Grant-in-Aid for international Scientific Research
|Allocation Type||Single-year Grants|
|Research Institution||University of Shizuoka|
YANAIHARA Noboru University of Shizuoka, 薬学部, 教授 (80046250)
ROSSELIN G. INSERM U55, INSERM, 教授
TREGEAR G.w. The University of Melbourne, メルボルン大学, 教授
WEI S.g. Zhejiang Academy of Medicin, 浙江省医学科学院, 教授
LABURTHE H. INSERM U239, INSERM, 教授
BROWN J.c. University of British Columbia, ブリティッシュコロンビア大学, 教授
CHRISTOPHE J. Universite Libre de Bruxelles, 自由大学, 教授
GARDNER J.d. Saint Louis University, セントルイス大学, 教授
CHEY W.y. University of Rochester, ロチェスター大学, 教授
KUWAHARA Atukazu National Institute for Physiological Sciences, 生理学研究所, 助手 (60142890)
MOCHIZUKI Tohru University of Shizuoka, 薬学部, 助教授 (00117780)
HOSHINO Minoru University of Shizuoka, 大学院生活健康科学研究科, 助教授 (50150058)
YANAIHARA Chizuko Osaka University, 医学部, 教授 (00046252)
|Project Period (FY)
Completed(Fiscal Year 1994)
|Budget Amount *help
¥3,800,000 (Direct Cost : ¥3,800,000)
Fiscal Year 1994 : ¥3,800,000 (Direct Cost : ¥3,800,000)
|Keywords||Secretin precursor / CCK receptor / PACAP / Galanin / [D-Trp^8] galanin (1-15) ol / Chinese herb / Helodermin / VIP|
A number of regulatory peptides have been isolated from natural sources and sequenced. In addition, recent advances in the field of gene technology have resulted in a burst of determination about the molecular structure of the peptide precursors. Based on the known information about precursor and mature peptide structures, certain purpose-designed synthetic peptides have enabled the investigation of such questions as the molecular basis of receptor binding and the active roles of peptides. Synthetic replicates of regulatory peptides and their analogs and peptide fragments derived from their precursors provide us with important immunogens for producting region-specific antibodies. The recent discovery of novel regulatory peptides such as PACAP (Pituitary Adenylate Cyclase Activating Peptides) and galanin allows a new perception of the control and physiology of neuronal operation. We need to advance our knowledge by studying the structure of their receptors ligand binding site, coupling
sites with effecter mechanisms, phosphorylation, desensitization, receptors coupled to G-protein or ionic channel.
The purpose of this study was to examine the role of neuropeptide receptor and its antagonist.
The following results were obtained in the present study.
1.We have synthesized several peptides related to human secretin precursor. The potency of synthetic peptides was compared in both rats and dogs by determining volume flow of the pancreas.
Big secretin (secretin-41) was about 1/3 of the potency of porcine secretin-27. Secretin-41 was also used as immunogen to produce anti-big secretin serum to use as a tool for determining brain secretin (Chey, Mochizuki, Yanaihara).
2.We gave tested various PACAP fragments in an attempt to find selective PACAP antagonists. Results showed that both PACAP (5-38) and PACAP (10-38) act as potent antagonists on the receptor-binding, increase of [Ca^<2+>] i and VIP release stimulated by PACAP-38. Both antagonists specifically recognized PACAP receptor (Rosselin, Christophe, Laburthe, Yanaihara).
3.On the other hand, PACAP (1-15) was found to antagonize partially PACAP-evoked chloride secretion in isolated guinea-pig distal colon, and PACAP (1-15) did not block the guinea pig VIP-evoked response (Kuwahara).
4.[D-Trp^8] galanin (1-15) ol was shown to act as a potent agonist on the specific galanin receptor. The present observation suggests that [D-Trp^8] galanin (1-15) ol may be a key compound to develop a novel galanin antagonist.
5.We have examined the effect of extracts of Chinese herb on CCK receptor. Among the extracts examined, lower molecular weight fractions of Saiko extracts were shown to bind the CCK-B receptor. The results showed that Saiko extracts may contain CCK agonist or antagonist (Gardner, Brown, Wei, Yanaihara).
The present demonstration showed clearly the importance synthetic peptide fragments to investigate the role of neuropeptide receptor and its antagonists. Less