Study on a new defense system in higher animals

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In 1996, Natori et al., found L-Dopa-glutathione conjugate as a novel antibacterial substance in a flesh fly injured. This substance produced hydrogen peroxide to sterilized microorganisms, which suggested a new defense system of insects, In this study, we aimed to explore the new defense system in the higher animals. This author et al. previously identified dopamine-glutathione or cysteine conjugate in the rat lung in 1986. From the structural resemblance to Natori's, these conjugates should be a kind of endogenous defense substances. The first aim was syntheses of endogenous or exogenous defense substances in order to examine their physiological role such as antibacterial. During the synthesis, I found sulfurous acid evolved from cysteine. To know the reason why, it was needed to make cysteins-S-sulfonic acid. There were polymers as by products under the synthetic conditions, This kind of polymerization was confirmed to be involved in amyloid precipitations of transthyretin via its cysteine-S-sulfonic acid. Sulfurous acid was assumed to be an etiological substance against the defense system. It was also assumed that hydrogen peroxide produced from catecholamines by monoamine oxidase played a role. As a whole, a general concept was thought out that hydrogen peroxide from catecholamines in the sympathetic nervous system makes a balance of the defense with nitrogen oxide from acetylcholine in the parasympathetic.