Beta 2-agonist regulation of cell volume in fetal distal lung epithelium by cAMP-independent Ca2+ release from intracellular stores.
The effects of beta 2-adrenoceptor agonist (beta 2 agonist) and cAMP on cytosolic Ca2+ concentration ([Ca2+]c) and cell volume were studied in fetal distal lung epithelial cells. Both terbutaline (a specific beta 2 agonist, 10 microM) and dibutyryl cAMP (DBcAMP, 1 mM) increased [Ca2+]c in the presence of extracellular Ca2+. Even in the absence of extracellular Ca2+, the terbutaline-induced increase in [Ca2+]c was still observed, although the increase was transient. However, DBcAMP caused no significant change in [Ca2+]c. In the presence of 1 mM extracellular Ca2+, terbutaline and DBcAMP induced quinine (a blocker of K+ channel) sensitive cell shrinkage. However, in a Ca2(+)-free solution, terbutaline induced rapid cell shrinkage, followed by benzamil (a specific blocker of Na+ channel, an analogue of amiloride) sensitive transient cell swelling. In a Ca2(+)-free solution, DBcAMP induced benzamil-sensitive transient cell swelling without cell shrinkage. Taken together, our observations indicate that the beta 2 agonist induced an elevation of [Ca2+]c by increasing both a Ca2+ influx from the extracellular space and a Ca2+ release from intracellular Ca2+ stores, whereas DBcAMP only stimulated Ca2+ influx from the extracellular space. Furthermore, it is suggested that terbutaline and DBcAMP activated benzamil-sensitive channels independently of an increase in [Ca2+]c.
Niisato
N
N
Division of Respiratory Research, Hospital for Sick Children, University of Toronto, Faculty of Medicine, ON, Canada.
Nakahari
T
T
Tanswell
A K
AK
Marunaka
Y
Y
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size; D000242:Cyclic AMP / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005333:Fetus; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013726:Terbutaline / Q000494:pharmacology*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000242:Cyclic AMP; D013726:Terbutaline; D002118:Calcium