| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1989: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
Helodermin is a 35 amino acid peptide isolated originally from the venom of Gila monster. The amino acid sequence of its N-terminal portion shows a high degree of homology with VIP In 1989 I have examined the effect of helodermin (Hd) on vascular physiology in anesthetized dogs using a synthetic Hd and Hd related peptides such as Hd (1-33) -NH_2, Hd (1-31) -NH_2, Hd (1-30) -NH_2 and Hd (1-28) -NH_2 synthesized in this project. Intraarterial infusion of Hd (1-33) -NH_2 and Hd (1-31) -NH_2 caused a dose-dependent elevation in femoral blood flow and the effect lasted significantly longer than that of VIP, in a manner similar to that of Hd itself. On the other hand, Hd (1-30) -NH_2 and Hd (1-28) -NH_2 retained substantial activity, but the prolongation effect was absent. Based on the secondary structures of the analogues predicted by Chou-Fasman method, a high incidence of beta-turn structure in the carboxy terminal 28-35 sequence of Hd appear essential for the prolongation effect on vascular physiology. Based on this result I have synthesized new Hd related peptides such as [Gly^5]-VIP (1-11) -Hd (12-31) -NH_2, VIP (1-11)-Hd (12-31) -NH_2 and VIP (1-11) -Hd (15-31) -NH_2. The vasodilatory activity of new peptides were 5-10 times less potent than that of Hd but the mean half life of them was similar to that of Hd. In addition, infusion of Hd with [Gly^5]-VIP (1-11) -Hd (12-31) -NH_2 caused a significant decrease in the activity of Hd, while infusion of VIP with the same analogue resulted in a increased vasodilatory effect. The present result suggested that VIP and Hd may act on different receptors. In 1990 I was examined the distribution of IR-Hd in porcine tissues using Hd (7-35) specific RIA system. IR-Hd detected in brain and gut. In hypothalamus, medulla oblongata, cerebellum, duodenum, ileum and cacum high concentrate IR-Hd was detected and a gel filtration study showed that the IR-Hd is multi-molecular form.
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