2002 Fiscal Year Final Research Report Summary
EFFECTS OF ANESTHETICS ON TRANSMISSION IN CNS
| Project/Area Number |
11307049
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
IKEMOTO Yoshimi Kyushu University Faculty of Dental Science, Prof., 歯学研究院, 教授 (90091272)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Shinichi Faculty of Dental Science, Ass. Prof., 歯学研究院, 助手 (00315095)
YOSHIDA Atsuya Faculty of Dental Science, Ass. Prof., 歯学部付属病院, 講師 (00284521)
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| Project Period (FY) |
1999 – 2002
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| Keywords | anesthetics / central neurons / neurontransmission / calcium ion concentration / miniature presynaptic current / histamine / mast cells / methyl paraben |
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| Research Abstract |
It is known that general anesthetics increase the GABA-A response in the CNS, resulting in augmentation of inhibitory transmission. Human recombinant GABA-A receptors were expressed in Sf9 cells and subunit specific effects of isoflurane were found, indicating that volatile anesthetics interact with membrane channel proteins to induce anesthesia in humans.
We dissociated central neurons of the rat, which had presysaptic terminals (boutons) attached. Under voltage clamp of these neurons, miniature EPSCs were recorded. Isoflurane increased the frequency, not amplitude of the glycinergic mIPSC. The increase was observed in both the presence and absence of external calcium ions, suggesting that the calcium concentration in the bouton was increased via release from the intracellular store sites.
ATP acts as an excitatory neurotransmitter via P2X receptors in peripheral and central nervous system. In DRG neurons of the rat, we identified slow and fast decaying ATP currents, which were due to activation of P2X2 and P2X3 receptor subtypes, respectively. Ketamine had no effects on the ATP currents. Propofol reduced the peak amplitude of the fast type current and accelerated the decay of the slow type current in the presence of ATP. Pentobarbital decreased the fast type current more potently than the slow type. The reduction was greater in less acidic environment, suggesting that ionized form of the agent was responsible for the effect.
Methyl paraben is contained as preservative in local anesthetic cartridges for dental use. Methyl paraben increased the intracellular concentration of rat peritoneal mast cells, probably via IP3 production. When PKA was activated somehow, the agent enhanced the release of histamine from the mast cells. This finding suggests that methyl paraben may induce anaphylactoid reactions in clinical practice.
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