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Intracellular platelet‐activating factor regulates eicosanoid generation in guinea‐pig resident peritoneal macrophages
Author(s) -
Stewart Alastair G.,
Phillips Wayne A.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb16874.x
Subject(s) - platelet activating factor , intracellular , extracellular , chemistry , guinea pig , prostacyclin , superoxide , arachidonic acid , endocrinology , biochemistry , medicine , pharmacology , biology , enzyme
1 The role of intracellular platelet‐activating factor (Paf) in arachidonic acid (AA) mobilization from guinea‐pig peritoneal macrophages has been investigated by use of the potent and selective Paf receptor antagonists, WEB 2086 and CV 6209. 2 Adherent macrophages contained cell‐associated Paf which was increased by exposure to formyl‐methionyl‐leucyl‐phenylalanine (fMLP), endotoxin and the ionophore, A23187. However, only endotoxin and A23187 caused release of detectable amounts of Paf into the extracellular medium. 3 Exogenous Paf and each of the above stimuli mobilized previously incorporated [ 14 C]‐AA and increased the generation of prostacyclin (PGI 2 ) in resident macrophages. 4 WEB 2086 (10–100 μ m ) and CV 6209 (0.1–10 μ m ) reduced both basal and stimulated PGI 2 generation and WEB 2086 inhibited the mobilization of [ 14 C]‐AA. In addition, WEB 2086 (10 μ m ) inhibited fMLP‐ and Paf‐induced superoxide anion generation. Responses to A23187 were not inhibited by either antagonist. 5 Activation of macrophages by fMLP caused a short burst of intracellular Paf generation but none was detected in the supernatants. The time‐course of PGI 2 synthesis followed closely that of Paf. 6 These data suggest that intracellular Paf generation is important for subsequent AA mobilization and may have a wider role in signal transduction processes.