PMID- 2553184 OWN - NLM STAT- MEDLINE DCOM- 19891219 LR - 20190510 IS - 0007-1188 (Print) IS - 0007-1188 (Linking) VI - 98 IP - 1 DP - 1989 Sep TI - Intracellular platelet-activating factor regulates eicosanoid generation in guinea-pig resident peritoneal macrophages. PG - 141-8 AB - 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 [14C]-AA and increased the generation of prostacyclin (PGI2) in resident macrophages. 4. WEB 2086 (10-100 microM) and CV 6209 (0.1-10 microM) reduced both basal and stimulated PGI2 generation and WEB 2086 inhibited the mobilization of [14C]-AA. In addition, WEB 2086 (10 microM) 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 PGI2 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. FAU - Stewart, A G AU - Stewart AG AD - Department of Physiology, University of Melbourne, Victoria, Australia. FAU - Phillips, W A AU - Phillips WA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Arachidonic Acids) RN - 0 (Azepines) RN - 0 (Culture Media) RN - 0 (Eicosanoids) RN - 0 (Platelet Activating Factor) RN - 0 (Triazines) RN - 0 (Triazoles) RN - 105219-56-5 (WEB 2086) RN - 11062-77-4 (Superoxides) RN - 27YG812J1I (Arachidonic Acid) RN - 37H9VM9WZL (Calcimycin) RN - 58962-34-8 (6-Ketoprostaglandin F1 alpha) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - 6-Ketoprostaglandin F1 alpha/biosynthesis MH - Animals MH - Arachidonic Acid MH - Arachidonic Acids/*metabolism MH - Azepines/pharmacology MH - Calcimycin/pharmacology MH - Chromatography, High Pressure Liquid MH - Culture Media MH - Dinoprostone/biosynthesis MH - Eicosanoids/*biosynthesis MH - Guinea Pigs MH - In Vitro Techniques MH - Macrophages/drug effects/*metabolism MH - Male MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - Peritoneal Cavity/cytology MH - Platelet Activating Factor/antagonists & inhibitors/biosynthesis/*physiology MH - Superoxides/metabolism MH - Triazines/pharmacology MH - *Triazoles PMC - PMC1854646 EDAT- 1989/09/01 00:00 MHDA- 1989/09/01 00:01 PMCR- 1990/09/01 CRDT- 1989/09/01 00:00 PHST- 1989/09/01 00:00 [pubmed] PHST- 1989/09/01 00:01 [medline] PHST- 1989/09/01 00:00 [entrez] PHST- 1990/09/01 00:00 [pmc-release] AID - 10.1111/j.1476-5381.1989.tb16874.x [doi] PST - ppublish SO - Br J Pharmacol. 1989 Sep;98(1):141-8. doi: 10.1111/j.1476-5381.1989.tb16874.x.