Adrenergic stimulation of Na+ transport across alveolar epithelial cells involves activation of apical Cl- channels.
Alveolar epithelial cells were isolated from adult Sprague-Dawley rats and grown to confluence on membrane filters. Most of the basal short-circuit current (Isc; 60%) was inhibited by amiloride (IC50 0. 96 microM) or benzamil (IC50 0.5 microM). Basolateral addition of terbutaline (2 microM) produced a rapid decrease in Isc, followed by a slow recovery back to its initial amplitude. When Cl- was replaced with methanesulfonic acid, the basal Isc was reduced and the response to terbutaline was inhibited. In permeabilized monolayer experiments, both terbutaline and amiloride produced sustained decreases in current. The current-voltage relationship of the terbutaline-sensitive current had a reversal potential of -28 mV. Increasing Cl- concentration in the basolateral solution shifted the reversal potential to more depolarized voltages. These results were consistent with the existence of a terbutaline-activated Cl- conductance in the apical membrane. Terbutaline did not increase the amiloride-sensitive Na+ conductance. We conclude that beta-adrenergic stimulation of adult alveolar epithelial cells results in an increase in apical Cl- permeability and that amiloride-sensitive Na+ channels are not directly affected by this stimulation.
Jiang
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Departments of Physiology and Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Ingbar
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O'Grady
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D004847:Epithelial Cells / Q000378:metabolism; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers; D013726:Terbutaline / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D018118:Chloride Channels; D011943:Receptors, Adrenergic, beta; D026941:Sodium Channel Blockers; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D012964:Sodium; D000242:Cyclic AMP; D013726:Terbutaline