期刊文献+

心力衰竭相关孤儿型G蛋白偶联受体的研究进展

Advances in Orphan G-Protein-Coupled Receptors Associated with Heart Failure
下载PDF
导出
摘要 G蛋白偶联受体是已知的浆膜受体中最大的家族,介导并参与多种细胞外信号的转导。这些包括神经递质、气味和光信号。由于它们广泛表达于人体的各种器官和组织中,可作为治疗各种疾病的药物靶点。其中,一些G蛋白偶联受体的内源性配体尚未被鉴定出来,称为孤儿G蛋白偶联受体。它们具有多种生理功能,具有治疗不同疾病的潜力。心力衰竭是一种由心脏血液循环系统的结构和功能损害引起的全身性疾病。虽然新药物的引进和应用大大降低了心力衰竭的死亡率和再住院率,但它仍然是发病率和死亡率的一个主要原因。因此,迫切需要开发新的药物来改善心力衰竭的症状和预后。近年来,研究发现许多孤儿g蛋白偶联受体可通过不同途径参与心力衰竭的发生发展,作为心力衰竭新的治疗靶点越来越受到关注。在探索GPR22、GPR35、GPR37L1在心力衰竭中的作用时,我们发现了更有效的新药物靶点,并阐明了新的治疗策略。 G-protein-coupled receptors are the largest family of plasma membrane receptors known to mediate and participate in the transduction of a variety of extracellular signals. These include neurotransmitters, odors, and light signals. As they are widely expressed in various organs and tissues of the body, they can be used as drug targets to treat various diseases. Among them, the endogenous ligands of some G-protein-coupled receptors have not been identified and are known as orphan G-protein-coupled receptors. They have a variety of physiological functions and the potential to be used to treat different diseases. Heart failure is a systemic disease caused by the structural and functional impairment of the cardiac blood circulatory system. While the introduction and application of new drugs have significantly reduced the mortality and re-hospitalization rates of heart failure, it remains a major cause of morbidity and mortality. Subsequently, there is an urgent need to develop new drugs to improve the symptoms and prognosis of heart failure. In recent years, studies have found that many orphan G-protein-coupled receptors can participate in the occurrence and development of heart failure through different pathways and have received increasing attention as new therapeutic targets for heart failure. In exploring the role of GPR22, GPR35, GPR37L1 in heart failure, we found more effective new drug targets and shed light on novel strategies for treatment.
作者 袁鑫 刘俊
出处 《临床医学进展》 2022年第3期1789-1794,共6页 Advances in Clinical Medicine
  • 相关文献

参考文献1

二级参考文献89

  • 1Beigi F, Bertucci C, Zhu W, Chakir K, Wainer IW, Xiao RP, et al.Enantioselective separation and online affinity chromatographic characterization of R,R- and S,S-fenoterol. Chirality 2006; 18: 822-7.
  • 2Jozwiak K, Khalid C, Tanga MJ, Berzetei-Gurske I, Jimenez L, Kozocas JA, et al. Comparative molecular field analysis of the binding of the stereo isomers of fenoterol and fenoterol derivatives to the β2 adrenergic receptor. J Med Chem 2007; 50: 2903-15.
  • 3Woo AY, Wang TB, Zeng X, Zhu W, Abernethy DR, Wainer IW, et al. Stereochemistry of an agonist determines coupling preference of 132-adrenoceptor to different G proteins in cardiomyocytes. Mol Pharmacol 2009; 75: 158-65.
  • 4Seifert R, Dove S. Functional selectivity of GPCR ligand stereoisomers: new pharmacological opportunities. Mol Pharmacol 2009; 75: 13-8.
  • 5Jozwiak K, Woo AY, Tanga MJ, Toll L, Jimenez L, Kozocas JA, et al. Comparative molecular field analysis of fenoterol derivatives: A platform towards highly selective and effective β2-adrenergic receptor agonists. Bioorg Med Chem 2010; 18: 728-36.
  • 6Talan MI, Ahmet I, Xiao RP, Lakatta EG. β2AR in the treatment of congestive heart failure: long path to translation. J Mol Cell Cardiol 2011; 51: 529-33.
  • 7Mangmool S, Shukla AK, Rockman HA. I3-Arrestin-dependent activation of Ca^2+/calmodulin kinase II after 131-adrenergic receptor stimulation. J Cell Biol 2010; 189: 573-87.
  • 8Zhu W, Woo AY, Yang D, Cheng H, Crow MT, Xiao RP. Activation of CaMKlloC is a common intermediate of diverse death stimuli-induced heart muscle cell apoptosis. J Biol Chem 2007; 282: 10833-9.
  • 9Ling H, Zhang T, Pereira L, Means CK, Cheng H, Gu y, et al. Requirement for Ca^2+/calmodulin-dependent kinase II in the transition from pressure overload-induced cardiac hypertrophy to heart failure in mice. J Clin Invest 2009; 119: 1230-40.
  • 10Van Oort RJ, McCauley MD, Dixit SS, Pereira L, Yang Y, Respress JL, et al. Ryanodine receptor phosphorylation by calcium/calmodulindependent protein kinase" promotes life-threatening ventricular arrhythmias in mice with heart failure. Circulation 2010; 122: 2669- 79.

共引文献27

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部