1992 Fiscal Year Final Research Report Summary
A Study of tachykinin-mediated neural mechanisms in the spinal cord and development of tachykinin antagonists as analgesics and anti-allergic drugs
| Project/Area Number |
02557101
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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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) |
TERAO Shinji Takeda Chemical Industries, Co., Ltd. Director, 創薬研究本部, 部長
SUZUKI Hidenori Tokyo Medical & Dental University, Faculty of Medicine Research Associate, 医学部, 助手 (30221328)
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)
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| Project Period (FY) |
1990 – 1992
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| Keywords | isolated spinal cord preparation / substance P / tachykinin antagonist / acetylcholine / GABA / tachykinin receptor / non-opioid analgesic / アセチルコリン |
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| Research Abstract |
1. An isolated spinal cord-skin preparation of the newborn rat was developed. Brief pulse application of capsaicin to the skin induced a depolarizing response lasting 20-40 s in a lumbar ventral root. This response was markedly depressed by tachykinin antagonists, suggesting that tachykinins are involved in the capsaicin-evoked nociceptive response.
2. Characteristics of neurotransmitter release evoked by tachykinins were examined. Substance P (SP) -evoked GABA release was blocked neither by removal of Ca^<2+> from perfusion medium nor by tetrodotoxin (TTX). These characteristics of the GABA release were similar to those of the SP-evoked histamine release from mast cells. By contrast, the acetylcholine (ACh) release was Ca^<2+> dependent and blocked by TTX. Receptors mediating ACh release were found to have characteristics different from those of classical NK-1, NK-2 and NK-3 tachykinin receptors characterized in the peripheral tissues.
3. Non-peptide tachykinin antagonist candidates were screened by several kinds of assay systems. Although some of them showed high affinities to receptors in the rat brain and IM-9 cell line, they showed no antagonistic effect on the tachykinins-evoked depolarizing responses of the ventral root in the rat spinal cord preparation.
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Research Products
(12 results)
