Human glycine α1 receptor inhibition by quercetin is abolished or inversed by α267 mutations in transmembrane domain 2

• Published in: Brain research 2007, Vol.1161, p.1-10
• Main Authors: Lee, Byung-Hwan, Lee, Jun-Ho, Yoon, In-Soo, Lee, Joon-Hee, Choi, Sun-Hye, Pyo, Mi Kyung, Jeong, Sang Min, Choi, Woo-Sung, Shin, Tae-Joon, Lee, Sang-Mok, Rhim, Hyewhon, Park, Yong-Sun, Han, Ye Sun, Paik, Hyun-Dong, Cho, Ssang-Goo, Kim, Cheon-Ho, Lim, Yoong-Ho, Nah, Seung-Yeol
• Format: Article
• Language: English
• Subjects: Aminoacid receptors (glycine, glutamate, gaba); Biological and medical sciences; Cell receptors; Cell structures and functions; Flavonoid; Fundamental and applied biological sciences. Psychology; Glycine; Glycine receptor; Ligand-gated ion channel; Molecular and cellular biology; Neurology; Quercetin; Xenopus oocytes
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2007.05.057

Abstract Quercetin, one of the flavonoids, is a compound of low molecular weight found in fruits and vegetables. Besides its antioxidative effect, quercetin also shows a wide range of diverse neuropharmacological actions. However, the cellular mechanisms of quercetin's actions, especially on ligand-gated ion channels and synaptic transmissions, are not well studied. We investigated the effect of quercetin on the human glycine α1 receptor channel expressed in Xenopus oocytes using a two-electrode voltage clamp technique. Application of quercetin reversibly inhibited glycine-induced current ( IGly ). Quercetin's inhibition depends on its dose, with an IC50 of 21.5 ± .2 μM. The inhibition was sensitive to membrane voltages. Site-directed mutations of S267 to S267Y but not S267A, S267F, S267G, S267K, S267L and S267T at transmembrane domain 2 (TM2) nearly abolished quercetin-induced inhibition of IGly . In contrast, in site-directed mutant receptors such as S267 to S267I, S267R and S267V, quercetin enhanced IGly compared to the wild-type receptor. The EC50 was 22.6 ± 1.4, 25.5 ± 4.2, and 14.5 ± 3.1 μM for S267I, S267R and S267V, respectively. These results indicate that quercetin might regulate the human glycine α1 receptor via interaction with amino acid residue α267 and that α267 plays a key role in determining the regulatory consequences of the human glycine α1 receptor by quercetin.