Studies on a Novel Vasoactive Peptide, Endothelin, Derived from Vascular Endothelium.

研究了新型血管收缩肽内皮素-1 （ET-1）和内皮素-3 （ET-3）对平滑肌的影响。用fura-2法测定细胞质Ca^<2+> (Ca^<2+>]cyt)和收缩表明，ET-1诱导大鼠主动脉、颈动脉、猪和犬气管的收缩比豚鼠大肠带绦虫和回肠的收缩更大。在大鼠子宫中，ET-1通过打开黄体期和发情期电压依赖性Ca^<2+>通道增加（Ca^<2+>）cyt，并且在怀孕期间ET-1也激活了Ca^<2+>内流的额外途径。在大鼠主动脉中，由于ET-1引起的（Ca^<2+>）cyt的增加被Ca^<2+>通道阻滞剂抑制，但肌肉收缩仅被部分抑制，连续添加过量的EGTA进一步降低（Ca^<2+>）cyt，肌肉收缩略有下降。这些结果表明，et -1引起的收缩是由于[Ca^<2+>]cyt和Ca^<2+>对收缩元件的敏感性增加。在不含Ca^<2+>的溶液中，ET-1诱导大鼠主动脉中[Ca^<2+>]cyt和IP_3的短暂升高，提示ET-1刺激了Pl的转换。α -毒素皮纤维实验结果表明，ET-1通过激活gtp结合蛋白收缩平滑肌。这些结果表明，不同类型平滑肌的受体分布和对ET-1和ET-3的内在活性是不同的。这些结果还表明，et诱导的收缩取决于[Ca^<2+>]cyt的增加和收缩元件Ca^<2+>的敏化。

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.