1-naphthyl N-methyl carbamate effect on intra- and extracellular concentrations of arachidonic acid metabolites, and on the chemiluminescence generation by mouse peritoneal macrophages.
1-Naphthyl N-methyl carbamate (carbaryl), potent carbamate insecticide with anticholinesterase activity, was tested for its ability to affect mouse peritoneal macrophages in particular arachidonic acid (AA) metabolism and oxidative burst. Carbaryl inhibited in a dose-related manner the reactive oxygen intermediate dependent chemiluminescence (CL) induced by opsonized zymosan (OZ), 12-O-tetradecanoyl phorbol-13-acetate (TPA) and calcium ionophore (A23187); this carbamate did not affect CL-mediated by AA. The intracellular and extracellular concentrations of prostaglandins (PGs) and 5-hydroxyeicosatetraenoic (5-HETE) generated in macrophages stimulated with OZ has been investigated for various periods. Carbaryl effect displayed two successive phases on AA metabolism stimulation. In a first phase (up to 2-15 min), carbaryl did not alter the rapid AA metabolite synthesis (total amount of intra- and extracellular metabolites) but it increased intracellular concentration of PGE2, PGA2, PGF2 alpha and decreased 5-HETE intracellular concentration. In a second phase (after 2-15 min), carbaryl inhibited AA metabolite synthesis. The release of cyclooxygenase (CO) and lipoxygenase (LO) metabolites decreased, in particular PGF2 alpha and PGD2 which in addition seemed to be submit to a cellular retention; the inhibition of other metabolite release appeared essentially related to the inhibition of their synthesis since the intracellular amount did not augment. The inhibition by carbaryl of the NADPH-oxidase dependent CL induced by OZ may be related to the alteration of the intra- and extracellular concentrations of AA metabolites.
Forgue
M F
MF
Institut National de la Santé et de la Recherche Médicale, Université Paul Sabatier, Toulouse, France.
Pipy
B
B
Beraud
M
M
Souqual
M C
MC
Combis
J M
JM
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D012721:Carbaryl / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D008163:Luminescent Measurements; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D010529:Peritoneal Cavity / Q000166:cytology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014316:Tritium; D015054:Zymosan / Q000494:pharmacology
D001095:Arachidonic Acids; D014316:Tritium; D016718:Arachidonic Acid; D000001:Calcimycin; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate; D012721:Carbaryl