FMLP-induced enzyme release from neutrophils: a role for intracellular calcium.
The ability of the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP) to stimulate beta-glucuronidase release and 45Ca2+ release from rabbit neutrophils was studied. FMLP stimulated enzyme release from cytochalasin B-treated cells either in the presence or the absence of extracellular calcium. Depletion of cell calcium, by exposure to either ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid or the calcium ionophore A23187, blocked the ability of FMLP to stimulate enzyme release and 45Ca2+ release in the absence of extracellular calcium. The ability of A23187 to lower the 45Ca2+ content of neutrophils, to block FMLP-stimulated 45Ca2+ release, and to inhibit FMLP-stimulated enzyme release in the absence of calcium was dose dependent over the same concentration range (10(-8) to 10(-6) M A23187) for all three actions. In contrast, FMLP stimulated enzyme release from A23187-treated cells, provided that extracellular calcium was present. This secretory response was normal as judged by cell ultrastructure and FMLP dose-response relationships. It is concluded that A23187 depletes a pool of intracellular calcium usually released by FMLP and that release of calcium from this pool is necessary for initiation of enzyme secretion in the absence of extracellular calcium.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D005966:Glucuronidase / Q000097:blood / Q000378:metabolism; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives*; D008854:Microscopy, Electron; D009239:N-Formylmethionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D009842:Oligopeptides / Q000494:pharmacology*; D011817:Rabbits
D009842:Oligopeptides; D000001:Calcimycin; D009239:N-Formylmethionine; D004533:Egtazic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008715:Methionine; D005966:Glucuronidase; D002118:Calcium