Differential inhibition by nedocromil sodium of superoxide generation elicited by platelet activating factor in human neutrophils.
Nedocromil sodium (10(-10) - 10(-9) M) produced a dose-related inhibition of superoxide anion generation induced by platelet activating factor (PAF) in human polymorphonuclear leukocytes (PMNs). At a higher concentration (3 x 10(-7) M), nedocromil sodium significantly inhibited superoxide generation elicited by N-formyl-methionyl-leucylphenylalanine, but was unable to block the response to phorbol dibutyrate. Nedocromil sodium (10(-11) - 10(-5) M) enhanced PAF-stimulated lysozyme release in a non-concentration-dependent manner, and was completely ineffective in depressing PAF-induced release of [3H]arachidonic acid and the rise in cytosolic Ca2+. The preferential inhibitory effects of nedocromil sodium on PAF-induced activation of superoxide generation may provide insight into the therapeutic action of this drug as an anti-asthmatic agent.
Rubin
R P
RP
Department of Pharmacology and Toxicology, Medical College of Virginia, Richmond 23298.
Thompson
R H
RH
Naps
M S
MS
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D002118:Calcium / Q000097:blood; D006801:Humans; D009113:Muramidase / Q000097:blood; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D017835:Nedocromil; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D013481:Superoxides / Q000097:blood*
D001095:Arachidonic Acids; D010972:Platelet Activating Factor; D015363:Quinolones; D017835:Nedocromil; D013481:Superoxides; D016718:Arachidonic Acid; D015240:Phorbol 12,13-Dibutyrate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009113:Muramidase; D002118:Calcium