Inhibition of tyrosine hydroxylase activity by methyl bromide exposure.
Rats were exposed to methyl bromide gas (16-250 ppm) for 8 hr, and tyrosine hydroxylase (TH) activity in the striatum, hypothalamus, frontal cortex, midbrain, and medulla oblongata was measured in brain homogenates from exposed rats, and in vivo following administration of decarboxylase inhibitor. Exposure to methyl bromide dose-dependently inhibited both in vitro and in vivo TH activity. Of the five brain areas, TH activity in the hypothalamus was most sensitive to methyl bromide. The time course of enzyme inhibition after exposure was similar to those of decreases in catecholamine concentrations, locomotor activity change, and body temperature reported previously. These results suggest methyl bromide reduces catecholaminergic neuronal activity in the brain via inhibition of TH activity.
National Institute of Industrial Health, Kanagawa, Japan.
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Honma
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Miyagawa
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Sato
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors*
D006842:Hydrocarbons, Brominated; C005218:methyl bromide; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D009638:Norepinephrine