1996 Fiscal Year Final Research Report Summary
Development study of preventive and therapeutic drugs for Alzheimertype senile dementia by using biologically active peptides
| Project/Area Number |
07672396
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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 | Meijo University |
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Principal Investigator |
UKAI Makoto Ph.D., Associate Professor Department of Chemical Pharmacology Faculty of Pharmaceutical Sciences Meijo University, 薬学部, 助教授 (80131209)
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| Co-Investigator(Kenkyū-buntansha) |
KAMEYAMA Tsutomu Ph.D., Professor Department of Chemical Pharmacology Faculty of Pharmaceutical S, 薬学部, 教授 (10076698)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Biologically active peptides / Alzheimer's disease / Deltorphin / Galanin / Passive avoidance learning / Opioids / Tachykinins / Spontaneous alternation performance |
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| Research Abstract |
1. Effects of substance P on scopolamine-induced impairment of spontaneous alternation performance
(1) Substance P improved the scopolamine-induced impairment of spontaneous alternation performance.
(2) The improving effects of substance P were antagonized by treatment with the tachykinin NK-1 receptor antagonist WIN62577.
2. Effects of Tyr-D-Arg-Phe-beta-Ala-NH_2 (TAPA) on passive avoidance learning
(1) TAPA inhibited passive avoidance learning.
(2) The impairing effects of TAPA were reversed by treatment with mu-opioid receptor antagonist beta-funaltrexamine.
3. Effects of galanin on passive avoidance learning, elevated plus-maze learning and spontaneous alternation performance
(1) Galanin inhibited passive avoidance learning, although it had no effects on elevated plusmaze learning or spontaneous alternation performance.
4. Effects of systemic administration of dynorphin A-(1-13) on cycloheximide-induced impairment of passive avoidance learning
(1) The intraperitoneal injection of dynorphin A-(1-13) impaired the cycloheximide-induced impairment of passive avoidance learning.
(2) The improving effects of dynorphin A-(1-13) were reversed by treatment with the kappa-opioid receptor antagonist nor-binaltorphimine.
5. Effects of delta-opioid receptor agonists on learning and memory
(1) [D-Pen^2, L-Pen^5] enkephalin and [D-Ala^2] deltorphin II inhibited passive avoidance learning, although they did not affect spontaneous alternation performance or elevated plus-maze learning.
These results suggest that opioid peptides selective for mu-and delta-opioid receptors and galanin evoke anmesia, while substance P and dynorphin possess anti-amnesic effects. Moreover, it is possible that dynorphin is one of the nootropic neuropeptides.
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