| Project/Area Number |
62870010
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Tokyo Medical & Dental University |
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Principal Investigator |
OTSUKA Masanori Tokyo Medical & Dental University, Faculty of Medicine Professor, 医学部, 教授 (60013801)
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| Co-Investigator(Kenkyū-buntansha) |
YANAIHARA Noboru University of Shizuoka, School of Pharmaceutical Science Professor, 薬学部, 教授 (80046250)
MURAKOSHI Takayuki Tokyo Medical & Dental University, Faculty of Medicine Research Associate, 医学部, 助手 (60190906)
YANAGISAWA Mitsuhiko Tokyo Medical & Dental University, Faculty of Medicine Lecturer, 医学部, 講師 (90159252)
MIYATA Yuhei Tokyo Medical & Dental University, Faculty of Medicine Associate Professor, 医学部, 助教授 (00014275)
SAITO Koji Tokyo Medical & Dental University, Faculty of Medicine Associate Professor, 医学部, 助教授 (20002082)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 1989: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1988: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1987: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | Isolated spinal cord preparation / substance P / tachykinin antagonist / neurokinin A / morphine / tachykinin receptor / isolated spinal cord-nerve-skin preparation / non-opioid analgesic / スパンタイド / C線維応答 / 内因性ペプチド / アセチルコリン / GABA / ニューロキニンA / セプタイド / NKー1型受容体 / 脊髄運動ニューロン |
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| Research Abstract |
1. An isolated spinal cord-peripheral nerve-skin preparation of the neonatal rat was developed. Brief pulse application of capsaicin to the skin induced a depolarizing response lasting 20-100 s in a lumbar ventral root. This response was markedly depressed by spantide, suggesting that substance P (SP) and neurokinin A (NKA) are involved in the capsaicin-evoked nociceptive response.
2. In an isolated spinal cord-peripheral nerve preparation of the neonatal rat, electrical stimulation of the saphenous nerve caused a slowly depolarizing ventral root potential (v.r.p.). This slow v.r.p. was depressed by spantide, suggesting the involvement of SP and NKA in the slow v.r.p. The saphenous nerve-evoked slow v.r.p. was depressed by [Met^5] -enkephalin, dynorphin and morphine, and these effects were reversed by naloxone. Galanin, somatostatin and GABA also inhibited the saphenous nerve-evoked slow v.r.p., whereas calcitonin gene-related peptide potentiated the slow v.r.p.
3. The pharmacological profile of spantide was studied on motoneurones of the neonatal rat spinal cord in the presence of tetrodotoxin. NKA and septide induced concentration-dependent depolarizations, which were antagonized by spantide. Analysis of concentration-response curves suggested a competitive antagonism with pA_2 values of 6.5 for both agonists. Spantide antagonized the depolarizing action of low concentrations (0.1-0.3muM) of SP, but rather potentiated that of higher concentrations of SP. These results suggest the existence on rat motoneurons of another class or classes of tachykinin receptors.
4.Screening of non-opioid analgesia In the isolated spinal cord preparation, we found that [D-Arg^1,D-Phe(F)^5,D-Trp^<7,9>, Ala^<11>]SP, which had been newly produced by us, antagonized the SP-evoked ventral root depolarization.
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