Karaki H, Sudjarwo S A, Hori M, Sakata K, Urade Y, Takai M, Okada T
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
Eur J Pharmacol. 1993 Feb 16;231(3):371-4. doi: 10.1016/0014-2999(93)90112-u.
In isolated rat aorta, endothelin-1 induced contractions at lower concentrations than endothelin-3. The contractile effects were augmented by removing the endothelium. In contrast, endothelium-1 and endothelin-3 at similar concentrations induced endothelium-dependent relaxation in norepinephrine-stimulated aorta. IRL 1038 ([Cys11,Cys15]endothelin-1(11-21); 3 microM) augmented the contractile effects of endothelins only in the presence of the endothelium. IRL 1038 (0.3-3 microM) inhibited the endothelium-dependent relaxation induced by endothelins but not by carbachol. IRL 1038 itself did not change muscle tension. These results suggest that IRL 1038 is a novel antagonist of the ETB receptor responsible for the release of relaxing factor from the vascular endothelium.
在离体大鼠主动脉中，内皮素-1在比内皮素-3更低的浓度下即可诱导收缩。去除内皮后，收缩效应增强。相反，相似浓度的内皮素-1和内皮素-3在去甲肾上腺素刺激的主动脉中可诱导内皮依赖性舒张。IRL 1038（[Cys11,Cys15]内皮素-1(11-21)；3微摩尔）仅在内皮存在时增强内皮素的收缩效应。IRL 1038（0.3 - 3微摩尔）抑制内皮素诱导的内皮依赖性舒张，但不抑制卡巴胆碱诱导的舒张。IRL 1038本身不改变肌肉张力。这些结果表明，IRL 1038是一种新型的ETB受体拮抗剂，该受体负责从血管内皮释放舒张因子。
