STIMULATION OF PHOSPHATIDYLCHOLINE HYDROLYSIS IN TYPE-II ALVEOLAR EPITHELIAL-CELLS

The effects of phorbol 12-myristate 13-acetate (TPA) or ATP on phosphatidylcholine (PC) hydrolysis were investigated in cultured type II pneumocytes prelabeled with [H-3]choline or 1-O-[H-3]octadecyl-sn-glycero-3-phosphocholine ([H-3]lyso-PAF). In cells prelabeled with [H-3]choline, TPA or ATP stimulated an increase in [H-3]choline, [H-3]phosphocholine, and [H-3]glycerophosphocholine. The formation of these choline metabolites was associated with a concomitant loss of [H-3]PC but not from disaturated PC or phosphatidylinositol. In cells prelabeled with [H-3]lyso-PAF, the formation of [H-3]phosphatidic acid (PA) and then [H-3]1,2-DG was stimulated by TPA or ATP and was associated with a loss of H-3 from PC but not from disaturated PC or phosphatidylinositol. There was a concentration-dependent formation of [H-3]1,2-DG and [H-3]PA in response to ATP. Downregulation of protein kinase C with TPA abolished the stimulation of PC hydrolysis. In addition to the generation of metabolites indicative of phospholipase C and/or D activity, [H-3]lyso-PC, a product of phospholipase A2, was also generated in response to TPA. These findings suggest an important role for PC breakdown in signal transduction in type II pneumocytes.