Inhibition of active oxygen generation in guinea-pig neutrophils by biscoclaurine alkaloids.
Effect of biscoclaurine alkaloids, such as cepharanthine, on active oxygen production of neutrophils was investigated. Cepharanthine inhibited both superoxide generation and luminol-dependent chemiluminescence (CL) induced by either formylmethionyl-leucyl-phenylalanine, opsonized zymosan, arachidonic acid or by phorbol myristate acetate. Ca2(+)- and phospholipid-dependent protein kinase (PKC) activity and the phosphorylation of cytoplasmic protein including 47 kDa proteins of neutrophils were also inhibited by cepharanthine; dose dependent inhibition of CL was quite similar to that of PKC. Among various biscoclaurines tested, the inhibitory effect of cepharanthine, tetrandrine and isotetrandrine was strong, but that of berbamine and cycreanine was weak; the inhibitory action of the former on lipid peroxidation and platelet aggregation were also stronger than those of the latter. These and other observations indicated that these alkaloids inhibited the active oxygen generation by way of stabilizing plasma membrane and inhibiting PKC and NADPH oxidase activation.
Matsuno
T
T
Department of Surgery, Okayama University Medical School, Japan.
Orita
K
K
Edashige
K
K
Kobuchi
H
H
Sato
E F
EF
Inouye
B
B
Inoue
M
M
Utsumi
K
K
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D044182:Benzylisoquinolines; D005609:Free Radicals; D006168:Guinea Pigs; D008163:Luminescent Measurements; D008165:Luminol; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D052117:Benzodioxoles
D000470:Alkaloids; D016718:Arachidonic Acid; D001095:Arachidonic Acids; D044182:Benzylisoquinolines; D005609:Free Radicals; D008165:Luminol; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010100:Oxygen; D011494:Protein Kinases; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate; C006947:cepharanthine; D052117:Benzodioxoles