首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Discovery of recently adopted orphan receptors for apelin, urotensin II, and ghrelin identified using novel radioligands and functional role in the human cardiovascular system.
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Discovery of recently adopted orphan receptors for apelin, urotensin II, and ghrelin identified using novel radioligands and functional role in the human cardiovascular system.

机译:发现使用新的放射性配体和在人类心血管系统中的功能作用,鉴定了最近采用的孤儿蛋白,尿素蛋白II和生长素释放肽的孤儿受体。

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摘要

Using novel synthetic radioligands, we have discovered receptors for the recently paired apelin (APJ orphan receptor), ghrelin (GHS orphan receptor), and urotensin II (orphan GPR14) in the human cardiovascular system and determined their anatomical localisation. In addition, we have established functional vasoactive properties for these three peptides as potential vasoconstrictor/vasodilator mediators and provided evidence for alteration of receptor density in cardiovascular disease. We find that receptors for apelin, ghrelin, and urotensin II are widely distributed in human cardiovascular tissue, suggesting perhaps vasoactive roles for these peptides in human vascular physiology and a potential role in pathophysiology. Apelin and urotensin II are potent vasoconstrictors with low efficacy, consistent with their low receptor density. Ghrelin receptor density was increased (approximately three- to fourfold) with atherosclerosis of coronary artery disease and accelerated atherosclerosis of saphenous vein grafts, compared with normal vessels, highlighting a potentially beneficial role for this novel vasodilator peptide in human vascular disease. Our approach has demonstrated one successful strategy for translating genetic information encoding recently paired orphan receptor ligands into discovery of function. This study has the advantage of focussing on the actual disease processes, which allow the more precise identification of novel therapeutic targets.
机译:使用新型的合成放射性配体,我们发现了人类心血管系统中最近配对的apelin(APJ孤儿受体),ghrelin(GHS孤儿受体)和urotensin II(孤儿GPR14)的受体,并确定了它们的解剖定位。此外,我们已经建立了这三种肽的功能性血管活性特性,作为潜在的血管收缩剂/血管扩张剂,并为心血管疾病中受体密度的改变提供了证据。我们发现apelin,ghrelin和urotensin II的受体广泛分布于人类心血管组织中,提示这些肽在人类血管生理中可能具有血管活性作用,并且在病理生理中具有潜在作用。 Apelin和urotensin II是有效的血管收缩药,疗效低,与它们的低受体密度一致。与正常血管相比,冠状动脉疾病的动脉粥样硬化和大隐静脉移植物的动脉粥样硬化加速,Ghrelin受体密度增加(大约三到四倍),突显了这种新型血管扩张肽在人类血管疾病中的潜在有益作用。我们的方法证明了一种成功的策略,可以将编码最近配对的孤儿受体配体的遗传信息转化为功能发现。这项研究的优势是着眼于实际的疾病过程,从而可以更精确地鉴定新的治疗靶标。

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