| Project/Area Number |
03044120
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | University of Shizuoka |
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Principal Investigator |
YANAIHARA Noboru University of Shizuoka, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (80046250)
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| Co-Investigator(Kenkyū-buntansha) |
J.CHRISTOPHE ベルギー, ブラッセル自由大学, 教授
J.C.BROWN カナダ, ブリティッシュコロンビア大学, 教授
B.AMIRANOFF フランス, INSERM, 主任研究員
H.LABURTHE フランス, INSERM, 教授
F.LEMBECK オーストリー, グラツ大学, 教授
B.PERNOW ストックホルム, ランスランドステイング, 院長
T.HOKFELT スエーデン, カロリンスカ研究所, 教授
KUWAHARA Atsukazu National Institute of Physiological Sciences, Research Associate, 助手 (60142890)
MOCHIZUKI Tohru University of Shizuoka, School of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助教授 (00117780)
HOSHINO Minoru University of Shizuoka, Graduate School of Nutritional and Environmenal Sciences, 大学院・生活健康科学研究所, 助教授 (50150058)
YANAIHARA Chizuko Osaka University, School of Medicine, Professor, 医学部, 教授 (00046252)
OTSUKA Masanori Tokyo Dental University, School of Medicine, Professor, 医学部, 教授 (60013801)
CHRISTOPHE Jean Universite Libre de Bruxelles, Professor
AMIRAMOFF Brigitte INSERM in France, Chief Research Associate
LEMBECK Fred University of Gratz, Institute of Pharmacology, Professor
PERNOW Bengt Karolinska Institute, Professor
HOKFELT Tomas Karolinska Institute, Professor
BROWN John C. British Colombia University in Canada, Professor
BROWN J.C. ブリティッシュ, コロンビア大学, 教授
CHRISTOPHE J ブラッセル自由大学, 教授
HOEKFELT T. カロリンスカ研究所, 教授
AMIRANOFF B. INSERM, 主任研究員
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1992: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1991: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Galanin / Substance P / Galanin (1-15) / Receptor / (D-Thr^6,D-Trp^<8,9>)-galanin (1-15)-ol / Galanin (1-15) receptor / Galanin agonist / Galanin antagonist / PACAP / ガラニン・アゴニスト / ガラニン・アンタゴニスト / 合成ペプチド / 化学合成 / ガラニン作用 / 特異抗体 |
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| Research Abstract |
The neuropeptide galanin with 29 amino acid residues has been known to have numerous biological activities, both in the brain and in the periphery. The following studies have been carried out under International Joint study on Design, Synthesis and Analysis of Agonists Antagonists of Galanin.
1) Twenty-three galanin-related peptides were synthesized by solid phase technology or conventional solution method in our laboratory (N.Yanaihara).
2) Effects of human, rat and porcine galanins on 13.9mM glucose-stimulated insulin release were compared on glucose-induced insulin release in isolated rat pancreas.Among them, rat galanin showed the highest inhibition of glucose induced insulin release.
3) Human and rat galanins as well as porcine galanin at 10^<-8>M inhibited GRP(14-27) stimulated gastrin release, respectively. Among them, rat galanin was the weakest in this system.
4) Human and rat galanins as well as porcine galanin at 10^<-6>M suppressed the contractile response of the circular muscl
… More
e in a dose dependent manner, respectively. The galanins including galanin (1-15)-ol showed nearly equipotent inhibitory effect. These results suggest strongly the existence of the active site of galanin for its suppression of neurally-evoked circular muscle contractions in the amino-terminal half of the molecule.
5) Galanins depressed the c-fiber response evoked by saphenous never preparation 0.01muM and higher concentrations (1-3muM) partially inhibited the monosynaptic reflex. Human galanin was the most potent and porcine galanin was the weakest. The amino-terminal fragment, galanin(1-15)-ol showed very weak effects.
6) Both [D-Trp^<8,9>]-galanin (1-15)-ol and [D-Thr^6,D-trp^<8,9>]-galanin (1-15)-ol were found to act as antagonist on glucose-stimulated insulin release in vitro, while galantide, a peptide comprising galanin (1-13) and substance P(5-11), at 10^<-7>M did not show any antagonistic activity in this system. Especially, [D-Thr^6,D-Trp^<8,9>]-galanin (1-15)-ol at 10^<-7>M completely abolished the inhibitory effect of 10^<-9>M rat galanin in the isolated perfused rat pancreas.
7) The existence and widespread distribution of specific [^<125>I] galanin (1-15) fragment binding sites in the rat brain was demonstrated. These binding sites were also present in several areas lacking or having very few [^<125>I] galanin (1-29) binding sites, such as the dorsal hippocampal formation, the neocortex and the neostriatum.
8) Coexistence and interaction of neuropeptides with substance P and other tachykinins, with special reference to galanin were demonstrated.
Because of the importance of galanin and the related peptides in the role of cellular or extracellular regulatory mechanisms and their potential therapeutic value, and understanding of their detailed interactions with the specific receptor would provide useful information for structure-activity study. A variety of approach to this problems have been performed in this international joint study, And Symposium help in November in Shizuoka was really fruitful and successful. Less
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