A role for guanidino compounds in the brain
Guanidino compounds of guanidinoethanesulfonic acid, guanidinoacetic acid, guanidinosuccinic acid, N-acetylarginine, 3guanidinopropionic acid, creatinine, y-guanidinobutyric acid, arginine, guanidine, methylguanidine, homoarginine and aguanidinoglutaric acid are present in the mammalian brain. These guanidino compounds except for arginine and guanidine induce seizures and convulsions in rat, rabbit and cat by intracisternal injection.
Hirudonine, audonine, a-keto-δ-guanidinovaleric acid, N,N’-dibenzoylguanidine and phenylethylguanidine are also convulsants. Levels of creatinine, guanidinoethanesulfonic acid, creatinine, guanidinoacetic acid and methylguanidine in animal brain were changed at pre-and during convulsions induced by pentylentetrazol, amygdala kindling, iron-induced epileptogenesis and so on. These convulsions are thought to be due to depressed functions of serotonergic neurons and accumulated free radicals.
Arginine is a substrate of nitric oxide production by nitric oxide synthase. a-Guanidinoglutaric acid is a generator of superoxide, hydroxyl radicals and nitric oxide, and induced C6 glial cell death. On the other hand, aminoguanidine is a free radical scavenger. Energy formation by creatine metabolism may inhibit apoptosis induced by pathogenesis. Free radical generation/ reaction and energy generation by guanidino compounds must be important key role in the brain. (Mol Cell Biochem244:5762, 2003)
Key wordsGuanidino compounds brain convulsion free radicals energy generation
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- 1.Jinnai D, Mori A, Mukawa J, Ohkusu H, Hosotani M, Mizuno A: Biochemical and physiological studies on guanidine compounds induced convulsion. Choong Jpn J Brain Physiol 106: 3668–3673, 1969Google Scholar
- 2.Mori A, Hiramatsu M, Takahashi K, Kohsaka M: Guanidino compounds in rat organs. Comp Biochem Physiol 51B: 143–144, 1975Google Scholar
- 3.Nakae I: Synthesis of N,N’-dibenzoylguanidine and its convulsive action. Neurosciences 7: 205–217, 1981Google Scholar
- 4.Shirakabe Y: Synthesis of phenylethylguanidine and its effects on neurotransmitters of mouse brain and electroencephalogram of cat. Neurosciences 8: 161–170, 1982Google Scholar
- 5.Mori A, Hiramatsu M, Numoto A, Robin Y: Action convulsante des derives diguanidiques, l’hirudonine l’arcaine et l’audonine. CR Soc Biol 175: 755–760, 1981Google Scholar
- 7.Mori A, Watanabe Y, Shindo S, Akagi M, Hiramatsu M: a-Guanidinoglutaric acid and epilepsy. In: A. Lowenthal, A. Mori, B. Marescau (eds). Urea Cycle Diseases. Plenum Press, New York, 1983, pp 465–470Google Scholar
- 9.Hiramatsu C: Guanidino compounds in mouse brain II. Guanidino corn-pound levels in brain in relation to convulsions. Okayama Igakkai Zasshi 92: 427–433, 1980 (in Japanese)Google Scholar
- 12.Fukushima M: Guanidino compounds in iron-induced epileptogenic foci of rats. Okayama Igakkai Zasshi 99: 787–806, 1987 (in Japanese)Google Scholar
- 13.Hisayasu Y, Morimoto K, Otsuki S: Increase of methylguanidine and guanidinoacetic acid in the brain of amygdala-kindled rats. Epilepsia 32: 761–766, 1986Google Scholar
- 14.Hiramatsu M, Ohba S, Edamatsu R, Kadowaki D, Mori A: Effect of guanidino compounds on membrane fluidity of rat synaptosomes. In: P.P. Deyn, B. Marescau, V. Stalon, L.A. Qureshi (eds). Guanidino Compounds in Biology and Medicine. John Libbey & Co. Ltd., 1992, pp 387–393Google Scholar
- 15.Hiramatsu M, Niiya-Nishihara H, Mori A: Effect of taurocyamine on taurine and other amino acids in the brain, liver and muscle of mice. Neurosciences 8: 289–294, 1982Google Scholar
- 16.Hiramatsu M, Edamatsu R, Kohno M, Mori A: Scavenging of free radicals by Sho-saiko-to-go-keishi-kashakuyaku-to. In: E. Hosoya, Y. Yamamura (eds). Recent Advances in the Pharmacology of KAMPO Medicines. Excepter Medica, 1988, pp 120–127Google Scholar
- 17.Hiramatsu M, Edamatsu R, Kohno M, Mori A: The reactivity of guanidino compounds with hydroxyl radicals. In: A. Mori, B.D. Cohen, H. Koide (eds). Guanidines. Plenum Press, New York, 1989, pp 97105Google Scholar
- 19.Hiramatsu M, Komatsu M, Kido T: The relationship between reactive oxygen species and the a-guanidinoglutaric acid induced seizure mechanism. In: A. Mori, M. Ishida, J.F. Clark (eds). Guanidino Compounds: 5. Blackwell Science Asia Pty Ltd., 1999, pp 193–198Google Scholar
- 20.Hiramatsu M, Komatsu M: The detection of nitric oxide from aguanidinoglutaric acid by hydroxyl radicals using an electron spin resonance method with spin trap. In: P.P. Deyn, B. Marescau, I.A. Qureshi, A. Mori (eds). Guanidino Compounds. John Libbey & Co. Ltd., 1997, pp 31–36Google Scholar
- 21.Seki S, Yuyama N, Hiramatsu M: Effect of guanidino compounds on hen egg development. In: A. Lowenthal, A. Mori, B. Marescau (eds). Urea Cycle Diseases. Plenum Press, New York, 1983, pp 465–470Google Scholar
- 23.Holtzman D, Kekelize T: Guanidino compounds in studies of brain ATP metabolism. In: A. Mori, M. Ishida, J.F. Clark (eds). Guanidino Compounds: 5. Blackwell Science Asia Pty Ltd., London, 1999 pp 3–15Google Scholar
- 24.Matthew RT, Kaddurah-Daouk R, Beal M: The neuroprotective effect of creatine and its analogs in animal models of neurodegenerative diseases. In: A. Mori, M. Ishida, J.F. Clark (eds). Guanidino Compounds: 5. Blackwell Science Asia Pty Ltd., London, 1999, pp 105–115Google Scholar