Involvement of eicosanoids in platelet-activating factor-induced modulation of adenylyl cyclase activity in alveolar macrophages.
Platelet-activating factor (PAF) induces a dose-dependent biphasic response in adenylyl cyclase activity in antigen-challenged alveolar macrophages (AM), but not in naive AM. Intracellular cyclic AMP levels are enhanced by very low concentrations of PAF (10(-13)-10(-10) M) and decreased by higher PAF concentrations (10(-8)-10(-5) M). The PAF response of adenylyl cyclase could be completely blocked by pretreatment with the PAF receptor antagonist BN 52021. The adenylyl cyclase stimulatory and inhibitory phases are reversed by indometacin (inhibiting cyclo-oxygenase) and AA 861 (inhibiting lipoxygenase). These results show that the PAF-induced response of adenylyl cyclase activity in antigen-challenged AM is achieved by its modulation of intracellular arachidonic acid metabolism.
Beusenberg
F D
FD
Department of Pharmacology, Faculty of Medicine, Erasmus University, Rotterdam, The Netherlands.
van Schaik
A
A
van Amsterdam
J G
JG
Bonta
I L
IL
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D016227:Benzoquinones / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004224:Diterpenes; D015777:Eicosanoids / Q000502:physiology*; D046934:Ginkgolides; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D008084:Lipoxygenase; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases
D016227:Benzoquinones; D016861:Cyclooxygenase Inhibitors; D004224:Diterpenes; D015777:Eicosanoids; D046934:Ginkgolides; D007783:Lactones; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; C045856:ginkgolide B; D000242:Cyclic AMP; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D000262:Adenylyl Cyclases; D007213:Indomethacin