The effect of brefeldin A on terbutaline-induced sodium absorption in fetal rat distal lung epithelium.
We studied the effect of brefeldin A, which inhibits the intracellular trafficking of membrane proteins from the cytosolic pool to the cell surface, on terbutaline (a beta2-specific adrenergic agonist)-induced alterations in ion transport by primary monolayer cultures of fetal rat distal lung epithelium. The amiloride-sensitive short circuit current (Isc) increased 2.5-fold 50 min after application of terbutaline (10 microM) from basolateral side; this response was abolished by pretreatment with brefeldin A (1 microg/ml). Brefeldin A did not suppress the Na+/K+ pump capacity. Single channel patch clamp experiments demonstrated that terbutaline increased the density of amiloride-sensitive Na+-permeable nonselective cation channels on the apical cell membrane and this action was blocked by brefeldin A. These observations suggest that beta2-specific adrenergic agonists promote the trafficking of amiloride sensitive Na+-permeable nonselective cation channels to the apical cell surface.
Ito
Y
Y
MRC Group in Lung Development and Division of Respiratory Research Hospital for Sick Children research Institute University of Toronto Faculty of Medicine Toronto, Ontario M5G 1X8, Canada.
Niisato
N
N
O'Brodovich
H
H
Marunaka
Y
Y
D000042:Absorption / Q000187:drug effects; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D020126:Brefeldin A; D002412:Cations / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology*; D004848:Epithelium / Q000196:embryology; D005333:Fetus / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008168:Lung / Q000196:embryology*; D018408:Patch-Clamp Techniques; D051381:Rats / Q000196:embryology; D017208:Rats, Wistar; D012964:Sodium / Q000493:pharmacokinetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013726:Terbutaline / Q000494:pharmacology*
D002412:Cations; D003517:Cyclopentanes; D007473:Ion Channels; D020126:Brefeldin A; D000584:Amiloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D013726:Terbutaline