title: Capsaicin inhibits calmodulin-mediated oxidative burst in rat macrophages.
abstract: In this study we seek to elucidate the interaction of capsaicin with the calmodulin mediated signal pathways in macrophages, by comparing its action on macrophage functions with a known calmodulin antagonist, fluphenazine. Kinetics of capsaicin uptake by macrophages (10(3) cells) revealed that a maximum of 200 microM capsaicin was taken up within 10 min. Ca2+ ionophore triggered generation of superoxide anion and hydrogen peroxide by macrophages was inhibited in a dose-dependent manner by fluphenazine (IC50, 20 microM and 12 microM, respectively) and also by capsaicin (IC50, 30 microM and 9 microM, respectively), suggesting an involvement of calmodulin in the regulation of NADPH oxidase. In vitro both fluphenazine and capsaicin inhibited Ca2(+)-Mg2+ ATPase and cAMP-phosphodiesterase from macrophages and this inhibition was reversed by exogenous addition of calmodulin. Fluorescence studies revealed a direct Ca2+ dependent interaction of capsaicin with calmodulin. From these results we suggest that capsaicin acts via calmodulin to inhibit stimulus-induced macrophage oxidative burst and also that calmodulin regulates the oxidative burst in macrophages.
authors.affiliation: Department of Biochemistry, University of Mysore, Manasagangothri, India.
authors.forename: G
authors.initials: G
authors.lastname: Savitha
authors.forename: S
authors.initials: S
authors.lastname: Panchanathan
authors.forename: B P
authors.initials: BP
authors.lastname: Salimath
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002211:Capsaicin / Q000378:metabolism / Q000494:pharmacology*; D005476:Fluphenazine / Q000494:pharmacology; D005609:Free Radicals; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
chemical_list: D002147:Calmodulin; D005609:Free Radicals; D007476:Ionophores; D013481:Superoxides; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D002211:Capsaicin; D005476:Fluphenazine