Effects of Diethyldithiocarbamate on Superoxide and Nitric Oxide Production by Neutrophils

We investigated the effect of DDC on nitric oxide (NO) production by neutrophils and activating mechanism of neutrophils. The results were as follows: (1) DDC at high concentration inhibited both nitric oxide (NO) and nitrite (NO_2) Production by rat neutrophils. This decrease may induce O_2^- accumulation. (2) DDC stimulated Or Production by neutrophils in a dose-dependent manner. (3) DDC inhibited myeloperoxidase (MPO) activity of neutrophils in a dose-dependent manner. (4) The O_2^- release by DDC decreased by pertussis toxin, protein kinase C inhibitor, myosin light chain kinase inhibitor, calmodulin antagonist, EGTA and diltiazem. From these results, it is suggested that DDC may induce gastric mucosal damage by stimulating O_2^- release from neutrophils via receptor-mediated process and by inhibition of NO generation. Moreover, protein kinase C and calcium ion may play important roles in this stimulating process.

Diethydithiocarbamate

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nitric oxide

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