1997 Fiscal Year Final Research Report Summary
Molecular interaction between general anesthetics and GABAA receptor
| Project/Area Number |
08457407
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Osaka University |
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Principal Investigator |
YOSHIYA Ikuto Osaka University Medical School, Professor, 医学部, 教授 (80028505)
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| Co-Investigator(Kenkyū-buntansha) |
UCHIDA Ichiro Osaka University Medical School, Assistant Professor, 医学部, 助手 (00232843)
NISHIMURA Shinya Osaka University Medical School, Assistant Professor, 医学部, 助手 (00263286)
TAKENOSHITA Makoto Osaka University Medical School, Lecturer, 医学部, 講師 (00144486)
MASIMO Takashi Osaka University Medical School, Associate Professor, 医学部, 助教授 (60157188)
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| Project Period (FY) |
1996 – 1997
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| Keywords | GABA^A receptor / Anesthetic / Subunit / Molecular biology / Mutation / Electrophysiology |
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| Research Abstract |
During the two years period supported this grant, we revealed the following two points by using the molecular biological and electrophysiological methods.
1) By using the chimeric receptor studies between alpha1 and beta3 subunit of GABAA receptor, The site of action of propofol potentiation in GABAA receptor function may be in the long hydrophilic NH2 terminal of alpha1 subunit. The further mutational study of amino residues in alpha1 subunit may be necessary to elucidate the precise site for propofol site.
2) The point mutation of tyrosine to phenylalanine at position 157 in beta2 subunit of GABA receptor drastically decreased the sensitivity to GABA but not anesthetics such as propofol, etomidate and pentobarbital. Also this tyrosine mutation of beta2 subunit had no influence on the modulatory actions of these anesthetics. The result suggested the distinct site of action on the direct action of GABA receptor by GABA and anesthetics and the modulatory action of anesthetics may be not mediated by GABA site.
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