Elmoselhi A B, Grover A K
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Mol Cell Biochem. 1997 Nov;176(1-2):29-33.
Endothelin is one of the most potent vasoconstrictors known. It plays an important role in the regulation of vascular tone and in the development of many cardiovascular diseases. This study focuses on the receptor types and the Ca2+ mobilization responsible for endothelin-1 (ET-1) contraction in de-endothelialized pig coronary artery rings. ET-1 contracted the artery rings with an EC50 = 6.5 +/- 1 nM and a maximum contraction which was 98.6 +/- 9% of the contraction produced by 60 mM KCl. BQ123 (5 microM), an ETA antagonist, reversed 78 +/- 3% of the ET-1 contraction (50 nM). IRL1620, a selective ETB agonist, produced 23 +/- 3% of the total ET-1 contraction with an EC50 = 12.7 +/- 2 nM. More than 85% of the contraction due to 100 nM IRL 1620 was inhibited by 200 nMBQ788, an ETB antagonist. Therefore, approximately 80% of the ET-1 contraction in this artery occurred via ETA receptors, and the other 20% was mediated by ETB receptors. To assess the Ca2+ pools utilized during the ET-1 response, ET-1 contraction was also examined in medium containing an L-type Ca2+ channel blocker nitrendipine, and in Ca2+ free medium containing 0.2 mM EGTA. In Ca2+ containing medium the contraction elicited by ET-1 was 98.6 +/- 9% of the KCl contraction, however, in the presence 10 microM nitrendipine the ET-1 induced contraction was 54 +/- 7% of the KCl contraction, and in Ca(2+)-free medium it was 13 +/- 2%. Similarly, the IRL 1620 contractions in Ca2+ containing medium, in the presence of nitrendipine and in Ca(2+)-free medium were 22.4 +/- 3%, 12 +/- 3% and 11 +/- 2% of the KCl response respectively. Thus, both ETA and ETB contractions utilize extracellular Ca2+ pools via L-type Ca2+ channels and other undefined route(s), as well as intracellular Ca2+ pools. In the pig coronary artery smooth muscle, ET-1 contractions occur predominantly via ETA receptors, with ETB receptors using similar Ca2+ mobilization pathways, but the ETB receptors appear to use the intracellular Ca2+ stores to a greater extent.
内皮素是已知最强效的血管收缩剂之一。它在血管张力调节及多种心血管疾病的发展过程中发挥着重要作用。本研究聚焦于去内皮猪冠状动脉环中负责内皮素 -1（ET-1）收缩的受体类型及Ca2+动员情况。ET-1使动脉环收缩，其EC50 = 6.5±1 nM，最大收缩幅度为60 mM KCl所产生收缩的98.6±9%。ETA拮抗剂BQ123（5 μM）使ET-1收缩（50 nM）反转了78±3%。选择性ETB激动剂IRL1620产生的收缩幅度为ET-1总收缩幅度的23±3%，其EC50 = 12.7±2 nM。ETB拮抗剂200 nM BQ788抑制了100 nM IRL 1620引起的超过85%的收缩。因此，该动脉中约80%的ET-1收缩通过ETA受体发生，另外20%由ETB受体介导。为评估ET-1反应过程中所利用的Ca2+池，还在含有L型Ca2+通道阻滞剂尼群地平的培养基以及含有0.2 mM EGTA的无Ca2+培养基中检测了ET-1的收缩情况。在含Ca2+的培养基中，ET-1引起的收缩为KCl收缩的98.6±9%，然而，在存在10 μM尼群地平的情况下，ET-1诱导的收缩为KCl收缩的54±7%，在无Ca2+培养基中则为13±2%。同样，含Ca2+培养基、存在尼群地平的培养基以及无Ca2+培养基中IRL 1620引起的收缩分别为KCl反应的22.4±3%、12±3%和11±2%。因此，ETA和ETB介导的收缩均通过L型Ca2+通道及其他未明确的途径利用细胞外Ca2+池，以及细胞内Ca2+池。在猪冠状动脉平滑肌中，ET-1收缩主要通过ETA受体发生，ETB受体利用类似的Ca2+动员途径，但ETB受体似乎在更大程度上利用细胞内Ca2+储存。
