Phospholipid metabolism, calcium flux, and the receptor-mediated induction of chemotaxis in rabbit neutrophils.
Rabbit neutrophils were stimulated with the chemotactic peptide fMet-Leu-Phe in the presence of the methyltransferase inhibitors homocysteine (HCYS) and 3-deazaadenosine (3-DZA). HCYS and 3-DZA inhibited chemotaxis, phospholipid methylation, and protein carboxymethylation in a dose-dependent manner. The chemotactic peptide-stimulated release of [14C]arachidonic acid previously incorporated into phospholipid was also partially blocked by the methyltransferase inhibitors. Stimulation by fMet-Leu-Phe or the calcium ionophore A23187 caused release of arachidonic acid but not of previously incorporated [14C]-labeled linoleic, oleic, or stearic acids. Unlike the arachidonic acid release caused by fMet-Leu-Phe, release stimulated by the ionophore could not be inhibited by HCYS and 3-DZA, suggesting that the release was caused by a different mechanism or by stimulating a step after methylation in the pathway from receptor activation to arachidonic acid release. Extracellular calcium was required for arachidonic acid release, and methyltransferase inhibitors were found to partially inhibit chemotactic peptide-stimulated calcium influx. These results suggest that methylation pathways may be associated with the chemotactic peptide receptor stimulation of calcium influx and activation of a phospholipase A2 specific for cleaving arachidonic acid from phospholipids.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology; D009239:N-Formylmethionine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000502:physiology; D044042:Receptors, Formyl Peptide; D014372:Tubercidin / Q000494:pharmacology
D001095:Arachidonic Acids; D005227:Fatty Acids; D009842:Oligopeptides; D010743:Phospholipids; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; C018258:3-deazaadenosine; D006710:Homocysteine; D016718:Arachidonic Acid; D000001:Calcimycin; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D014372:Tubercidin; D002118:Calcium