REGULATION OF CELL-VOLUME BY BETA(2)-ADRENERGIC STIMULATION IN RAT FETAL DISTAL LUNG EPITHELIAL-CELLS

Cell-volume changes induced by terbutaline (a specific beta(2)-agonist ) were studied morphometrically in rat fetal distal lung epithelium (F DLE) cells. Cell-volume changes qualitatively differed with the concen tration of terbutaline. Terbutaline of 10(-10)-10(-8) M induced transi ent cell swelling. Terbutaline of 10(-7) M induced transient cell swel ling followed by slow cell shrinkage. Terbutaline of 10(-6)-10(-5) M i nduced rapid cell shrinkage followed by slow cell shrinkage. Terbutali ne of 10(-3) M induced transient cell shrinkage; then cell volume osci llated during stimulation. Benzamil of 10(-6) M suppressed the cell sw elling 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 infl ux and the cell shrinkage is by KCl efflux. Dibutyryl cyclic AMP (DBcA MP) also induced similar cell-volume changes over a wide range of conc entrations (10(-9)-10(-3) M): a low concentration induced transient ce ll swelling; a high concentration, rapid and slow cell shrinkage. Fors kolin (10(-4) M), like terbutaline (10(-5) M), induced rapid cell shri nkage followed by slow cell shrinkage, and this decrease in the cell v olume was enhanced by the presence of benzamil. On the other hand, cel l shrinkage was induced by ionomycin (even low concentration; 3 x 10(- 10) M ionomycin), and after that cell volume remained at a plateau lev el. Removal of extracellular Ca2+ abolished the cell swelling caused b y terbutaline of 10(-10)-10(-8) M. With removal of extracellular Ca2+, the initial, rapid cell shrinkage induced by 10(-5) M terbutaline bec ame transient, but we still detected slow cell shrinkage similar to th at in the presence of extracellular Ca2+. Overall, at low concentratio ns (10(-10)-10(-8) M), ter-butaline induced benzamil-sensitive cell sw elling in FDLE cells, which was cAMP- and Ca2+-dependent; high concent rations (greater than or equal to 10(-6)) induced quinine-sensitive ra pid cell shrinkage, which was Ca2+-dependent; high concentrations (gre ater than or equal to 10(-7)) induced slow cell shrinkage, which was c AMP-dependent. These findings suggest that terbutaline regulates cell volume in FDLE cells by cytosolic cAMP and Ca2+ through activation of Na+ and K+ channels.