|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1998 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1997 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 1996 : ¥600,000 (Direct Cost : ¥600,000)
Alterations in mRNA levels, protein content and enzyme activity for nitric oxide synthase (NOS) in the cerebrum and cerebellum during a continuous exposure of neurotoxic metal, methylmercury, were examined in Wistar rats. Subcutaneous (sc) administration of methylmercuric chloride (MMC, 10 mg/kg/day, 8 days) resulted in significant increases with time of NOS activities in the cerebrum (1.6-1.9-fold, 5-8 days) and cerebellum (1.4-fold, 8 days). RT-PCR and immuno-blot analyses indicated that the increase in the enzyme activity caused by this metal appears to be due to increase in protein levels of neuronal NOS (nNOS), but not inducible NOS (iNOS) because little appreciable mRNA and protein for iNOS were seen during MMC exposure. The direct effect of mercuric compounds on nNOS activity in vitro was evaluated using 20,000 g supernatant from rat cerebellum homogenate. In contrast to the in vivo observation, however, inorganic-, alkyl-, and aryl-mercuric compound showed potent inhibition of nNOS activity with IC50 values of 11-43 muM whereas dimethylmercury (DMM) was without effect on the enzyme activity. Further experiments indicated that the inhibition of nNOS by organomercurial occurred via thiol modification.