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 mu M) 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).