Elucidation of the receptor mechanisms involved in the actions of anesthetics using DNA decoy as a transcription inhibitor.
| Project/Area Number |
15390474
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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 |
KAMIBAYASHI Takahiko Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (10273640)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Yukio Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (60294063)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2005: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2004: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2003: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | brain nucleus / inhibition of transcription / analgesia / adrenergic receptor / dexmedetomidine / epinephrine-arrhythmias / I receptor / diabetes mellitus / デコイ型核酸 / siRNA |
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| Research Abstract |
1. Modification of the effects of dexmedetomidine by DNA decoy.
After confirming the anti-arrhythmic and hypnotic effects of a novel alpha2 adrenergic agonist dexmedetomidine administered into locus coeruleus of rats, we tried to elucidate the responsible subtype of alpha2 adrenergic receptor to the effects of dexmedetomidine. We administered DNA decoys, which was designed to inhibit the transcription of DNAs coding alpha2 adrenergic receptor subtypes, into locus coeruleus of rats, and then evaluated the effects of dexmedetomidine. As a result, compared with control group, each DNA decoy did not have statistically significant effects on the anti-arrhythmic and hypnotic property of dexmedetomidine. Each DNA decoy showed the tendency of reducing targeted mRNA in locus coeruleus, but the effect did not reach statistical significance. These results suggest that the direct injection of DNA decoy into locus coeruleus is not effective enough to inhibit the transcription of targeted mRNA, and s
… More
ome modification is needed to improve the efficacy of gene silencing.
2. Anti-arrhythmic effect of imidazoline receptor agonists
Adrenergic agonists which have imidazoline ring in their structure are known to activate I receptors. We examined anti-arrhythmic effects of various alpha2 adrenergic agonists with different affinity to I receptors, and found that I1 receptor, an I receptor subtype, plays a significant role in the anti-arrhythmic effect of alpha2 adrenergic agents. The result suggests that we should take I receptor mechanisms into consideration in order to clarify the receptor mechanisms involved in the anti-arrhythmic effect of dexmedetomidine.
3. Epinephrine-arrhythmias and diabetes mellitus
To elucidate the receptor mechanisms of the enhancement of epinephrine-induced arrhythmia by diabetes mellitus, we examined the effects of various bioactive substances on arrhythmogenic doses of epinephrine in diabetic rats. As a result, we found that ion channel mechanisms play a critical role in the enhancement of epinephrine-induced arrhythmias in diabetic animals. Less
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Report
(4 results)
Research Products
(3 results)
