1989 Fiscal Year Final Research Report Summary
Molecular biological study on modulatory effects of psychotropic agents on biosynthesis and metabolism of neuropeptides
| Project/Area Number |
62570140
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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 |
Pathological medical chemistry
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| Research Institution | Tokyo Institute of Psychiatry |
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Principal Investigator |
YOSHIKAWA Kazuaki PRIT, Dept. of Molecular Biology, Chief, 分子生物学研究室, 副参事研究員 (30094452)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Akihiro PRIT, Dept. of Molecular Biology, Researcher, 分子生物学研究室, 研究員
AIZAWA Takako PRIT, Dept. of Molecular Biology, Researcher, 分子生物学研究室, 研究員
KAMETANI Fuyuki PRIT, Dept. of Molecular Biology, Researcher, 分子生物学研究室, 研究員 (70186013)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Cholecystokinin / Enkephalin / Gene expression / Protein kinase A / Protein kinase C / Glucocorticoids / Second messenger systems / Psychotropic agents |
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| Research Abstract |
Various kinds of psychotropic agents exert their modulatory effects on neuronal functions through intracellular second messenger systems (e.g., protein kinases A and C). On the other hand, neuropeptides (i.e., endogenous, modulators of neuronal functions) are synthesized through the gene expression of their precursors. In this research project, we have attempted to examine modulatory roles of the second messenger systems in the gene expression of neuropeptide precursors. Major findings obtained are as follows:
1) In the rat telencephalon, the preprocholecystokinin gene expression is increased at early stages of postnatal development. In addition, there is a distinct sex-related difference in the gene expression, presumably due to effect of gonadal steroid hormones.
2) The expression of preproenkephalin gene in rat primary cultured cells is controlled by the activators for protein kinase A and C systems.
3) Glucocorticoids (i.e., steroid hormones having neurotropic actions) potentiate,the preproenkephalin gene activation mediated by protein kinase A system, but not that mediated by protein kinase C system.
4) The preproenkephalin gene is highly expressed in the rat germ cells, and the expression is hardly controlled by the protein kinase systems. The messenger RNA expressed in the germ cells shows a unique structure.
Above findings indicate that the expression of preproenkephalin gene is controlled by the interactions between intracellular second messenger systems. Gene expression of other neuropeptides may be controlled by similar mechanisms, and further studies should thus be planned.
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