Nakamoto Kazuo, Tokuyama Shogo
Department of Clinical Pharmacy, Kobe Gakuin University, School of Pharmaceutical Sciences, 1-1-3 Minatojima, Chuo-ku, Kobe, 650-8586 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2012 Aug;32(4):233-7.
The important functional role of fatty acids in both onset and suppression of pain has become increasingly apparent in recent years. Recently, we have also demonstrated that the release of an endogenous opioid peptide, beta-endorphin, plays an important role in the induction of docosahexaenoic acid (DHA)-induced antinociception. It is well known that fatty acids affect intracellular and intercellular signaling as well as the membrane fluidity of neurons. In addition to intracellular actions, unbound free fatty acids (FFAs) can also carry out extracellular signaling by stimulating the G-protein-coupled receptor (GPCR). Among these receptors, GPR40 has been reported to be activated by long-chain fatty acids such as DHA, eicosapentaenoic acid (EPA) and arachidonic acid. In a peripheral area, GPR40 is preferentially expressed in pancreatic beta-cells and is known to be related to the secretion of hormone and peptides. On the other hand, even though this receptor is widely distributed in the central nervous system, reports studying the role and functions of GPR40 in the brain are not found. In this review, we summarize the findings of our recent study about the long-chain fatty acid receptor GPR40 as a novel pain regulatory system.
近年来,脂肪酸在疼痛的发生和抑制过程中的重要功能作用愈发明显。最近,我们还证实内源性阿片肽β-内啡肽的释放,在二十二碳六烯酸(DHA)诱导的抗伤害感受中发挥重要作用。众所周知,脂肪酸会影响细胞内和细胞间信号传导以及神经元的膜流动性。除细胞内作用外,未结合的游离脂肪酸(FFA)还可通过刺激G蛋白偶联受体(GPCR)进行细胞外信号传导。在这些受体中,据报道GPR40可被DHA、二十碳五烯酸(EPA)和花生四烯酸等长链脂肪酸激活。在周边区域,GPR40在胰腺β细胞中优先表达,并且已知与激素和肽的分泌有关。另一方面,尽管该受体广泛分布于中枢神经系统,但尚未发现有关GPR40在大脑中的作用和功能的研究报道。在本综述中,我们总结了我们最近关于长链脂肪酸受体GPR40作为一种新型疼痛调节系统的研究结果。