| Project/Area Number |
02454133
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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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) |
SUZUKI Hidenori Tokyo Medical & Dental University, Faculty of Medicine Research Associate, 医学部, 助手 (30221328)
MURAKOSHI Takayuki Tokyo Medical & Dental University, Faculty of Medicine Research Associate, 医学部, 助手 (60190906)
YOSHIOKA Koichi Tokyo Medical & Dental University, Faculty of Medicine Associate Professor, 医学部, 助教授 (00143579)
YANAGISAWA Mitsuhiko Tokyo Medical & Dental University, Faculty of Medicine Lecturer, 医学部, 講師 (90159252)
SAITO Koji Tokyo Medical & Dental University, Faculty of Medicine Associate Professor, 医学部, 助教授 (20002082)
石突 正文 東京医科歯科大学, 医学部, 講師 (60114732)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | isolated spinal cord preparation / tachykinins / HPLC / acetylcholine / GABA / tachykinin receptor / Descending inhibition / serotonin / 不活性化機構 / ペプチダーゼ阻害薬 / C線維応答 / 痛覚伝達 / 単シナプス反射 / アデノシン / アデノシンアンタゴニスト / セロトニンアンタゴニスト / アデノシンデアミナ-ゼ / 下降性抑制 / タキキニン受容体 / スパンタイド |
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| Research Abstract |
1. Transmitter mechanisms of a long-lasting inhibition of the monosynaptic reflex (MSR) induced by stimulation of the descending pathway was investigated in the isolated spinal cord of the neonatal rat. The descending inhibition was markedly potentiated by a 5-hydroxytryptamine (5-HT) uptake blocker and was blocked by a 5-HT antagonist, suggesting the involvement of 5-HT in this inhibition.
2. Subtypes of adenosine receptors that mediate the inhibition of MSR was characterized in the spinal cord. Adenosine and the related agonists inhibited the MSR with little change in the DC potential of the ventral root. Rank order of potency of the agonists and the pA_2 values of the antagonists were consistent with the involvement of A_1 receptors in the adenosine-evoked inhibition of MSR.
3. The mechanisms of a cutaneous nerve-evoked inhibition of MSR were studied in the spinal cord-peripheral nerve preparation. Conditioning stimulation of the saphenous nerve evoked an inhibition of the MSR. This inhibition was potentiated by an anticholinesterase and almost completely blocked by atropine. From the effects of muscarinic agonists and antagonists, it was suggested that the receptors involved in the inhibition of MSR are of M_2 type.
4. A possible mechanism of inactivation of tachykinins released from nerve terminals is enzymatic degradation. To investigate this possibility, effect of peptidase inhibitors on C-fiber evoked responses was examined using an isolated spinal cord-saphenous nerve preparation of the newborn rat. A slow depolarization of the L3 ventral root evoked by the saphenous nerve stimulation was enhanced by application of a mixture of peptidase inhibitors in the presence of naloxone. This result suggests that enzymatic degradation plays a physiological role in termination of neurotransmitter action of tachykinins.
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