W-7, a calmodulin antagonist, primes the stimulation of human neutrophil respiratory burst by formyl peptides and platelet-activating factor.
Low concentrations of the calmodulin antagonist W-7 (1-10 microM) enhanced the respiratory burst (RB) of human polymorphonuclear leukocytes (PMN) stimulated by N-formyl-methionyl-leucyl-phenylalanine, whereas high drug concentrations (above 20 microM) depressed it. The maximal increase obtained with 5-10 microM W-7 affected both initial rate (50%) and total superoxide anion production (150%). W-7 also primed both parameters of the RB mediated by platelet-activating factor, although higher drug concentrations were required (15-50 microM). By contrast, W-7 depressed the RB induced by the calcium ionophore A23187 and by a protein kinase C activator, phorbol myristate acetate, with an IC50 of approximately 20 and 8 microM, respectively. These data show the enhancing effect of W-7 on chemoattractant-mediated RB and suggest that RB priming may involve calmodulin-dependent regulation of chemoattractant-mediated early signalling events.
Périanin
A
A
Département de Pharmacologie, CNRS URA 1534 Hôpital Cochin, Paris, France.
Pedruzzi
E
E
Hakim
J
J
D000001:Calcimycin / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D002147:Calmodulin; D010972:Platelet Activating Factor; D013449:Sulfonamides; D013481:Superoxides; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; C017967:W 7