Endothelin receptors are modulated in association with endogenous fluctuations in estrogen.
Endothelin receptors are modulated in association with endogenous fluctuations in estrogen.
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内皮素受体的调节与雌激素的内源性波动有关。
DOI：
10.1152/ajpheart.1996.271.5.h1999
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Miller,VM
中科院分区：
文献类型：
--
作者：
Barber,DA;Sieck,GC;Fitzpatrick,LA;Miller,VM
实验旨在确定内源性类固醇激素的内源性生理波动是否会影响内皮素受体的表达或功能反应。来自性成熟的雄性、雌性和去卵巢的猪的冠状动脉被准备用于受体结合或器官腔内等长力的测量。在所有的猪中，125I标记的ET-1的竞争结合对于含有未标记的ET-1的单位点模型和含有未标记的ET-3和沙拉福毒素S6c的双位点模型是显著的。所有内皮素配体的结合位点总数在公猪和母猪之间没有差异。在内源性雌激素水平较高的母猪制备的膜中，内皮素-3和沙拉福毒素S6c的高亲和力结合部位的结合亲和力显著增大(抑制常数降低)。在器官腔实验中，雌性猪冠状动脉环对内皮素-1的收缩明显大于雄性猪，而对内皮素-3和沙拉福毒素S6c的收缩作用不明显。去内皮或用消炎痛(10(-5)m ol/L)或消炎痛和NG-单甲基-L-精氨酸(10(-4)m o l/L)处理冠脉环对其无明显影响。这些结果表明，雌激素的内源性波动与雌性猪冠状动脉平滑肌高亲和力内皮素受体亲和力的增加有关。此外，与内源性雌激素状态无关，与公猪相比，雌性猪的冠状动脉对内皮素-1的收缩明显更大。这种现象发生在平滑肌水平，并不依赖于内皮，也不依赖一氧化氮或前列腺素的合成。
Experiments were designed to determine whether endogenous physiological fluctuations in sex steroid hormones affect expression or functional responses of endothelin receptors. Coronary arteries from sexually mature male, female, and ovariectomized pigs were prepared either for receptor binding or measurement of isometric force in organ chambers. Competitive binding of 125I-labeled endothelin-1 was significant for a one-site model with unlabeled endothelin-1 and a two-site model with unlabeled endothelin-3 and sarafotoxin S6c in all pigs. The total number of binding sites for all endothelin ligands was not different between male and female pigs. Binding affinities for the high-affinity binding site for both endothelin-3 and sarafotoxin S6c were significantly greater (lower inhibition constant) in membranes prepared from female pigs with high endogenous estrogen. In organ chamber experiments, contractions to endothelin-1 but not endothelin-3 or sarafotoxin S6c were significantly greater in coronary arterial rings from female compared with male pigs and were not affected significantly by removal of the endothelium or by treatment of the rings with either indomethacin (10(-5) mol/l) or the combination of indomethacin and NG-monomethyl-L-arginine (10(-4) mol/l). These results suggest endogenous fluctuations in estrogen are associated with an increase in affinity of a high-affinity endothelin receptor in coronary arterial smooth muscle of female pigs. In addition, independent of endogenous estrogen status, coronary arteries from female pigs generate significantly greater contractions to endothelin-1 compared with male pigs. This phenomenon occurs at the level of smooth muscle and is not dependent on the endothelium or synthesis of nitric oxide or prostaglandins.