AcanthamoebaおよびTetrahymenaのポリアミン合成に対する各種阻害剤の影響

Effects of 9 drugs known as inhibitors of ornithine decarboxylase (ODC), S-adenosyl-methionine decarboxylase (SAMDC), spermidine (Spd) synthase or polyamine oxidase (PO) and some polyamines on polyamine synthesis of the protozoa, Acanthamoeba castellanii and Tetrahymena pyriformis were determined. Cellular polyamines were analyzed by high-perfomance liquid chromatography after culture in the absence or presence of drugs. Effects of the drugs on ODC activity in vitro were also studied. Methylacetylenicputrescine (MAP) and α-difluoromethylornithine (DFMO), at 10-2.5mM, decreased putrescine (Put) levels and inhibited ODC activity. Diaminopropane (Dap) levels in A. castellanii were decreased by MAP or DFMO, suggesting an inhibitory effect on PO activity to produce Dap from Spd. Diaminobutene at the concentration of 1mM markedly decreased Put levels and markedly inhibited ODC activity in vitro. DL-α-Hydrazino-σ-aminovaleric acid (HAVA), at 2.5mM, decreased levels of both Put and Spd. HAVA had an inhibitory effect on ODC and Spd synthase. At 10-5mM, 2-mercaptoethylamine (MEA) and dicyclohexylamine (DCHA) weakly and 3-methyltiopropylamine (MTPA) strongly decreased Spd levels. The great increase in Put levels induced by MTPA suggests enhancement of ODC activity in addition to the inhibition of Spd synthase. Methylglyoxal-bis (guanylhydrazone) (MGBG), at 10-5mM, slightly decreased Spd levels, suggesting inhibition of SAMDC activity as in mammalian cells. Chloroquine preferentially decreased Dap levels in A. castellanii. Chloroquine might be specifically inhibit PO activity in the protozoon. Addition of spermine (Spm) and Dap into the media resulted in a decrease in Spd and Put levels, respectively. It was suggested that Spm suppressed Spd synthesis in both protozoa and that Dap reduced ODC activity in T. pyriformis