Enhanced production of platelet-activating factor in stimulated rat leukocytes pretreated with triacsin C, A novel acyl-coA synthetase inhibitor.
Triacsin C, a product of Streptmyces sp. SK-1894, was previously reported as an inhibitor of long chain acyl-CoA synthetase. Pretreatment with triacsin C (500 nM) for 1h enhanced production of platelet-activating factor in rat neutrophils, followed by stimulation with A23187 or fMLP. Amount of lyso-PAF was also augumented. Triacsin C alone did not increase PAF content and did not modulate enzymatic activities of acytransferase, cholinephosphotransferase, acetylhydrolase, acetyltransferase or phospholipase A2. These results suggest that triacsin C might enhance supply of substrate for PAF synthesis, i.e. accumulation of lyso-PAF by interfering reacylation pathway.
Hayashi
M
M
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Imai
Y
Y
Naraba
H
H
Tomoda
H
H
Omura
S
S
Oh-ishi
S
S
D000215:Acylation; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014226:Triazenes / Q000494:pharmacology*; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014226:Triazenes; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; C034613:triacsin C; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase