The coupling of 5-oxo-eicosanoid receptors to heterotrimeric G proteins.
5-Oxo-eicosatetraenoic acid (5-oxoETE) stimulated human neutrophil (PMN) and eosinophil chemotaxis, PMN hexose uptake, and PMN membrane GTP/GDP exchange. Pertussis toxin (PT), a blocker of heterotrimeric G proteins (GP), completely inhibited these responses, but proved far less effective on the same responses when elicited by leukotriene B4, C5a, FMLP, platelet-activating factor, IL-8, or RANTES chemotactic factors. 5-OxoETE also specifically bound to the membrane preparations that conducted GTP/GDP exchange. This binding was down-regulated by GTPgammaS, but not ADPgammaS, and displaced by 5-oxoETE analogues, but not by leukotriene B4, lipoxin A4, or lipoxin B4. Finally, PMN expressed PT-sensitive GP alphaiota2 and PT-resistant GP alphaq/11- and alpha13-chains; eosinophils expressed only alphai2 and alphaq/11. We conclude that 5-oxoETE activates granulocytes through a unique receptor that couples preferentially to PT-sensitive GP. The strict dependency of this putative receptor on PT-sensitive GP may underlie the limited actions of 5-oxoETE, compared with other CF, and help clarify the complex relations between receptors, GP, cell signals, and cell responses.
O'Flaherty
J T
JT
Department of Medicine, Section on Infectious Diseases, Wake Forest University Medical Center, Winston-Salem, NC 27157, USA. joflaher@wfubmc
Taylor
J S
JS
Kuroki
M
M
D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000097:blood*; D002250:Carbon Radioisotopes; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000097:blood*; D003847:Deoxyglucose / Q000097:blood; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019204:GTP-Binding Proteins / Q000097:blood; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000097:blood; D020962:Heterotrimeric GTP-Binding Proteins / Q000097:blood*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D037342:Pertussis Toxin; D011518:Proto-Oncogene Proteins / Q000097:blood; D018055:Receptors, Eicosanoid / Q000097:blood*; D012995:Solubility; D013462:Sulfur Radioisotopes; D014226:Triazenes / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000276:immunology
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D002630:Chemotactic Factors; D011518:Proto-Oncogene Proteins; D018055:Receptors, Eicosanoid; D013462:Sulfur Radioisotopes; D014226:Triazenes; D010566:Virulence Factors, Bordetella; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C034613:triacsin C; D003847:Deoxyglucose; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; C498015:GNAI2 protein, human; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins