Mechanism involved in the mobilization of neutrophil calcium by 5-hydroxyeicosatetraenoate.
5-Hydroxyeicosatetraenoate (5-HETE), like leukotriene B4 and platelet-activating factor, stimulated human polymorphonuclear neutrophils to mobilize intracellular calcium. The three compounds acted through mechanisms that were inhibited by pertussis toxin, cholera toxin, and PMA. Each agonist, furthermore, desensitized (or down-regulated) the neutrophil's calcium mobilization response to a second challenge with the same agonist. However, 5-HETE and leukotriene B4 had little or no activity in cross-desensitizing neutrophil responses to each other or to platelet-activating factor. Furthermore, 5-HETE interfered minimally or not at all with the binding of radiolabeled leukotriene B4 and platelet-activating factor to their respective receptors on neutrophils. Thus, 5-HETE mobilizes neutrophil calcium by a mechanism different from those used by leukotriene B4 and platelet-activating factor. This mechanism appears to involve specific 5-HETE receptors that couple to pertussis toxin-inhibitable, GTP-binding proteins.
O'Flaherty
J T
JT
Department of Medicine, Wake Forest University Medical Center, Winston-Salem, NC 27103.
Jacobson
D
D
Redman
J
J
D002118:Calcium / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D010972:Platelet Activating Factor / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000032:analysis / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin / Q000032:analysis / Q000187:drug effects; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D006893:Hydroxyeicosatetraenoic Acids; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin; D010566:Virulence Factors, Bordetella; C039351:platelet activating factor receptor; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D002772:Cholera Toxin; D037342:Pertussis Toxin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium