Dracheva Stella, Elhakem Sharif L, Marcus Sue M, Siever Larry J, McGurk Susan R, Haroutunian Vahram
Department of Psychiatry, Mount Sinai School of Medicine and Bronx Veterans Affairs Medical Center, New York 10468, USA.
J Neurochem. 2003 Dec;87(6):1402-12. doi: 10.1046/j.1471-4159.2003.02115.x.
Serotonin 2C receptor (5-HT2CR) heterogeneity in the brain occurs mostly from two different sources: (i) 5-HT2CR mRNA undergoes adenosine-to-inosine editing events at five positions, which leads to amino acid substitutions that produce receptor variants with different pharmacological properties; (ii) 5-HT2CR mRNA is alternatively spliced, resulting in a truncated mRNA isoform (5-HT2CR-tr) which encodes a non-functional serotonin receptor. 5-HT2CR mRNA editing efficiencies and the expression of the full-length and the truncated 5-HT2CR mRNA splice isoforms were analyzed in the prefrontal cortex of elderly subjects with schizophrenia vs. matched controls (ns = 15). No significant differences were found, indicating that there are no alterations in editing or alternative splicing of 5-HT2CRs that are associated with schizophrenia in persons treated with antipsychotic medications. Quantitation of 5-HT2CR and 5-HT2CR-tr mRNA variants revealed that the expression of 5-HT2CR-tr was approximately 50% of that observed for the full-length isoform.
大脑中5-羟色胺2C受体(5-HT2CR)的异质性主要源于两个不同的来源:(i)5-HT2CR信使核糖核酸(mRNA)在五个位置发生腺苷到次黄苷的编辑事件,这导致氨基酸替换,产生具有不同药理学特性的受体变体;(ii)5-HT2CR mRNA发生可变剪接,产生一种截短的mRNA异构体(5-HT2CR-tr),其编码一种无功能的5-羟色胺受体。在患有精神分裂症的老年受试者与匹配的对照组(每组n = 15)的前额叶皮质中分析了5-HT2CR mRNA编辑效率以及全长和截短的5-HT2CR mRNA剪接异构体的表达。未发现显著差异,表明在接受抗精神病药物治疗的人群中,与精神分裂症相关的5-HT2CR的编辑或可变剪接没有改变。对5-HT2CR和5-HT2CR-tr mRNA变体的定量分析显示,5-HT2CR-tr的表达约为全长异构体观察值的50%。