Mechanisms of mastoparan-stimulated surfactant secretion from isolated pulmonary alveolar type 2 cells.

摘要: Mastoparan, a tetradecapeptide component of wasp venom, is potent activator secretion in variety cell types, and has been shown to activate purified G-proteins reconstituted into phospholipid vesicles with preferential activation Gi over Gs (Higashijima, T., Uzu, S., Nakajima, Ross, E. R. (1988) J. Biol. Chem. 263, 6491-6494). To identify the biochemical activities mastoparan cellular system, we characterized effects on signal transduction pathways rat pulmonary alveolar type 2 epithelial cells, which synthesize secrete surfactant. Mastoparan inhibited adenylylcyclase activity manner that was dose-dependent (IC50 = 30 microM), but sensitive neither guanine nucleotide nor pertussis toxin (PT). induced PT-sensitive increase inositol trisphosphate rapid rise cytosolic calcium released from intracellular stores; time onset rise, rate amplitude were PT-sensitive. also caused dose- (EC50 16 microM) time-dependent arachidonic acid release completely insensitive pretreatment PT. Secretion surfactant increased by approximately 8-fold constitutive levels at 1 h an EC50 20 microM, mastoparan-stimulated partially PT late points inhibitors metabolism, not protein kinase C inhibitor H7. These findings are consistent proteins cells mastoparan, although lack predicted triphosphoguanine sensitivity for some indicates does act strictly analogous liganded receptors or mediated Gi. While secretagogue several its secretory appears have only limited dependence cells.