ACTIVATION OF G-PROTEINS MAY INHIBIT OR STIMULATE SURFACTANT SECRETION IN RAT ALVEOLAR TYPE-II CELLS

To investigate how G proteins regulate surfactant secretion, we subjec ted rat alveolar type II cells to conditions known to activate or to i nactivate G proteins. AIF(4)(-), which activates G proteins, inhibited secretion in intact cells. Guanosine-5'-O-(3-thiotriphosphate), which activates G proteins in permeabilized cells, stimulated secretion at basal cytosolic [Ca2+], but inhibited secretion at higher [Ca2+]. In c ontrast, guanosine-5'-O-(2-thiodiphosphate) (GDP beta S), which inacti vates G proteins, stimulated secretion at each [Ca2+] tested. Because treatment with GDP beta S stimulated secretion at basal cytosolic [Ca2 +], surfactant secretion appears to be subject to G protein-regulated tonic inhibition. Pertussis toxin (PTX) inhibited terbutaline- and ion omycin-stimulated secretion in intact cells, but did not inhibit secre tion stimulated by either forskolin or 8-bromoadenosine 3',5'-cyclic m onophosphate. Inhibition by PTX of terbutaline-stimulated, but not 8-b romoadenosine 3',5'-cyclic monophosphate- or forskolin-stimulated secr etion, suggests that PTX-sensitive G proteins regulate beta-adrenergic -stimulated surfactant secretion proximal to second messenger generati on. Inhibition of ionomycin-stimulated secretion, however, suggests th at PTX-sensitive G proteins may also regulate non-receptor-mediated se cretory events.