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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Growth Hormone-releasing Hormone As An Agonist Of The Ghrelin Receptor Ghs-r1a
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Growth Hormone-releasing Hormone As An Agonist Of The Ghrelin Receptor Ghs-r1a

机译：生长激素释放激素作为Ghrelin受体Ghs-r1a的激动剂

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摘要

Ghrelin synergizes with growth hormone-releasing hormone (GHRH) to potentiate growth hormone (GH) response through a mechanism not yet fully characterized. This study was conducted to analyze the role of GHRH as a potential ligand of the ghrelin receptor, GHS-R1a. The results show that hGHRH(1-29)NH_2 (GHRH) induces a dose-dependent calcium mobilization in HEK 293 cells stably transfected with GHS-R1a an effect not observed in wild-type HEK 293 cells. This calcium rise is also observed using the. GHRH receptor agonists JI-34 and JI-36. Radioligand binding and cross-linking studies revealed that calcium response to GHRH is mediated by the ghrelin receptor GHS-R1a. GHRH activates the signaling route of inositol phosphate and potentiates the maximal response to ghrelin measured in inositol phosphate turnover. The presence of GHRH increases the binding capacity of ~(125)l-ghrelin in a dose dependent-fashion showing a positive binding cooperativ-ity. In addition, confocal microscopy in CHO cells transfected with GHS-R1a tagged with enhanced green fluorescent protein shows that GHRH activates the GHS-R1a endocytosis. Furthermore, the selective GHRH-R antagonists, JV-1-42 and JMR-132, act also as antagonists of the ghrelin receptor GHS-R1a. Our findings suggest that GHRH interacts with ghrelin receptor GHS-R1a, and, in consequence, modifies the ghrelin-associated intracellular signaling pathway. This interaction may represent a form of regulation, which could play a putative role in the physiology of GH regulation and appetite control.
机译：Ghrelin通过尚未完全表征的机制与生长激素释放激素（GHRH）协同作用，以增强生长激素（GH）响应。进行这项研究以分析GHRH作为ghrelin受体GHS-R1a潜在配体的作用。结果表明，hGHRH（1-29）NH_2（GHRH）在稳定转染了GHS-R1a的HEK 293细胞中诱导了剂量依赖性钙动员，这在野生型HEK 293细胞中未观察到。使用还会观察到钙的升高。 GHRH受体激动剂JI-34和JI-36。放射性配体结合和交联研究表明，对生长激素释放激素的钙反应是由生长素释放肽受体GHS-R1a介导的。 GHRH激活了肌醇磷酸的信号传导途径，并增强了在肌醇磷酸转换中测得的对生长素释放肽的最大反应。 GHRH的存在以剂量依赖性的方式增加了〜（125）1-ghrelin的结合能力，显示出积极的结合合作性。此外，共焦显微镜检查转染了带有增强的绿色荧光蛋白的GHS-R1a的CHO细胞中，表明GHRH激活了GHS-R1a的胞吞作用。此外，选择性GHRH-R拮抗剂JV-1-42和JMR-132还充当了生长素释放肽受体GHS-R1a的拮抗剂。我们的发现表明，GHRH与Ghrelin受体GHS-R1a相互作用，并因此修饰了Ghrelin相关的细胞内信号通路。这种相互作用可能代表一种调节形式，可能在GH调节和食欲控制的生理过程中发挥推定作用。

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