1996 Fiscal Year Final Research Report Summary
STUDY ON PROSPECTIVE USE FOR DYNORPHIN FRAGMENTS IN THE TREATMENT OF DEMENTIA
| Project/Area Number |
07557303
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
Biological pharmacy
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| Research Institution | MEIJO UNIVERSITY |
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Principal Investigator |
KAMEYAMA Tsutomu MEIJO UNIVERSITY,PHARMACY,PROFESSOR, 薬学部, 教授 (10076698)
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| Co-Investigator(Kenkyū-buntansha) |
ARAKI Hiroaki TAISHO PHARM.CO., PHARM.LAB., SENIOR RES., 主任研究員
SASAKI Yuhsuke TOHOKU OCLL.PHARMACY,BIOCHEM., PROFESSOR, 教授 (70104081)
NABESHIMA Toshitaka NAGOYA UNIVERSITY,MEDICINE,PROFESSOR, 医学部, 教授 (70076751)
HAYASHI Motoharu KYOTO UNIV., PRIMATE RES.INST., PROFESSOR, 霊長鎖類研究所, 教授 (10027500)
FUKUDA Hideomi NIHON UNIVERSITY,PHARMACY,PROFESSOR, 薬学部, 教授 (50080172)
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| Project Period (FY) |
1995 – 1996
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| Keywords | DYNORPHIN DERIVATIVE / KAPPA-OPIOID RECEPTOR / MU-OPIOID RECEPTOR / ANTINOCICEPTIVE EFFECT / MEMORY AND LEARNING / WRITHING / SCOPOLAMINE / CHOLINERGIC NEURONAL SYSTEM |
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| Research Abstract |
We have already reproted that an opioid-peptide, dynorphin A-(1-13), improves impairment of memory an leaming in several models of amnesia. Since a peptide is able to be easily degrated by peptidass in vivo and is hardly translocated through the blood-brain barrier, the aim of the present study was to develop new dynorphin derivatives in order to increase resistance against peptidases and to assess those biological effects in mice, such as antinciceptive and anti-amnesic effects. 1) A dynorphin derivative, S-9 [Tyr-D-Ala-Phe-Leu-ArgPSI (CH_2NH) Arg-NH_2], injected subcutaneously decreased the occurrence of writhing induce by i.p.injection of acetic acid 120 min after, whereas intracerebroventricular injection of S-9 showed same effect during 30 to 60 min after. 2) The antinociceptive effect described above was antagonized by naloxone, an opioid receptor antagonist, but not by nor-binaltorphimine, a selective kappa-receptor antagonist. 3) S-9 did not show any improving effct on scopolamine-induced impairment of memory and learning. 4) S-10 [Tyr-D-Ala-Phe-Leu-PSI (CH_2NH) Arg-Arg-NH_2] did not show any effect descrided above. These results sugest that peripherally administered S-9, a peptidase-resistant dynorphin derivative has antinociceptive effect through mu-opioid receptor in the brain rather than kappa-receptor, and has no anti-amnesic effect which has been shown by dynorphin A-(1-13).
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