung liquid clearance. Conclusions Halothane and isoflurane caused a reversible decrease in alveolar epithelial fluid clearance. Two hours of exposure to halothane did not alter the stimulatory effect of terbutaline on alveolar liquid clearance.

Invited Review: Clearance of lung liquid during the perinatal period

2002 ◽  
Vol 93 (4) ◽  
pp. 1542-1548 ◽  
Author(s):  
Pierre M. Barker ◽  
Richard E. Olver
Keyword(s):  
Developmental Regulation ◽  
Perinatal Period ◽  
Lung Epithelium ◽  
Physiological Mechanisms ◽  
Transgenic Cell ◽  
Membrane Transport Proteins ◽  
Liquid Absorption ◽  
Clinical Consequences ◽  
Distal Lung ◽  
Lung Liquid

At birth, the distal lung epithelium undergoes a profound phenotypic switch from secretion to absorption in the course of adaptation to air breathing. In this review, we describe the developmental regulation of key membrane transport proteins and the way in which epinephrine, oxygen, glucocorticoids, and thyroid hormones interact to bring about this crucial change in function. Evidence from molecular, transgenic, cell culture, and whole lung studies is presented, and the clinical consequences of the failure of the physiological mechanisms that underlie perinatal lung liquid absorption are discussed.

Active sodium transport and alveolar epithelial Na-K-ATPase increase during subacute hyperoxia in rats

1994 ◽  
Vol 266 (5) ◽  
pp. L577-L584 ◽  
Author(s):  
W. Olivera ◽  
K. Ridge ◽  
L. D. Wood ◽  
J. I. Sznajder
Keyword(s):  
Lung Injury ◽  
Lung Edema ◽  
Type Ii ◽  
Active Sodium ◽  
Na Transport ◽  
Alveolar Epithelial ◽  
Oxygen Exposure ◽  
Isolated Lung ◽  
Injured Lung ◽  
Lung Liquid

Active Na+ transport and lung edema clearance were studied in a model of lung injury caused by sublethal oxygen exposure. Rats exposed to 85% O2 for 7 days were studied at 0, 7, 14, and 30 days after removal from the hyperoxic chamber and compared with room air controls. In the isolated-perfused, fluid-filled rat lung, albumin flux from the perfusate into the air spaces increased after oxygen exposure and returned to control values after 7 days of recovery. However, permeability to small solutes (Na+ and mannitol) normalized only after 30 days of recovery from hyperoxia. Active Na+ transport increased immediately after oxygen exposure and returned to control values 7 days after removal from hyperoxic chamber. Na-K-adenosinetriphosphatase (ATPase) activity, and protein expression in alveolar epithelial type II cells obtained at the end of the isolated lung experiments increased significantly after the oxygen exposure compared with controls in association with the increased active Na+ transport. We conclude that active Na+ transport and lung liquid clearance are increased in the subacute hyperoxic phase of lung injury in rats, due in part to the upregulation of alveolar epithelial Na-K-ATPases. Conceivably, this behavior protects against the effects of lung injury by allowing the injured lung to clear edema more effectively. Accordingly, this upregulation may be targeted as a strategy to diminish edema in patients with lung injury.

scholarly journals Lack of a role for cyclic nucleotide gated cation channels in lung liquid absorption in fetal sheep

2000 ◽  
Vol 523 (2) ◽  
pp. 493-502 ◽  
Author(s):  
R. W. J. Junor ◽  
A. R. Benjamin ◽  
D. Alexandrou ◽  
S. E. Guggino ◽  
D. V. Walters
Keyword(s):  
Cyclic Nucleotide ◽  
Cation Channels ◽  
Fetal Sheep ◽  
Liquid Absorption ◽  
Lung Liquid

Downregulation of ENaC activity and expression by TNF-α in alveolar epithelial cells

2004 ◽  
Vol 286 (2) ◽  
pp. L301-L311 ◽  
Author(s):  
André Dagenais ◽  
Rosalie Fréchette ◽  
Yuko Yamagata ◽  
Toshiyuki Yamagata ◽  
Jean-François Carmel ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mrna Expression ◽  
Proinflammatory Cytokine ◽  
Alveolar Epithelial Cells ◽  
Sodium Absorption ◽  
Lung Edema ◽  
Alveolar Epithelial ◽  
Tnf Α ◽  
Lung Liquid ◽  
Factor Α

Sodium absorption by an amiloride-sensitive channel is the main driving force of lung liquid clearance at birth and lung edema clearance in adulthood. In this study, we tested whether tumor necrosis factor-α (TNF-α), a proinflammatory cytokine involved in several lung pathologies, could modulate sodium absorption in cultured alveolar epithelial cells. We found that TNF-α decreased the expression of the α-, β-, and γ-subunits of epithelial sodium channel (ENaC) mRNA to 36, 43, and 16% of the controls after 24-h treatment and reduced to 50% the amount of α-ENaC protein in these cells. There was no impact, however, on α1and β1Na+-K+-ATPase mRNA expression. Amiloride-sensitive current and ouabain-sensitive Rb+uptake were reduced, respectively, to 28 and 39% of the controls. A strong correlation was found at different TNF-α concentrations between the decrease of amiloride-sensitive current and α-ENaC mRNA expression. All these data show that TNF-α, a proinflammatory cytokine present during lung infection, has a profound influence on the capacity of alveolar epithelial cells to transport sodium.

scholarly journals The Independence of Lung Liquid Absorption in Postnatal Sheep on Pulmonary Blood Flow, Blood Gases or Perfusion Pressure

2001 ◽  
Vol 86 (3) ◽  
pp. 391-398 ◽  
Author(s):  
R. W. J. Junor ◽  
A. R. Benjamin ◽  
D. Alexandrou ◽  
D. V. Walters
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Perfusion Pressure ◽  
Blood Gases ◽  
Liquid Absorption ◽  
Lung Liquid
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