title: Inhibition by islet-activating protein of a chemotactic peptide-induced early breakdown of inositol phospholipids and Ca2+ mobilization in guinea pig neutrophils.
abstract: Receptors for a chemotactic peptide (fMet-Leu-Phe) in guinea pig neutrophils were primarily coupled to phospholipase C catalyzing breakdown of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate, which was in turn responsible for intracellular Ca2+ mobilization. These early responses of neutrophils to fMet-Leu-Phe, eventually leading to O2- generation, were abolished by prior exposure of cells to islet-activating protein (IAP), pertussis toxin, which had been reported to bring about ADP-ribosylation of a membrane Mr = 41,000 protein (Okajima, F., and Ui, M. (1984) J. Biol. Chem. 259, 13863-13871). The IAP substrate, probably the inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase (Ni) or an analogous protein, is hence proposed to mediate fMet-Leu-Phe receptor-linked activation of the phospholipase C. In support of this proposal, A23187 and phorbol myristate acetate which stimulate arachidonate release or O2- generation by-passing these early processes of signaling were effective in IAP-treated cells as well. Release of arachidonic acid and accumulation of inositol 1-monophosphate in delayed response to fMet-Leu-Phe were also abolished by the IAP treatment of cells, despite the fact that slowly-onset inflow of Ca2+ which must be responsible for these delayed responses was observed in these IAP-treated cells. Thus, the IAP substrate may play an additional role in Ca2+-dependent activation of somehow compartmentalized phospholipases.
mesh_terms: D037361:Adenylate Cyclase Toxin; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism*; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: D037361:Adenylate Cyclase Toxin; D001095:Arachidonic Acids; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; C002647:inositol 1-phosphate; D016718:Arachidonic Acid; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium