Effects of Ca(2+) channel blockers on amiloride-sensitive Na(+) permeable channels and Na(+) transport in fetal rat alveolar type II epithelium.
A beta-adrenergic agonist (beta-agonist), terbutaline, stimulated amiloride-sensitive Na(+) absorption in fetal rat alveolar type II epithelium, contributing to the clearance of lung fluid. Cytosolic Ca(2+) plays an important role in terbutaline-stimulated Na(+) absorption, since Ca(2+)-activated, amiloride-sensitive Na(+)-permeable channels are involved in transcellular Na(+) absorption and terbutaline stably elevates the cytosolic Ca(2+) concentration by stimulating Ca(2+) influx. Therefore, we studied whether Ca(2+) channel blockers (Ni(2+), verapamil, and nifedipine) affect terbutaline-stimulated transcellular Na(+) absorption. Ni(2+) partially blocked the channel responsible for the terbutaline-stimulated Na(+) absorption at the Na(+) entry pathway across the apical membrane of the epithelium, but did not diminish the terbutaline-stimulated transcellular Na(+) absorption. By measuring the capacity of the Na(+),K(+)-pump activity, we determined that the rate-limiting step of the terbutaline-stimulated transcellular Na(+) absorption was the extrusion step across the basolateral membrane by the Na(+),K(+)-pump. The other Ca(2+) channel blockers, verapamil and nifedipine, had effects identical to those of Ni(2+). Based upon these observations, we conclude that, in the beta-agonist-stimulated fetal rat alveolar type II epithelium, Ca(2+) channel blockers diminish amiloride-sensitive channels, but do not affect transcellular Na(+) absorption, since under the beta-agonist-stimulated condition the Na(+),K(+)-pump is the rate-limiting step in Na(+) transport.
Marunaka
Yoshinori
Y
Department of Cellular and Molecular Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan. marunaka@basic.kpu-m.ac.jp
Niisato
Naomi
N
D000584:Amiloride / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001692:Biological Transport; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology; D004347:Drug Interactions; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004232:Diuretics; D011943:Receptors, Adrenergic, beta; D015222:Sodium Channels; D000584:Amiloride; D012964:Sodium; D014700:Verapamil; D009543:Nifedipine