Neurochemical and neurophysiological mechanism for guanidino compoundinduced seizures
| Project/Area Number |
58440081
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
医学一般(含病院管理学・看護学・人類遺伝学・病態検査学・実験動物)
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| Research Institution | Okayama University |
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Principal Investigator |
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| Project Period (FY) |
1983 – 1985
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| Project Status |
Completed (Fiscal Year 1985)
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| Budget Amount *help |
¥15,700,000 (Direct Cost: ¥15,700,000)
Fiscal Year 1985: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1984: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1983: ¥12,700,000 (Direct Cost: ¥12,700,000)
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| Keywords | guanidino compound / El mouse / methylguanidine / <alpha> -guanidinoglutaric acid / 2-guanidinoethanol / homoarginine / <delta> -guanidinoglutaric acid / けいれん発現機構 |
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| Research Abstract |
We have reported that guanidino compound, e.g. taurocyamine, guanidinoacetic acid, <gamma> -guanidinobutyric acid, N-acetylarginine, methylguanidine, and <alpha> -guanidinoglutaric acid(GGA), induced violent convulsions after intracisternal injection into rabbits, dogs, cats, and rats. The summary of the present studies is as follows:
1. Increased levels of methylguanidine were observed in the cerebral cortex, cerebellum, midbrain, and medulla oblongata of El mice with a convulsive disposition. N-Acetylaspartic acid induced in the brain during convulsions.
2. Increased levels of <gamma> -guanidinoacetic acid were observed in the rabbit CSF during pentylenetetrazol induced convulsions.
3. GGA induced seizures were associated with an abnormal serotonergic function, i.e. the transitorily decreased level and facilitated release of 5-HT in the brain.
4. Homoarginine and <alpha> -guanidinovaleric acid induced seizure discharges in rats, when administered topically or intracisternally. <alpha> -guanidinovaleric acid may act on a GABA system to induce spike discharges as an antagonist.
5. Taurocyamine has bipolar effects on convulsions; i.e. it delayed markedly the dibenzoylguanidine-induced convulsions in mice. On the other hand, it increased the incidence of convulsion in the non-stimulated El-mice.
6. A new guanidino compound, <alpha> -guanidinoethanol, was found in normal human urine. It induced epileptic EEG discharges and convulsions when administerd into the rat brain.
7. Incoporation of a <^(15)N> into guanidinoacetic acid in the brain and kidney, and guanidinoacetic acid, methylguanidine and guanidinosuccinic acid in the liver, was observed with a <^(15)N> -analyser after the administration of L-(amidino- <^(15)N> -arginine into mice.
8. A high level of taurocyamine was found in the CSF of epileptic patients. Higher levels of taurocyamine, methylguanidine and N-acetylarginine were demonstrated in the epileptogenic focus tissue of human epileptic patients.
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Research Products
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