DESENSITIZATION OF HUMAN ENDOTHELIN-A RECEPTOR
DESENSITIZATION OF HUMAN ENDOTHELIN-A RECEPTOR
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DOI：
10.1097/00005344-199322008-00005
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发表时间：
1993-01-01
影响因子：
3
通讯作者：
KRIS, RM
中科院分区：
文献类型：
--
作者：
CYR, C;KRIS, RM
G蛋白偶联受体的反应受同源脱敏作用的调节。由于内皮素A受体(ET(A))在血管收缩中起一定作用，因此对内皮素反应性的脱敏和复敏程度进行了研究。根据人ET(A)受体与牛ET(A)受体的相似性，获得了编码人ET(A)受体的cDNA克隆。以非洲爪哇卵母细胞为模型系统分析其脱敏作用。用人神经激肽A(NKA)受体与ET(A)受体进行脱敏比较。注射这两种受体mRNAs的非洲爪哇卵母细胞表现出同源的脱敏作用，但恢复率不同。人NKA受体在5分钟内失敏，20-30分钟后恢复敏感。人类ET(A)受体也在5分钟内脱敏，但有一个长达1.5-2小时的复敏期。这种延长的恢复期是这类受体所特有的，可能有助于调节ET(A)受体介导的一些有害效应。差异脱敏的机制正在利用人类ET(A)受体的基因工程突变体进行研究。
The response of G-protein-coupled receptors is modulated by homologous desensitization. Because endothelin A receptor (ET(A)) plays a part in vasoconstriction, the extent of desensitization and resensitization of endothelin responsiveness was studied. A cDNA clone encoding human ET(A) receptor was isolated based on similarities to bovine endothelin A receptor. Xenopus laevis oocytes injected with cloned mRNA transcripts were used as a model system for analyzing desensitization. Human neurokinin A (NKA) receptor was used for comparison with ET(A) receptor in desensitization experiments. Xenopus laevis oocytes injected with the two receptor mRNAs show homologous desensitization but variable rates of recovery. Human NKA receptors desensitize within 5 min and resensitize after 20-30 min. Human ET(A) receptors also desensitize within 5 min but have a prolonged resensitization period lasting 1.5-2 h. Such a prolonged recovery period is unique to this class of receptors and may serve to regulate some of the deleterious effects mediated by the ET(A) receptor. The mechanism of differential desensitization is being investigated using genetically engineered mutants of human ET(A) receptor.