Functional endothelin/sarafotoxin receptors in rat heart myocytes: structure-activity relationships and receptor subtypes.
Functional endothelin/sarafotoxin receptors in rat heart myocytes: structure-activity relationships and receptor subtypes.
复制标题
大鼠心肌细胞中的功能性内皮素/萨拉福毒素受体：结构-活性关系和受体亚型。
DOI：
10.1016/0006-291x(89)92312-7
复制
发表时间：
1989
影响因子：
3.1
通讯作者：
M. Sokolovsky
中科院分区：
文献类型：
--
作者：
R. Galron;Y. Kloog;A. Bdolah;M. Sokolovsky
使用人和大鼠内皮素（分别为 ET-1 和 ET-3）、SRTX-b 和 SRTX-c，在新生大鼠心肌细胞中表征了内皮素 (ET) 和 sarafotoxin (SRTX) 家族肽的功能受体。完整细胞和匀浆的结合研究表明，ET-1 和 SRTX-b 对这些受体的亲和力明显高于 ET-3 和 SRTX-c。 ET/SRTX 肽的这种结合谱表明它们与指定为 E-Sα 的受体亚型相互作用。所有四种肽均诱导时间和剂量依赖性磷酸肌醇水解，效力顺序如下：ET-1 > SRTX-b > SRTX-c > ET-3。因此，对受体具有中等亲和力的ET-3对此反应的效果最差。这些结果证实并扩展了我们之前的报告，即 ET/SRTX 肽与新表征的与磷酸肌醇代谢和 Ca2+ 动员相关的受体相互作用。磷酸肌醇形成的起始很大程度上独立于细胞外Ca 2+ 、维拉帕米和硝苯地平，表明ET/SRTX肽不是电压依赖性Ca 2+ 通道的激动剂。
Functional receptors for the peptides of the endothelin (ET) and sarafotoxin (SRTX) family were characterized in newborn rat heart myocytes using human and rat endothelins (ET-1 and ET-3, respectively), SRTX-b and SRTX-c. Binding studies in intact cells and homogenates revealed significantly higher affinities of ET-1 and SRTX-b than of ET-3 and SRTX-c towards these receptors. This binding profile ofET/SRTX peptides points to their interaction with the receptor subtype designated E-Sα. All four peptides induced time- and dose-dependent phosphoinositide hydrolysis with the following rank order of potency: ET-1 > SRTX-b > SRTX-c > ET-3. Thus, ET-3 which possesses an intermediate affinity toward the receptor was the least effective with regard to this response. These results confirm and extend our earlier report that theET/SRTX peptides interact with a newly characterized receptor(s) associated with phosphoinositide metabolism and Ca2+mobilization. The initiation of inositol phosphate formation is largely independent of extracellular Ca2+, verapamil and nifedipine, indicating that theET/SRTX peptides are not agonists for the voltage-dependent Ca2+-channels.