Kazu Takeno

Effect of methylmercury on brain acetylcholine concentration and turnover in mice

Effects of methylmercury chloride (MMC) on regional acetylcholine (ACh) concentrations and turnover in the mouse brain were studied and compared with those of 3′-chloro-4-stilbazole (CS) and of hemicholinium-3 (HC-3). A long-term treatment with MMC (5 mg Hg/kg/day) induced nervous signs and decreased ACh in striatum and cerebral cortex, and conversion ratios of [14C]ACh in cerebellum, striatum, and cerebral cortex of mice. A single administration of CS (200 mg/kg) decreased ACh in the cortex and the conversion ratios in the three brain regions. An intracerebral injection of HC-3 (100 μg/kg) also decreased ACh and the conversion ratios in striatum and cortex. It is postulated that ACh concentration and ACh turnover rate in brain of methylmercury-poisoned animals may be reduced.

Changes in cytoplasmic and vesicular acetylcholine content in insect ganglia during tetanic stimulation

Acetylcholine (ACh) content was reduced by about 30 pmol or 20% of the initial ACh content in the cockroach sixth abdominal ganglion in response to prolonged (30 min) tetanic stimulation at 40 Hz of the cercal nerves in the presence of 10−3 M hemicholinium-3 (HC-3). The reduction in ACh content in ganglia occurred in the cytoplasmic rather than the vesicular ACh fraction. The latter showed instead a transient increase followed by a gradual decrease to the previous level. Similar changes in ACh in the fractions were produced also by the stimulation, although the ACh content in ganglia did not change in a calcium-free saline, but was reduced in the presence of 50 μM dantrolene or 1–5 mM cobalt chloride. Synaptic transmission at the cercal nerve-giant nerve fiber synapses rapidly decreased and was abolished within a few minutes during tetanic stimulation at 40 Hz, but recovered on reducing the frequency to 0.1 Hz. The decline in transmission was not affected by HC-3, but a significant delay was observed in the recovery following 30 min of tetanic stimulation in the presence of HC-3. These results may suggest that the depletion of ACh as a functional store occurs in the cytoplasmic ACh fraction, rather than in the vesicular one, after prolonged stimulation in the presence of HC-3. The latter fraction shows and increase in the uptake of cytoplasmic ACh that depend on the presence of intracellular calcium ions during stimulation.