2004 Fiscal Year Final Research Report Summary
The study of behavioral pharmacology, cellular and molecular biology on big dynorphin-induced painful paresthesia.
| 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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| Keywords | Big dynorphin / Poly-L-lysine / N-Ethylmaleimide / NMDA receptor ion-channel complex / Polyamine recognition site / Intrathecal administration / Prodynorphin knockout mice / Nociceptive behavior |
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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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Research Products
(7 results)
