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Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
Published on: June 7, 2016
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Targeting GPR39 in structure-based drug discovery reduces Ang II-induced hypertension
Dongxu Hua1,2,3, Wanlin Huang1, Qiyang Xie2,3
1Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China.
Communications Biology
|November 5, 2024
Summary
Ablating G protein-coupled receptor 39 (GPR39) mitigated hypertension by reducing vascular damage. Targeting GPR39 with a small molecule ligand also improved vascular function, offering new therapeutic strategies.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Hypertension Research
Background:
- Endothelium-dependent vascular injury is central to angiotensin II (Ang II)-induced hypertension.
- The role of G protein-coupled receptor 39 (GPR39) in this process remains unclear.
Purpose of the Study:
- To investigate the role and mechanisms of GPR39 in Ang II-induced hypertension.
- To identify and validate potential therapeutic strategies targeting GPR39.
Main Methods:
- GPR39 knockout (KO) mice were subjected to Ang II administration.
- Vascular function, fibrosis, inflammation, oxidative stress, and apoptosis were assessed.
- NOD-like receptor protein 3 (Nlrp3) expression was analyzed.
- Structure-based virtual screening identified a GPR39 ligand (Z1780628919).
Main Results:
- GPR39 expression was elevated in hypertensive models.
- GPR39 ablation ameliorated vascular fibrosis, improved vasodilation, and reduced inflammation, oxidative stress, and apoptosis.
- GPR39 deficiency decreased Nlrp3 expression, and Nlrp3 activation reversed GPR39 KO benefits.
- The GPR39 ligand Z1780628919 demonstrated antihypertensive effects and improved vascular function.
Conclusions:
- GPR39 plays a critical role in Ang II-induced hypertension pathogenesis.
- Downregulation of Nlrp3 by GPR39 inhibition underlies its protective effects.
- GPR39 and its ligand Z1780628919 represent promising therapeutic targets for hypertension.
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