Effects of halogenated inhalated anesthetics on nitric oxide (NO) signal transduction system.
| Project/Area Number |
06454452
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Jikei University |
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Principal Investigator |
MASAKI Eiji Jikei University School of Medicine, Department of Anesthesiology, Lecture, 医学部, 講師 (40221577)
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| Co-Investigator(Kenkyū-buntansha) |
AMAKI Yoshikiyo Jikei University School of Medicine, Department of Anesthesiology, Professor, 医学部, 教授 (30056767)
MORIYAMA Michiko Jikei University School of Medicine, Department of Anesthesiology, Assistant, 医学部, 助手 (00246448)
KONDOU Tutomu Jikei University School of Medicine, Department of Anesthesiology, Assistant, 医学部, 助手 (90211250)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1994: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | Nitric oxide (NO) / Reduced iron / Halogenated volatile anesthetics / Hemeprotein / Neurotransmitter / 一酸化窒素(NO) / 揮発性吸入麻酔薬 / グアニレートサイクレース(GC) |
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| Research Abstract |
Nitric Oxide (NO) is unique molecule produced by numerous tissues and cells. In CNS,NO acts as a neurotransmitter and mediates excitatory amino acid-stimulation. It is suggested that those action of NO is associated with expression of memory, consciousness and pain. The receptor for NO is enzyme celled guanylate cyclase (GC) which is a reduced iron-containing hemeprotein, catalyzing the synthesis of cGMP.NO activates GC by binding to the reduced iron. Halogenated inhalate volatile anesthetics is also known to interact with hemeprotein like cytochrome P-450 and hemoglobin through the reduced iron. Although many experiments were done to determine the site of action of inhalate volatile anesthetics, it is still unknown. In addtion, several studies indicate that various agents blocking the excitatory amino acid-NO-cGMP pathway have the anesthetic action. Then, we examine the effects of inhalate volatile anrsthetics on NO-stimulated GC activity in rat brain soluble fraction.
The brain solubl
… More
e fraction was made from male Spague-Dawley rats. The incubation were initiated by adding brain soluble fraction with NO solution and satulated volatele anesthetics buffer. NO and anesthetic concentration were monitored with NO monitor and gasclomatoglaphy, respectively. GC activity was determined by measuring c-GMP,the final product of NO-signal trunsduction pathway, by enzymeimmunoassay. No stimulated GC activity at the lebel of as low as 2 X 10^<-9>. One of the main volatile anesthetics, halothane (H) dose-dependently (0.5-2.7mM) inhibited NO-stimulated GC activity. Moreover, GC activity was also inhibited by H without NO stimulation in brain soluble fraction. These results suggest that 1) : H and NO compete the site of activation of GC (probably reduced iron), 2) : bisides the competition with NO,H has other sites to inhibit GC activity.
Further investigation should be needed to explain whether these effects of halothane is associated with the site of action of inhalated volatile anesthetics. Less
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Report
(3 results)
Research Products
(3 results)
