Receptor-mediated action of hepoxilin A3 releases diacylglycerol and arachidonic acid from human neutrophils.
We have previously shown that hepoxilin A3 increases the intracellular concentration of Ca+2 in human neutrophils. Herein we address the initial events of hepoxilin action on the neutrophil which precede the rise in intracellular calcium. We show that hepoxilin A3 at 10-1000 nM concentrations releases from [1-14C]-arachidonic acid labeled neutrophils diacylglycerol and unesterified arachidonic acid in a time and concentration dependent fashion. The release of arachidonic acid and diacyglycerol are receptor-mediated events which are blocked by pertussis toxin. This data shows that hepoxilin A3 stimulates phospholipases C and A2 in the cell which may be involved in the rise in cytosolic calcium. Thus, hepoxilins may represent a hitherto unrecognised class of cellular mediators.
Nigam
S
S
Department of Gynaecological Endocrinology, Klinikum Steglitz, Free University of Berlin, FRG.
Nodes
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Cichon
G
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Corey
E J
EJ
Pace-Asciak
C R
CR
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001095:Arachidonic Acids / Q000097:blood*; D002118:Calcium / Q000097:blood; D004075:Diglycerides / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D010712:Phosphatidic Acids / Q000097:blood; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001095:Arachidonic Acids; D004075:Diglycerides; D010712:Phosphatidic Acids; D011956:Receptors, Cell Surface; D010566:Virulence Factors, Bordetella; C038243:8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid; D037342:Pertussis Toxin; D015126:8,11,14-Eicosatrienoic Acid; D002118:Calcium