1992 Fiscal Year Final Research Report Summary
Argininosuccinate as a possible neuromodulator and localization of its metabolizing enzymes
| Project/Area Number |
03807012
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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 |
General medical chemistry
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| Research Institution | Kagoshima University |
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Principal Investigator |
SAHEKI Takeyori Kagoshima Univ. Faculty of Med. Professor, 医学部, 教授 (10056070)
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| Co-Investigator(Kenkyū-buntansha) |
YATA Toshihiko Kagoshima Univ. Faculty of Med. Associate Professor, 医学部, 助教授 (60166527)
NAKAGAWA Shiro Kagoshima Univ. Faculty of Med. Professor, 医学部, 教授 (70073666)
KOBAYASHI Keiko Kagoshima Univ. Faculty of Med. Assistant Professor, 医学部, 講師 (70108869)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Argininosuccinate / Argininosuccinate synthetase / Argininosuccinate lyase / Arginine / Nitric Oxide (NO) / Nerve cells |
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| Research Abstract |
From our previous immunohistochemical study on the localization of argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) in the rat brain, we postulate that argininosuccinate may be a novel neuromodulator. It is because some neuronal cells contain ASS, but not ASL, and some others contain ASL, but not ASS. We showed that the activity ratios of ASS to ASL in various tissues varied from about unity in the liver, kidney and testis to nearly zero in the spleen and skeletal muscle. As the whole brain, the ratio was 0.27, but the each nucleus or brain part shows quite a varied value from 0.78 to 0.06. These results suggest that the two enzymes do not always play a role cooperatively in arginine-synthesizing system. In many tissues and cells, arginine-synthesizing system may play a role in supplying arginine for the synthesis of nitric oxide (NO). In the parasympathetic ganglia located in the pancreas, ASS was found in the nerve cells where NO synthase detected as NADP dehydrogenase was located. On the contrary, ASS and NO synthase were differently localized in the neuronal cells of striatum, again suggesting that ASS might synthesize argininosuccinate for secretion from the cells as a neuromodulator. We found that argininosuccinate decreased the response of isolated cerebellar cells to glutamte even at the concentration of 10-10M, but it did not affect the response of cultured olfactory cells to glutamate and of Langerhans islet cells to glucose. Further extensive works are needed for the establishment of argininosuccinate as a neuromodulator.
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