Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi-City, Chiba, 274-8510, Japan.
Sci Rep. 2022 Jul 27;12(1):12829. doi: 10.1038/s41598-022-16917-6.
This study was performed to elucidate whether eicosapentaenoic acid (EPA) suppresses spasm-prone blood vessel contractions induced by a thromboxane mimetic (U46619) and prostaglandin F (PGF) and determine whether the primary target of EPA is the prostanoid TP receptor. Accordingly, we assessed: (1) the tension changes in porcine basilar and coronary arteries, and (2) changes in the Fura-2 (an intracellular Ca indicator) fluorescence intensity ratio at 510 nm elicited by 340/380 nm excitation (F340/380) in 293T cells expressing the human TP receptor (TP-293T cells) and those expressing the human prostanoid FP receptor (FP-293T cells). EPA inhibited both porcine basilar and coronary artery contractions induced by U46619 and PGF in a concentration-dependent manner, but it did not affect the contractions induced by 80 mM KCl. EPA also inhibited the increase in F340/380 induced by U46619 and PGF in TP-293T cells. In contrast, EPA showed only a marginal effect on the increase in F340/380 induced by PGF in FP-293T cells. These findings indicate that EPA strongly suppresses the porcine basilar and coronary artery contractions mediated by TP receptor and that inhibition of TP receptors partly underlies the EPA-induced inhibitory effects on these arterial contractions.
本研究旨在阐明二十碳五烯酸 (EPA) 是否抑制血栓烷类似物 (U46619) 和前列腺素 F (PGF) 诱导的易痉挛血管收缩,并确定 EPA 的主要靶标是否为前列腺素 TP 受体。因此,我们评估了:(1) 猪基底动脉和冠状动脉的张力变化,以及 (2) 在表达人 TP 受体 (TP-293T 细胞) 和表达人前列腺素 FP 受体 (FP-293T 细胞) 的 293T 细胞中,由 340/380nm 激发引起的 Fura-2(细胞内 Ca 指示剂)荧光强度比 (F340/380) 的变化,由 U46619 和 PGF 诱导。EPA 以浓度依赖性方式抑制 U46619 和 PGF 诱导的猪基底动脉和冠状动脉收缩,但不影响由 80mM KCl 诱导的收缩。EPA 还抑制了 U46619 和 PGF 诱导的 TP-293T 细胞中 F340/380 的增加。相比之下,EPA 对 PGF 诱导的 FP-293T 细胞中 F340/380 的增加仅显示出轻微的影响。这些发现表明,EPA 强烈抑制由 TP 受体介导的猪基底动脉和冠状动脉收缩,并且抑制 TP 受体部分是 EPA 抑制这些动脉收缩的基础。