Evidence for two platelet activating factor receptors on eosinophils: dissociation between PAF-induced intracellular calcium mobilization degranulation and superoxides anion generation in eosinophils.
We have compared platelet activating factor (PAF)-induced eosinophil peroxidase (EPO) release and intracellular calcium mobilization with superoxide anion (.O2-) generation from guinea pig eosinophils. EPO release and Ca2+ mobilization occurred at lower concentrations of PAF (EC50 values of 1.3 nM and 11.5 nM, respectively) while .O2- production was observed at higher concentrations (EC50 of 31.7 microM). Receptor characterization with the competitive PAF antagonist, WEB 2086, gave pA2 values of 8.5 and 8.3 for EPO enzyme release and rise in [Ca2+]i, respectively, and 5.8 for the .O2- production. In addition, PAF-induced degranulation and elevation of [Ca2+]i were dependent on extracellular Ca2+ whereas PAF-stimulated .O2- generation was dependent on the presence of extracellular Mg2+ ions. These results suggest the existence either of two subtypes of the PAF receptor or a single receptor that can exist in one of two affinity states on guinea pig eosinophils.
Kroegel
C
C
Department of Thoracic Medicine, University of London, U.K.
Yukawa
T
T
Westwick
J
J
Barnes
P J
PJ
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002118:Calcium / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006168:Guinea Pigs; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D010544:Peroxidases / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000096:biosynthesis*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles
D001381:Azepines; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014227:Triazines; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; D013481:Superoxides; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D008274:Magnesium; D002118:Calcium