| Project/Area Number |
61560346
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
基礎獣医学
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| Research Institution | University of Osaka Prefecture, College of Africulture, |
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Principal Investigator |
YAGASAKI Osamu University of Osaka Prefecture, College of Africulture, 農学部, 教授 (90081504)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1987: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1986: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Ethylcholinemustard / Cholinergic nervous system / Acetylcholine release choline uptake / intestinal motility / 腸運動 / デルドリン痙攣 / AF64A / 神経機能障害 / 腦 / 小腸 |
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| Research Abstract |
General toxicity:Rat injected i.p. with AF64A at a dose of 1/3 to 11/25 LD50 (291 umol/kg) showed a transient sign of motor disterbance and long lasting singns of adipsia and aghagia. When rats received AF64A with an initial dose of 86 umol/kg i.p. and nine consecutive daily dose of 12.9 umol/kg, ACh contents in the cerebral cortex, hippocampus and striatum decreased significantly. The decrease was sustained even 10 days after the last injection. ACh release induced by electrical stimulation or high K^+ was significantly reduced. The T-maze spontaneous alternation behavior in the treated rats was also impaired. The levels of other neurotransmitters such as NE, 5-HT and GABA were unchanged. No morphological changes in the brain was detected by light- or electron-microscopic observations.
Neurochemical observations:Administration of choline with AF64A significantly inhibited the development of the signs of the functional deficienty of central cholinergic nervous system in rats. In the AF6
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4A treated rats, ChAT activity in nerve terminals decreased in hippocampus and cortex, while the agent had no direct effect on the extracted soluble ChAT. The brain synaptosomal preparations from AF64A treated rat had the same activity of high affnity choline uptake with that of control. A specific binding of [^3H]nicotine to membrane preparation from cortex increases. These results further support a presynaptic site of aciton for AF64A, and suggest that it may acutely disrupt some processes underlying ACh release.
Applications:In AF64A treated mice, the neurotoxic symptoms evoked by dieldrin were clearly alleviated supporting our previous suggestion that excitatory cholinergic mechanism in CNS may be involved in the neurotoxic symptoms. In another series of experiments, half of intestines form AF64A treated rats failed to produce the relaxations of the circular muscles in the anal part of locally distended wall of the intestine. These results suggest that there exist cholinergic interneurons in the nervous pathways from the mechano-receptors to the smooth muscles.
Conclusion: AF64A is an usuful agent in studying the physiological roles of cholinergic nervous systems. Less
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