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 [3H]choline or 1-O-[3H]octadecyl-sn-glycero-3-phosphocholine ([3H]lyso-PAF). In cells prelabeled with [3H]choline, TPA or ATP stimulated an increase in [3H]choline, [3H]phosphocholine, and [3H]glycerophosphocholine. The formation of these choline metabolites was associated with a concomitant loss of [3H]PC but not from disaturated PC or phosphatidylinositol. In cells prelabeled with [3H]lyso-PAF, the formation of [3H]phosphatidic acid (PA) and then [3H]1,2-DG was stimulated by TPA or ATP and was associated with a loss of 3H from PC but not from disaturated PC or phosphatidylinositol. There was a concentration-dependent formation of [3H]1,2-DG and [3H]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, [3H]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.
Dubrovin
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LC
Department of Pediatrics, Emory University, Atlanta, Georgia 30322.
Brown
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LA
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006868:Hydrolysis / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D010713:Phosphatidylcholines; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D002794:Choline; D013755:Tetradecanoylphorbol Acetate