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Clinical Pharmacology and Experimental Neurochemistry of ACTH

Research Project

Project/Area Number 60570435
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionOsaka University

Principal Investigator

MIMAKI Takashi  Osaka University Medical School, 医学部, 助手 (40116108)

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)
Project Period (FY) 1985 – 1986
Project Status Completed (Fiscal Year 1986)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1986: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1985: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsACTH;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
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.

Report

(1 results)
  • 1986 Final Research Report Summary

URL: 

Published: 1987-03-31   Modified: 2016-04-21  

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