title: Mechanism of polymorphonuclear leukocyte activation by myristate. Involvement of calcium ion and protein kinase C.
abstract: The stimulative effects of myristate on the superoxide generation and depolarization of membrane potential of polymorphonuclear leukocytes (PMN) are particularly strong, yet myristate does not affect the intracellular free Ca2+ level ([Ca2+]i) in the presence of 1 microM free calcium in calcium-EGTA buffer. The half maximum concentration of myristate was 10 microM. Myristate inhibited the transitory changes in [Ca2+]i induced by formylmethionyl-leucyl-phenylalanine (FMLP), but stimulated further the FMLP-induced superoxide generation; these effects are similar to those of phorbol myristate acetate (PMA). The myristate-induced superoxide generation was partially inhibited by H-7, a specific inhibitor of protein kinase C. Myristate stimulated the activity of Ca2+- and phospholipid-dependent protein kinase (protein kinase C) in a concentration-dependent manner in the presence of 10(-6) M Ca2+. The Ka was 100 microM. These results suggested that there is no relation between the superoxide generation and the [Ca2+]i change in PMNs and that the effects of myristate are similar to those of PMA against PMN.
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D001921:Brain / Q000201:enzymology; D002118:Calcium / Q000097:blood* / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D002784:Cholesterol; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008081:Liposomes; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010713:Phosphatidylcholines; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013481:Superoxides / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D008081:Liposomes; D010713:Phosphatidylcholines; D013481:Superoxides; D002784:Cholesterol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium