Role of platelet-activating factor in phosphatidylcholine secretion in primary cultures of rat type II pneumocytes.
This study was designed to investigate the effect of platelet-activating factor (PAF) in the secretory response of type II pneumocytes, that are involved in the synthesis and secretion of the pulmonary surfactant. PAF increased phosphatidylcholine secretion in a concentration-dependent manner in the 10(-5) - 10(-10) M range, with a maximum phosphatidylcholine secretion of up to 3.3 fold the basal values (3.4 +/- 0.3% phosphatidylcholine secreted). This effect was prevented by the synthetic PAF-receptor antagonist WEB 2086. A study of the mechanism through which PAF exerts its stimulatory effect was carried out adding different agents that are well known stimulants of phosphatidylcholine secretion. Thus, PAF increased the TPA- and terbutaline-stimulated phosphatidylcholine secretion, that are PKC and PKA activators respectively, suggesting the involvement of both protein kinases in the process. This involvement was further supported by the use of inhibitors of protein kinases and by the stimulation of cAMP production in type II pneumocytes incubated with PAF.
Benito
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Department of Biochemistry and Molecular Biology, Faculty of Chemistry, Universidad Complutense, Madrid, Spain.
Bosch
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MA
D000818:Animals; D001381:Azepines / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010713:Phosphatidylcholines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D013997:Time Factors; D014230:Triazoles / Q000378:metabolism / Q000494:pharmacology
D001381:Azepines; D004791:Enzyme Inhibitors; D010713:Phosphatidylcholines; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C