ATP-stimulated inositol phospholipid metabolism and surfactant secretion in rat type II pneumocytes.
Extracellular ATP (10(-3) M) stimulated [3H]phosphatidylcholine secretion approximately 3.4-fold in rat type II pneumocytes prelabeled overnight with [3H]choline. The same concentration of ATP caused a rapid increase in [3H]inositol trisphosphate (IP3) and a decrease in [3H]phosphatidylinositol bisphosphate (PIP2) in [3H]inositol-prelabeled cells. ATP also caused a biphasic increase in 1,2-[3H]diacylglycerol in cells prelabeled with [3H]arachidonic acid: a rapid increase that peaked at 10 s followed by a larger increase that peaked at 5-10 min. The first peak in diacylglycerol and the increase in IP3 are consistent with phospholipase C action on PIP2 and generation of second messengers that promote mobilization of intracellular Ca2+ and activation of protein kinase C. However, at the level of phosphatidylcholine secretion the stimulatory effects of ATP and of direct activators of protein kinase C, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1,2-dioctanoyl-sn-glycerol, were at least additive, suggesting that activation of protein kinase C may not be the major signal transduction mechanism in ATP action or alternatively that ATP activates a different isoform of protein kinase C. Pretreatment of type II cells with TPA for 30 min led to a subsequent 40% diminution in the stimulatory effects of ATP on both phosphatidylcholine secretion and IP3 generation.
Griese
M
M
Department of Pediatrics, Yale University, School of Medicine, New Haven, Connecticut 06510.
Gobran
L I
LI
Rooney
S A
SA
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010716:Phosphatidylinositols / Q000302:isolation & purification / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002712:Chlorides; D004075:Diglycerides; D007295:Inositol Phosphates; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D011663:Pulmonary Surfactants; D010566:Virulence Factors, Bordetella; D007294:Inositol; D000255:Adenosine Triphosphate; D008094:Lithium; D018021:Lithium Chloride; D002794:Choline; D013755:Tetradecanoylphorbol Acetate