1990 Fiscal Year Final Research Report Summary
Studies on a Novel Vasoactive Peptide, Endothelin, Derived from Vascular Endothelium.
| Project/Area Number |
01480102
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
基礎獣医学
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| Research Institution | University of Tokyo |
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Principal Investigator |
SATO Koichi Univ. Tokyo, Fac. of Agric., Assistant Prof., 農学部, 助手 (90205914)
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| Co-Investigator(Kenkyū-buntansha) |
KARAKI Hideaki Univ. Tokyo, Fac. of Agric., Professor., 農学部, 教授 (60011912)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Smooth muscle / Endothelin / Protein Kinase C / G-protein / Cytosolic Ca^<2+> / Pl-turnover |
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| Research Abstract |
Effects of novel vasoconstrictor peptides, endothelin-1 (ET-1) and-3 (ET-3), on various smooth muscle were examined. Measurement of cytosolic Ca^<2+> (Ca^<2+>]cyt) and contraction using fura-2 method showed that ET-1 induced greater contractions in rat aorta, carotid artery, swine and canine trachea than in guinea pig taenia coli and ileum. In rat uterus, it was appeared that ET-1 increased (Ca^<2+>)cyt through the opening of voltage dependent Ca^<2+> channel in luteal phase and estral phase and additional pathway for Ca^<2+> influx is also activated by ET-1 during pregnancy. In rat aorta, the increase in (Ca^<2+>)cyt due to ET-1 was inhibited by Ca^<2+>-channel blockers although muscle contraction was only partially inhibited and the sequential addition of excess EGTA further decreased (Ca^<2+>)cyt with a small decrease in the muscle contraction. These results suggested that ET-1-induced contraction was due to the increase in [Ca^<2+>]cyt and Ca^<2+> sensitivity of contractile element. In Ca^<2+>-free solution, ET-1 induced the transient increase in [Ca^<2+>]cyt and IP_3 in rat aorta suggesting that ET-1 stimulated Pl turnover. The result of the experiment using alpha-toxin-skinned fiber indicated that ET-1 contracted the smooth muscle through the activation of GTP-binding protein.
These results suggest that the distribution of receptors and the intrinsic activity to ET-1 and ET-3 were different in various types of smooth muscle. These results also suggest that ET-induced contraction was depend on the increment in [Ca^<2+>]cyt and the Ca^<2+> sensitization of the contractile elements.
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