| Project/Area Number |
59440085
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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 |
医学一般
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| Research Institution | Institute of Applied Biochemistry, Univ. of Tsukuba |
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Principal Investigator |
MUNEKATA Eisuke Inst. of Applied Biochem., Univ. of Tsukuba, Assocate Professor, 応用生物化学系, 助教授 (60072766)
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| Co-Investigator(Kenkyū-buntansha) |
KANAZAWA Ichiro Inst. of Clinical Medicine, Univ. of Tsukuba, Associate Professor, 臨床医学系, 助教授 (30110498)
OHTSUKA Masanori School of Medicine, Tokyo medical and dental Univ. Professor, 医学部, 教授 (60013801)
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥29,000,000 (Direct Cost: ¥29,000,000)
Fiscal Year 1986: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1985: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1984: ¥15,000,000 (Direct Cost: ¥15,000,000)
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| Keywords | Neurokinin A / Neurokinin B / Active-conformation / Structure-Activity / relationships / Tachykinin-receptor / 神経伝達ペプチド / 構造と活性の相関 / 平滑筋収縮 / 受容体 |
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| Research Abstract |
Neurokinin A (NKA) and B (NKB) are novel neuropeptides isolated from the acetone-HCI extracts of porcine spinal cord by my research group in 1983. Neurokinin peptides are closely related chemically as well as pharmacologically to so-called tachykinin peptides such as substance P, eledoisin, physaelamin and kassinin. The facts that NKA and NKB exhibit qualitatively the same pharmacological and electro-physiological properties with SP,
Neurokinin A (NKA) His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met- <NH_2>
Neurokinin B (NKB) Asp-Met-His-Asp-Phe-Phe-Val-Gly-Leu-Met- <NH_2>
Substance P (SP) Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met- <NH_2>
suggest that NKA and NKB possess nearly the identical actions and play similar neurophysiological roles in the central and peripheral nervous system in mammalian animals like SP.
In this study, diverse peptide analogues of NKA, NKB and other tachykinins are chemically synthesized and the correlations between chemical structure including conformation and pharmacological activities are investigated. Base on the results of the structure-activity studies, we described that both neurokinin peptides bind specifically to SP-E type receptor, main receptor of rat duodenum and deduced active coformations of these peptides on the receptor sites. On the contrary, NKA and NKB showed no specific susceptibility on the guinea pig ileum which is considered to be specific receptor of SP.
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