Adrenergic regulation of ion transport across adult alveolar epithelial cells: effects on Cl- channel activation and transport function in cultures with an apical air interface.
The effect of beta-adrenergic receptor stimulation on Cl- channel activation was investigated in alveolar epithelial cells grown in monolayer culture and in freshly isolated cells. Monolayers cultured under apical air interface conditions exhibited enhanced amiloride-sensitive Na+ transport compared to apical liquid interface monolayers. Amiloride or benzamil inhibited most (66%) of the basal short circuit current (Isc) with half-maximal inhibitory concentration (IC50) values of 0.62 microm and 0.09 microm respectively. Basolateral addition of terbutaline (2 microm) produced a rapid decrease in Isc followed by a slow recovery that exceeded the basal Isc. When Cl- was replaced with methanesulfonate in either intact monolayers or basolateral membrane permeabilized monolayers, the response to terbutaline (2 microm) was completely inhibited. No effect of terbutaline on amiloride-sensitive Na+ current was detected. beta-Adrenergic agonists and 8-chlorothiophenyl cyclic adenosine monophosphate (8-ctp cAMP) directly stimulated a Cl- channel in freshly isolated alveolar epithelial cells. The current was blocked by glibenclamide (100 microm) and had a reversal potential of -22 mV. No increase in amiloride-sensitve current was detected in response to terbutaline or 8-cpt cAMP stimulation. These data support the conclusion that beta-adrenergic agonists produce acute activation of apical Cl- channels and that monolayers maintained under apical air interface conditions exhibit increased Na+ absorption.
Jiang
X
X
Department of Physiology, University of Minnesota, St. Paul, MN 55108, USA.
Ingbar
D H
DH
O'Grady
S M
SM
D018663:Adrenergic Agents / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000388:Air; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D016764:Cell Polarity; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D015640:Ion Channel Gating / Q000187:drug effects*; D017136:Ion Transport / Q000187:drug effects*; D008297:Male; D009579:Nitrobenzoates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D013726:Terbutaline / Q000494:pharmacology
D018663:Adrenergic Agents; D000318:Adrenergic beta-Agonists; D018118:Chloride Channels; D002712:Chlorides; D009579:Nitrobenzoates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C085057:4-nitro-2-(3-phenylpropylamino)benzoate; D000584:Amiloride; D012964:Sodium; D013726:Terbutaline; D005905:Glyburide