Regulation of Cell Volume by β 2 -adrenergic Stimulation in Rat Fetal Distal Lung Epithelial Cells

Abstract

Cell-volume changes induced by terbutaline (a specific beta2-agonist) were studied morphometrically in rat fetal distal lung epithelium (FDLE) cells. Cell-volume changes qualitatively differed with the concentration of terbutaline. Terbutaline of 10(-10)-10(-8) M induced transient cell swelling. Terbutaline of 10(-7) M induced transient cell swelling followed by slow cell shrinkage. Terbutaline of 10(-6)-10(-5) M induced rapid cell shrinkage followed by slow cell shrinkage. Terbutaline of 10(-3) M induced transient cell shrinkage; then cell volume oscillated during stimulation. Benzamil of 10(-6) M suppressed the cell swelling induced by 10(-10)-10(-8) M terbutaline and quinine of 10(-3) M inhibited the cell shrinkage induced by 10(-6)-10(-5) M terbutaline. These results suggest that cell swelling would be induced by NaCl influx and the cell shrinkage is by KCl efflux. Dibutyryl cyclic AMP (DBcAMP) also induced similar cell-volume changes over a wide range of concentrations (10(-9)-10(-3) M): a low concentration induced transient cell swelling; a high concentration, rapid and slow cell shrinkage. Forskolin (10(-4) M), like terbutaline (10(-5) M), induced rapid cell shrinkage followed by slow cell shrinkage, and this decrease in the cell volume was enhanced by the presence of benzamil. On the other hand, cell shrinkage was induced by ionomycin (even low concentration; 3 x 10(-10) M ionomycin), and after that cell volume remained at a plateau level. Removal of extracellular Ca2+ abolished the cell swelling caused by terbutaline of 10(-10)-10(-8) M. With removal of extracellular Ca2+, the initial, rapid cell shrinkage induced by 10(-5) M terbutaline became transient, but we still detected slow cell shrinkage similar to that in the presence of extracellular Ca2+. Overall, at low concentrations (10(-10)-10(-8) M), terbutaline induced benzamil-sensitive cell swelling in FDLE cells, which was cAMP- and Ca2+-dependent; high concentrations (> or =10(-6)) induced quinine-sensitive rapid cell shrinkage, which was Ca2+-dependent; high concentrations (> or = 10(-7)) induced slow cell shrinkage, which was cAMP-dependent. These findings suggest that terbutaline regulates cell volume in FDLE cells by cytosolic cAMP and Ca2+ through activation of Na+ and K+ channels.