Mendes de Freitas Rivelilson, Aguiar Lissiana M V, Vasconcelos Silvânia M M, Sousa Francisca C F, Viana Glauce S B, Fonteles Marta M F
Department of Physiology and Pharmacology, Laboratory of Neuropharmacology, School of Medicine, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, Fortaleza 60431-970, CE, Brazil.
Life Sci. 2005 Dec 5;78(3):253-8. doi: 10.1016/j.lfs.2005.04.045. Epub 2005 Aug 30.
The present study was undertaken in order to investigate the muscarinic (M(1)), dopaminergic (D(1) and D(2)) and serotonergic (5-HT(2)) receptors densities in hippocampus and striatum of Wistar rats after status epilepticus (SE) induced by pilocarpine. The control group was treated with 0.9% saline. An other group of rats received pilocarpine (400 mg/kg, s.c.) and both groups were sacrificed 1 h after treatment. The results have shown that pilocarpine administration and resulting SE produced a downregulation of M(1) receptor in hippocampus (41%) and striatum (51%) and an increase in the dissociation constant (K(d)) values in striatum (42%) alone. In both areas the 5-HT(2) receptor density remained unaltered, but a reduction (50%) and an increase (15%) in the K(d) values were detected in striatum and hippocampus, respectively. D(1) and D(2) receptor densities in hippocampus and striatum remained unaltered meanwhile K(d) values for D(1) receptor declined significantly, 33% in hippocampus and 26% in striatum. Similarly, K(d) values for D(2) decreased 55% in hippocampus and 52% in striatum. From the preceding results, it is clear that there is a possible relation between alterations in muscarinic receptor density and others systems studied as well as they suggest that changes in dissociation constant can be responsible for the establishment of pilocarpine-induced SE by altering the affinity of neurotransmitters such as acetylcholine, dopamine and serotonine.
本研究旨在调查匹鲁卡品诱导癫痫持续状态(SE)后,Wistar大鼠海马和纹状体中M(1)毒蕈碱型、D(1)和D(2)多巴胺能型以及5-HT(2)5-羟色胺能型受体的密度。对照组用0.9%生理盐水治疗。另一组大鼠接受匹鲁卡品(400mg/kg,皮下注射),两组在治疗后1小时处死。结果显示,给予匹鲁卡品并导致SE后,海马中M(1)受体下调41%,纹状体中下调51%,且仅纹状体中的解离常数(K(d))值增加42%。在两个区域中,5-HT(2)受体密度均未改变,但纹状体和海马中的K(d)值分别降低了50%和增加了15%。海马和纹状体中D(1)和D(2)受体密度未改变,同时D(1)受体的K(d)值显著下降,海马中下降33%,纹状体中下降26%。同样,D(2)受体的K(d)值在海马中下降55%,在纹状体中下降52%。从上述结果可以清楚地看出,毒蕈碱型受体密度的改变与所研究的其他系统之间可能存在关联,并且它们表明解离常数的变化可能通过改变乙酰胆碱、多巴胺和血清素等神经递质的亲和力而导致匹鲁卡品诱导的SE的发生。