| Project/Area Number |
13671626
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | University of Occupational Environmental Health (UOEH) |
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Principal Investigator |
SHIGEMATSU Akio UOEH, The faculty of medicine, professor, 副学長 (30037428)
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| Co-Investigator(Kenkyū-buntansha) |
SAGATA Kenichiro UOEH, The faculty of medicine, instructor, 医学部, 助手 (30331002)
MINAMI Kouichiro UOEH, The faculty of medicine, assistant professor, 医学部, 講師 (70279347)
瓜生 佳代 産業医科大学, 医学部, 助手 (20309975)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | neurosteroid anestheticis / tramadol / alphaxalone / norepinephrine transporter / nicotinic acetylcholine receptor / Xenopus oocytes / adrenal medullary cells / muscarinic receptor / ニコチン性アセチルコリン受容体イオンチャネル / ノルアドレナリントランスポーター / 腎血流 |
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| Research Abstract |
The mode of action of the analgesic tramadol and alphaxalone, a neurosteroid anestheticis not well understood.
We assayed the effect of tramadol and alphaxalone on [^3H]-norepinephrine ([^3H]-NE) uptake and [^3H]-desipramine binding to plasma membranes isolated from bovine adrenal medulla. We also investigated the effects of tramadol and alphaxalone on muscarinic receptors type 1 and 3, using a Xenopus oocyte expression system. Finally, we investigated the effect of tramadol and alphaxalone on catecholamine secretion, nicotine-induced calcium rises and inward currents using a Ca^<2+>-imaging system and the whole-cell patch clamp technique in bovine adrenal chromaffin cells.
(1) Both tramadol and alphaxalone competitively inhibited norepinephrine transporter function at desipramine binding sites.
(2) Both tramadol and alphaxalone at clinically relevant concentrations inhibits m1 and m3 function via QNB-binding sites.
(3) Tramadol and alphaxalone inhibits catecholamine secretion by inhibiting nicotinic acetylcholine receptor functions and suggest that such inhibitory effects could be one of the antinociceptive mechanisms exerted by tramadol.
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