| Project/Area Number |
14572062
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tohokn Phaimaceulical University |
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Principal Investigator |
TAN-NO Koichi Tohoku Pharmaceutical University, Pharmacology, Assistant Professor, 薬学部, 講師 (20207260)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Big dynorphin / Poly-L-lysine / N-Ethylmaleimide / NMDA receptor ion-channel complex / Polyamine recognition site / Intrathecal administration / Prodynorphin knockout mice / Nociceptive behavior / ダイノルフィン類 / NMDA受容体複合体 / 疼痛関連行動 / NMDA受容体関連拮抗薬 / マウス / ダイノルフィンA |
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| Research Abstract |
In the present study, the role of spinal dynorphin system in facilitation of nociceptive transmission was examined. The obtained results are as follows:
1.Intrathecal (i.t.) administration of big dynorphin (3 fmol), a prodynorphin-derived peptide consisting dynorphins A and B, to mice produced nociceptive behavior.
2.Poly-L-lysine (12 and 36 pg), the same polycationic peptide as big dynorphin, also produced nociceptive behavior.
3.N-Ethylmaleimide(NEM), an inhibitor of cysteine proteases degrading dynorphins, produced nociceptive behavior.
4.The nociceptive behavior produced by these compounds was inhibited by the antagonists at the polyamine recognition site on the NMDA receptor ion-channel complex.
5.The NEM- and big dynorphin-induced nociceptive behavior was inhibited by pretreatment with dynorphin A- and dynorphin Bantiserum.
6.The NEM-induced nociceptive behavior was not observed in prodynorphin knockout mice.
These results suggest that ii administered big dynorphin and the inhibition of endogenous big dynorphin degradation by NEM produce nociceptive behavior through the activation of the NMDA receptor ion-channel complex by acting on the polyamine recognition site owing to the positive charge of this peptide.
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