5-HT_2和5-HT_3受体在外周初级感觉神经末梢痛反应和痛调制中的相互作用  

INTERACTION OF 5-HT_2 AND 5-HT_3 RECEPTOR SUBTYPE IN 5-HT-INDUCED NOCICEPTIVE RESPONSES IN PERIPHERAL PRIMARY SENSORY NERVE ENDING

作　　者：张健[1] 胡旺平[2] 周克纯[2] 罗加烈[2] 樊友珍[2] 茹立强[2] 李之望[2] 

机构地区：[1]深圳市南山医院神经内科,广东深圳518052 [2]华中科技大学同济医学院神经生物学系

出　　处：《中国应用生理学杂志》2006年第1期40-44,共5页Chinese Journal of Applied Physiology

摘　　要：目的:探讨5-HT2和5-HT3受体亚型在5-HT引起外周痛反应和痛调制中的相互作用及其机制;方法:在大鼠三叉神经节神经元标本上应用全细胞膜片钳技术记录5-羟色胺激活电流(I5-HT),并结合痛行为实验进行观察。结果:在大多数受检细胞(54/88,61.4%)特别是中、小型细胞外加5-HT可引起一快去敏感的内向电流,此内向电流能被5-HT3受体特异性激动剂2-甲基-5-羟色胺所模拟,被5-HT3受体拮抗剂ICS250-930可逆性阻断,而5-HT2受体激动剂α-甲基-5-羟色胺则有明显增强I5-HT的作用,5-HT1受体激动剂R-(+)-UH301无明显反应。在进一步的整体清醒动物的行为学试验中我们观察到,大鼠后肢掌底皮下注射5-HT(10-5,10-4和10-3mol/L)引起浓度依赖性的痛行为反应,而用5-HT2和5-HT3受体特异性拮抗剂Cyproheptadine和ICS250-930分别阻断相应受体亚型后,5-HT引起的痛行为反应的强度序列为:5-HT>5-HT+ICS>5-HT+Cyp。结论:本文结果提示:5-HT所引起的痛反应中,在初级感觉神经元水平5-HT3受体可能仅起着启始作用,而5-HT2受体则在伤害性信息的维持和调制过程中发挥更大的作用。Aim： To study the correlation between 5-HT-induced pain response and the contribution by individual 5-HTR subtypes including 5-HT1R, 5-HT2R and 5-HT3R at the level of peripheral primary afferent. Methods： The experiments were done on acutely isolated trigeminal ganglion（TG） neurons using whole-cell patch clamp technique and the nociceptive effect was observed on behavior experi- ments by intraplantar injection of test drugs. Results： The majority of cells examined responded to 5-HT in a manner of concentration dependence（ 10^-6～10^-3mol/）（61.4% , 54/88） and with a fast activating and rapid desensitizing inward current （Is_rrr）, which was thought to be mediated by the activation of 5-HT3R, since it could be blocked by 5-HT3R antagonist ICS 205930 and mimicked by 5-HT3R agonist 2-methyl-5-HT. It was found that I5-HT was potentiated by 5-HT2R agonist α-methyl-5-HT markedly, while 5-HTIR agonist R-（ ＋ ）-UH 301 did not. In behavioral experiment performed on conscious rats, intraplantar injection of 5-HT（ 10^-5,10^-4 and 10^-3mol/L） induced an increment of cumulative lifting time first 20 min in a manner of concentration dependence. By dissociating 5-HTR subtypes using their corresponding antagonists （ ICS and CYP） the potency order of hindpaw lifting time was identified as follows： 5-HT〉 5-HT ＋ ICS〉 5-HT ＋ CYP. Conclusion： The results suggest that in 5-HT-induced nociceptive response at the primary sensory level 5-HT3R may play a role of initiation,but 5-HT2R mediates maintaining and modulatory effect in the processes of nociceptive information convey.

关 键 词：5-HTl受体 5-HT2受体 5-HT3受体 膜片钳技术 大鼠 5-HT-引起的疼痛 三叉神经节神经元 痛行为实验 

分 类 号：Q429[生物学—神经生物学]