Lu Xinping, Bidaud Isabelle, Ladram Ali, Gershengorn Marvin C
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Endocrinology. 2003 May;144(5):1842-6. doi: 10.1210/en.2002-221074.
Previously, three receptors, xTRHR1, xTRHR2, and xTRHR3, were cloned from brain tissue of Xenopus laevis with primers designed using sequences from the mammalian TRH receptor (TRHR) subtype 1. We expressed the Xenopus receptors in HEK 293EM cells and studied their binding and signaling properties using a series of TRH analogs substituted at the first, second, and third positions. We observed that the three Xenopus receptors exhibited binding and signaling properties that were distinct. Although xTRHR1 was most similar to mouse TRHR1 (mTRHR1), it exhibited binding affinities that were different from mTRHR1. In contrast to mTRHR2, xTRHR2 exhibited lower affinities and potencies for all TRH analogs than mTRHR1. The xTRHR3 displayed very low affinities and potencies for TRH and TRH analogs and showed little discrimination for TRH analogs; it is likely, therefore, that another peptide is the cognate ligand for xTRHR3. Our findings show differences between TRHR1 and TRHR2 from Xenopus and mammals and suggest that xTRHR3 is a receptor for a ligand other than TRH.
此前，利用基于哺乳动物促甲状腺激素释放激素受体（TRHR）亚型1序列设计的引物，从非洲爪蟾的脑组织中克隆出了三种受体，即xTRHR1、xTRHR2和xTRHR3。我们在HEK 293EM细胞中表达了爪蟾受体，并使用一系列在第一、第二和第三位被取代的促甲状腺激素释放激素（TRH）类似物研究了它们的结合和信号特性。我们观察到这三种爪蟾受体表现出不同的结合和信号特性。尽管xTRHR1与小鼠TRHR1（mTRHR1）最为相似，但它表现出与mTRHR1不同的结合亲和力。与mTRHR2相反，xTRHR2对所有TRH类似物的亲和力和效力均低于mTRHR1。xTRHR3对TRH和TRH类似物的亲和力和效力非常低，并且对TRH类似物几乎没有区分能力；因此，很可能另一种肽是xTRHR3的同源配体。我们的研究结果显示了爪蟾和哺乳动物的TRHR1与TRHR2之间的差异，并表明xTRHR3是一种除TRH之外的配体的受体。
