1986 Fiscal Year Final Research Report Summary
Clinical Pharmacology and Experimental Neurochemistry of ACTH
| Project/Area Number |
60570435
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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 |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
MIMAKI Takashi Osaka University Medical School, 医学部, 助手 (40116108)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Toshihiro Shiga University of Medical Science, 教授 (50028388)
TAGAWA Tetsuzo Osaka University Medical School, 医学部, 助手 (00171570)
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| Project Period (FY) |
1985 – 1986
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| Keywords | ACTH;Homovanillic acid / Benzodiazepine receptor / GABA作動性ニューロン / GABA-Transaminase / 髄液中homovanillicacid / カテコラミン / セロトニン含有神経 |
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| Research Abstract |
cerebrospinal fluid levels of homovanillic acid(HVA) and 5-hydroxy indoleacetic acid(5-HIAA) were measured by high-performance liquid chromatography in four children with intractable seizures. Both HVA and 5-HIAA levels in CSF decreased after ACTH-Z therapy.
The effects of ACTH administration on <^3H> -flunitrazepam binding were studied in Sprague-Dawley rat brain. The effects of ACTH injection on resynthesis of GABA transaminase(GABA-T) after systemic administration of gabaculine, irreversible inhibitor of GABA-T, were also investigated in rat brain by enzyme histochemical technique.
ACTH administration(250ug/day, 7 days) produced a significant decrease in benzodiazepine receptor density(Bmax) in rat cerebral cortex with no change in dissociation constants(Kd).
Four hours after gabaculine injection, intense GABA-T activity was detected in neuronal cell bodies and a few dendrites in control rats, whereas much networks of neuronal processes appeared in ACTH treated rats(250ug/day, 5 days). Eighteen hours after gabaculine injection, in addition to the neuronal staining, a few glial cells showed GABA-T activity in the control rats. In comparison with this, many glial cells showed very intense GABA-T activity, which makes difficult to identify the neurons in ACTH treated rats.
These results suggest that ACTH modulates both benzodiazepine receptor binding and GABA metabolism.
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