Characterization of formylmethionyl-leucyl-phenylalanine stimulation of inositol trisphosphate accumulation in rabbit neutrophils.
Inositol trisphosphate (IP3) formed by phospholipase C-mediated breakdown of triphosphoinositide (PIP2) may be a ubiquitous second messenger for a number of Ca2+-mobilizing receptor agonists. Using [3H]inositol-labeled rabbit peritoneal neutrophils, we report that radiolabeled inositol phosphates are generated in response to the chemotactic peptide, formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe). fMet-Leu-Phe-stimulated formation of [3H]IP3 occurs with a rapid time course and a concentration dependence which closely parallels that of stimulated lysosomal enzyme secretion. The synthetic peptide methionyl-leucyl-phenylalanine, which is unable to promote secretion, failed to elevate [3H]IP3 accumulation, and the competitive antagonist t-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe depressed the stimulant action of fMet-Leu-Phe on [3H]IP3 levels and secretion. The Ca2+ ionophore ionomycin, which promotes secretion, was unable to enhance IP3 levels, confirming that polyphosphoinositide hydrolysis is a specific receptor-mediated event that precedes calcium mobilization during neutrophil activation. The ability of leukotriene B4 to also promote a rapid accumulation of [3H]IP3 suggests that there exists in the neutrophil an interaction between phospholipase A2 and C-mediated events. These findings support the hypothesis that IP3 may be a pivotal messenger for signal transfer by Ca2+-mobilizing receptor agonists.
Bradford
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Rubin
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D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D003571:Cytochalasin B / Q000494:pharmacology; D004987:Ethers / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000097:blood*; D015759:Ionomycin; D007700:Kinetics; D007975:Leukotriene B4 / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D013329:Structure-Activity Relationship; D013403:Sugar Phosphates / Q000097:blood*
D004987:Ethers; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D015117:5,8,11,14-Eicosatetraynoic Acid; D007975:Leukotriene B4; D003571:Cytochalasin B; D015759:Ionomycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015544:Inositol 1,4,5-Trisphosphate