Abstract
Tumor promoter 12–0–tetradecanoylphorbol 13-acetate (TPA) is a potent secretagogue for surfactant release from lung: its mechanism of action remains unknown. Since TPA activates a Ca2+, phospholipid (PL) C-kinase in other cells we tested whether TPA alters surfactant release from isolated Type II cells in a Ca2+ dependent fashion and whether polymixin B, a known inhibitor of C-kinase, blocks effects of TPA. TPA caused a dose dependent release of 3H-choline labelled phosphatidylcholine (3H-PC) from purified rat Type II cells in primary culture:
TPA was not toxic as monitored by lactate dehydrogenase release. Since C-kinase is a Ca2+ PL dependent enzyme, effects of calcium ionophore A23187 and TPA together on surfactant release were studied. TPA-induced (100nM) 3H-PC release was significantly potentiated by A23187 (10nM): Control 1.40±0.23%; A23187 1.61±.24%; TPA 3.30±0.40%; A23187+TPA 5.63±0.39% (p<0.001 for A23187+TPA vs. controU p<0.05 for TPA vs. control). Polymixin B, a known inhibitor of Ca2+ -PL kinase, partially blocked TPA-induced 3H-PC release: Control 1.17±0.17%; polymixin B 0.40±0.08%; TPA 4.07±0.34%; TPA+polymixin B 2.43±0.29% (p<0.05 for TPA vs. control and TPA+polymixin B vs. polymixin B alone). These data provide support for C-kinase involvement in regulation of TPA-induced surfactant secretion. Supported by the American Lung Association, NIH-HL-28623 and HD-11725.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rice, W., Singleton, F., Lorow, D. et al. 305 REGULATION OF SURFACTANT SECRETION FROM TYPE II CELLS MECHANISM OF TUMOR PROMOTER ACTION. Pediatr Res 19, 161 (1985). https://doi.org/10.1203/00006450-198504000-00335
Issue Date:
DOI: https://doi.org/10.1203/00006450-198504000-00335