Bioactions of 5-hydroxyicosatetraenoate and its interaction with platelet-activating factor.
In a variety of stimulated cells, platelet-activating factor (PAF) and numerous arachidonate derivatives are co-products that form as a consequence of receptor-mediated phospholipid mobilization. These lipid co-products produce a plethora of biological effects in a wide variety of cell systems. Furthermore, they often have a fascinating although less widely appreciated, interaction. 5-HETE, at submicromolar concentrations, exerts relatively few direct bioactions. It does, however, potently (16-160 nM) raise cytosolic free calcium [Ca2+]i and augment PAF-induced responses in human polymorphonuclear neutrophils (PMN) by as much as 100- to 1000-fold. 5-HETE acts on PMN by a structurally specific, stereospecific and pertussis toxin-inhibitable mechanism. In addition, PMN exposed to 5-HETE exhibit homologous but not heterologous desensitization. These findings suggest that 5-HETE, like PAF, may bind to its own specific plasmalemmal receptors to exert its unique set of bioactions. However, further investigation is required to demonstrate any putative 5-HETE receptors. Other potential mechanisms of 5-HETE-induced bioactions together with the possible effects of 5-HETE on PAF transduction mechanisms are also discussed.
Rossi
A G
AG
Department of Medicine, Wake Forest University Medical Center, Winston-Salem, NC 27103.
O'Flaherty
J T
JT
D000818:Animals; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism* / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology
D006893:Hydroxyeicosatetraenoic Acids; D010972:Platelet Activating Factor; D011956:Receptors, Cell Surface; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid