| Project/Area Number |
06807123
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Miyazaki Medical College |
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Principal Investigator |
NAGATA Naoto Miyazaki Medical College, Department of Intensive Care Unit, Lecturer, 医学部, 講師 (90145425)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Osamu Miyazaki Medical College, Department of Surgical Division, Assistant Professor, 医学部, 助手 (20253841)
TAKASAKI Mayumi Miyazaki Medical College, Department of Anesthesiology, Professor, 医学部, 教授 (30094212)
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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 |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Protein Kinase C / Anesthetic Drugs / Protein kinase C / Halothane / Sevofluran / Isoflurane / 吸入麻酔薬 / Protein Kinase C / Sevoflurane |
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| Research Abstract |
This study was made a plan according to the paper (Nature, 364 : 82,1993) which reported that anesthetic drugs suppressed PKC activities in central nervous tissues. We tried at first to establish an in vitro PKC assay system in order to analyze molecular actions of anesthetic drugs. Since differential expressions of PKC subclasses in brain tissues were reported elsewhere, responsibility of PKC subclasses to anesthetic drugs were examined by using a well-established cDNA expression system. Contrary to our estimation, we could not have reproducible results on PKC activities in the first in vitro experiment. We also could not have any PKC suppression by halothane although it was reported that PKC activity in nerve cells was suppressed by halothane. The following factors are considered to possible reasons why our approach failed.
1.Difference in anesthetic drug effects between on in vitro experimental system and on in vivo experimental system :
The report which we first referred to make a pl
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an of this study showed that PKC activity was suppressed in vivo in nervous system equilibrated with anesthetic drugs and the report did not show that the drugs affected directly on PKC activity in nerve cells. It is possible that the results in the report were final effects on an in vivo complex neuron network. The difference between in vivo study and in vitro study may be the reason why no PKC suppression was found in COS7 cell lines which were used for in vitro cDNA expression experiment.
2.Difference between drug sensitivity and/or signal transduction systems which may be specific to cell-lineage and/or species :
Although the anesthetic drugs were reported to suppress PKC activities in nerve cells, the COS7 cell we used in this study is not a nerve cell but a monkey renal cell. Therefore, there could be much difference in cell-lineage and species between rat/human nerve cell and monkey renal cell. This difference might introduce some differential intracellular signaling or drug-sensitivity between two lineages.
From those possibilities described above, we noticed a difficulty in our in vitro approach and then we performed an in vivo approach simultaneously too. Actually PKC activities were examined in brain tissue extracts from the rats which were anesthetized with nembutal, halothane, or sevoflurane. Unlike the previous report, however, we could not find any suppressed PKC activity by halothane in the rat brain tissues. Rat brain PKC activity in our in vivo experiment was enhanced by halothane. On the other hand, sevoflurane suppressed rat PKC activity. Less
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