| Project/Area Number |
61440028
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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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 Professor, 医学部, 教授 (60013801)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIOKA Koichi University, Faculty of Medicine Research associate, 医学部, 助手 (00143579)
YANAGISAWA Mitsuhiko University, Faculty of Medicine Lecturer, 医学部, 講師 (90159252)
SAITO Koji University, Faculty of Medicine Associate Professor, 医学部, 助教授 (20002082)
KONISHI Shiro University, Faculty of Medicine Lecturer, 医学部, 講師 (20014277)
MIYATA Yuhei University, Faculty of Medicine Associate Professor, 医学部, 助教授 (00014275)
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| Project Period (FY) |
1986 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 1989: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1988: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1987: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1986: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | isolated spinal cord-tail preparattion / substance P / tachykinin antagonist / acetylcholine / GABA / tachykinin receptor / descending inhibition / serotonin / タキキニン / スパンタイド / 摘出脊髄標本 / substance P / ニューロキニンA / ムスカリン受容体 / SP拮抗薬 / 脊髄 / 伝達物質 / substance P,GABA / P,GABA / SP受容体 / 感覚系神経伝達物質 / P物質 / Spantide / 摘出脊髄-伏在神経標本 / 摘出脊髄-伏在神経-皮膚標本 / 侵害反射電位 / エンケファリン / プロスタグランジン |
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| Research Abstract |
1. An isolated spinal cord-tail preparation of the neonatal rat was developed. Brief pulse application of capsaicin to the tail induced a ventral root depolarization, which was markedly depressed by spantide. Involvement of substance P (SP) and neurokinin A (NKA) in the nociceptive C-fiber reflex was suggested.
2. The pharmacological profile of spantide was studied on motoneurones of the neonatal rat spinal cord in the presence of tetrodotoxin. Spantide competitively antagonized the NKA- and septide-induced depolarization with pA_2 values of 6.5 for both agonists. Spantide also antagonized the depolarizing action of low concentrations 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.
3. Characteristics of tachykinin-induced acetylcholine (ACh) and GABA release from neonatal rat spinal cord were investigated. SP induced a release of ACh, which was depressed by a low Ca^<2+> medium or tetrodotoxin. SP also induced a release of GABA, which by contrast was TTX-resistant and Ca^<2+>-insensitive. These data imply that the mechanisms of the tachykinin-induced ACh and GABA release are different.
4. The monosynaptic reflex (MSR) evoked by electrical stimulation of the quadriceps femoris nerve was inhibited by conditioning stimulation of the saphenous nerve. This inhibition was potentiated by edrophonium and markedly depressed by atropine. These results suggest that cutaneous primary afferents excite cholinergic spinal neurons, which then inhibit the MSR via muscarinic receptors.
5. The transmitter mechanism of a descending inhibition of the MSR was investigated in the neonatal rat isolated spinal cord. Electrical stimulation of the upper thoracic part of the spinal cord caused a prolonged inhibition of MSR. This inhibition was markedly depressed by 5-HT_1 or 5-HT_2 antagonists, suggesting the involvement of serotonergic fibers in the inhibition.
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