Erlander M G, Lovenberg T W, Baron B M, de Lecea L, Danielson P E, Racke M, Slone A L, Siegel B W, Foye P E, Cannon K
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3452-6. doi: 10.1073/pnas.90.8.3452.
We report two serotonin (5-hydroxytryptamine, 5-HT) receptors, MR22 and REC17, that belong to the G-protein-associated receptor superfamily. MR22 and REC17 are 371 and 357 amino acids long, respectively, as deduced from nucleotide sequence and share 68% mutual amino acid identity and 30-35% identity with known catecholamine and 5-HT receptors. Saturable binding of 125I-labeled (+)-lysergic acid diethylamide to transiently expressed MR22 in COS-M6 cells was inhibited by ergotamine > methiothepin > 5-carboxamidotryptamine > 5-HT. For REC17, the rank of potency was ergotamine > 5-carboxamidotryptamine > methiothepin > methysergide > 5-HT. Both were insensitive to 5-HT1A, 5-HT1D or 5-HT2 serotonergic ligands [8-hydroxy-2-(di-n-propylamino)tetralin, sumatriptan, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]. The mRNAs encoding MR22 were detected in the CA1 region of hippocampus, the medial habenula, and raphe nuclei. In contrast, mRNAs encoding REC17 were found throughout the rat central nervous system. We propose that REC17 and MR22, designated as 5-HT5 alpha and 5-HT5 beta, represent a distinct subfamily of 5-HT receptors.
我们报道了两种血清素（5-羟色胺，5-HT）受体，MR22和REC17，它们属于与G蛋白相关的受体超家族。根据核苷酸序列推断，MR22和REC17分别由371和357个氨基酸组成，它们的氨基酸序列一致性为68%，与已知的儿茶酚胺和5-HT受体的一致性为30%-35%。在COS-M6细胞中瞬时表达的MR22上，125I标记的（+）-麦角酰二乙胺的饱和结合被麦角胺>甲硫哒嗪>5-羧酰胺色胺>5-HT抑制。对于REC17，效力顺序为麦角胺>5-羧酰胺色胺>甲硫哒嗪>甲基麦角新碱>5-HT。两者对5-HT1A、5-HT1D或5-HT2血清素能配体[8-羟基-2-（二正丙基氨基）四氢萘、舒马曲坦和1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷]均不敏感。在海马体CA1区、内侧缰核和中缝核中检测到编码MR22的mRNA。相比之下，在大鼠中枢神经系统中均发现了编码REC17的mRNA。我们提出，REC17和MR22，分别命名为5-HT5α和5-HT5β，代表了一个独特的5-HT受体亚家族。
