Tsai Ching-Chung, Li Yi-Chen, Chang Li-Ching, Huang Shih-Che
Department of Pediatrics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
School of Medicine, I-Shou University, Kaohsiung, Taiwan.
Front Pharmacol. 2025 Jul 7;16:1578913. doi: 10.3389/fphar.2025.1578913. eCollection 2025.
Ischemic heart disease (IHD) remains a leading cause of global morbidity and mortality, necessitating the search for novel therapeutic approaches. Recent studies have identified bitter taste receptors (TAS2Rs) in vascular smooth muscle cells as potential therapeutic targets because of their vasorelaxant properties. This study investigated the vasorelaxant effects of TAS2R agonists on porcine coronary arteries and explored their potential as novel therapeutic targets for IHD.
Isolated porcine coronary artery rings were precontracted using U46619 and treated with TAS2R agonists, including flufenamic acid, dapsone, phenanthroline, chloroquine, and quinine. Vasorelaxation induced by TAS2R agonists was quantitatively assessed, and pharmacological inhibitors were used to elucidate the underlying mechanisms of vasorelaxation. Real-time PCR analysis was conducted to confirm the expression of specific TAS2R subtypes in porcine coronary arterial tissue.
TAS2R agonists induced concentration-dependent vasorelaxation, with flufenamic acid showing potent effects, exhibiting an EC50 of 30.4 μM, whereas phenanthroline and chloroquine exhibited moderate responses. In contrast, quinine and dapsone showed mild relaxation. The flufenamic acid-induced effect was attenuated by NG-nitro-L-arginine (47.4% ± 3.04%), apamin (49.2% ± 3.7%), and glibenclamide (49.6% ± 1.5%), indicating the involvement of nitric oxide signaling and potassium channels. PCR analysis revealed the differential expression of TAS2R subtypes, with TAS2R42 showing the highest expression, followed by subtypes 40, 10, and 38.
This study showed that TAS2R agonists, especially flufenamic acid, phenanthroline, and chloroquine, induced vasorelaxation in isolated porcine coronary arteries. The vasorelaxation mechanism of flufenamic acid may involve nitric oxide signaling and potassium channels. The expression of specific TAS2R subtypes, together with functional observations, suggest that bitter taste receptors play a role in coronary vascular regulation, warranting further investigation into their therapeutic potential.
缺血性心脏病（IHD）仍然是全球发病和死亡的主要原因，因此需要寻找新的治疗方法。最近的研究已将血管平滑肌细胞中的苦味受体（TAS2Rs）确定为潜在的治疗靶点，因为它们具有血管舒张特性。本研究调查了TAS2R激动剂对猪冠状动脉的血管舒张作用，并探讨了它们作为IHD新治疗靶点的潜力。
使用U46619使分离的猪冠状动脉环预先收缩，并用TAS2R激动剂进行处理，包括氟芬那酸、氨苯砜、菲咯啉、氯喹和奎宁。对TAS2R激动剂诱导的血管舒张进行定量评估，并使用药理抑制剂阐明血管舒张的潜在机制。进行实时PCR分析以确认猪冠状动脉组织中特定TAS2R亚型的表达。
TAS2R激动剂诱导浓度依赖性血管舒张，氟芬那酸显示出强效作用，其半数有效浓度（EC50）为30.4 μM，而菲咯啉和氯喹表现出中等反应。相比之下，奎宁和氨苯砜显示出轻微的舒张作用。NG-硝基-L-精氨酸（47.4% ± 3.04%）、蜂毒明肽（49.2% ± 3.7%）和格列本脲（49.6% ± 1.5%）减弱了氟芬那酸诱导的作用，表明一氧化氮信号传导和钾通道参与其中。PCR分析揭示了TAS2R亚型的差异表达，其中TAS2R42表达最高，其次是40、10和38亚型。
本研究表明，TAS2R激动剂，尤其是氟芬那酸、菲咯啉和氯喹，可诱导分离的猪冠状动脉血管舒张。氟芬那酸的血管舒张机制可能涉及一氧化氮信号传导和钾通道。特定TAS2R亚型的表达以及功能观察结果表明，苦味受体在冠状动脉调节中起作用，值得进一步研究其治疗潜力。
