Pereira Renato Tavares dos Santos, Porto Catarina Segreti, Godinho Rosely Oliveira, Abdalla Fernando Maurício Francis
Laboratory of Pharmacology, Instituto Butantan, Av. Vital Brazil 1500, São Paulo, SP 05503-900, Brazil.
Biochem Pharmacol. 2008 May 1;75(9):1827-34. doi: 10.1016/j.bcp.2008.01.016. Epub 2008 Feb 7.
The aim of the present study was to investigate the effects of estrogen lack and estrogen replacement on the production of total [3H]inositol phosphate ([3H]IP) induced by the activation of muscarinic acetylcholine receptors (mAChRs) and on the mechanisms for inactivation of acetylcholine. Hippocampi were obtained from rats in proestrus (PE), ovariectomized for 15 days (C15), ovariectomized for 15 days and then treated with 17beta-estradiol for 7 days (E7) and ovariectomized and immediately treated with 17beta-estradiol for 21 days (E21). Ovariectomy did not change the basal level of total [3H]IP in the hippocampus. 17beta-Estradiol replacement (E7 and E21) reduced the basal level of total [3H]IP. In all experimental groups, carbachol (CCh) caused a concentration-dependent rise in total [3H]IP. The maximum effect was reached with 10(-4) M CCh. The response to 10(-4) M CCh in the hippocampi from C15 and E7 rats was twofold higher than in hippocampi from PE and E21 animals and was blocked by pirenzepine, but not by methoctramine. Ovariectomy or 17beta-estradiol treatment for 7 days did not change neither the total acetylcholinesterase (AChE) activity nor the relative amount of mono- and dimeric G1/G2 and tetrameric G4 globular forms. Conversely, hormonal treatment for 21 days induced an increase in AChE activity of G1/G2 and G4 forms, indicating that 17beta-estradiol stimulates both synthesis and assembly of AChE molecular forms. The present results suggest that the duration and/or a critical period with regard to the initiation of estrogen therapy are important to regulate the function of mAChRs and AChE activity in female rat hippocampus.
本研究的目的是探讨雌激素缺乏和雌激素替代对毒蕈碱型乙酰胆碱受体（mAChRs）激活诱导的总[3H]肌醇磷酸（[3H]IP）产生的影响以及对乙酰胆碱失活机制的影响。从处于动情前期（PE）的大鼠、卵巢切除15天（C15）的大鼠、卵巢切除15天然后用17β-雌二醇治疗7天（E7）的大鼠以及卵巢切除并立即用17β-雌二醇治疗21天（E21）的大鼠获取海马。卵巢切除未改变海马中总[3H]IP的基础水平。17β-雌二醇替代（E7和E21）降低了总[3H]IP的基础水平。在所有实验组中，卡巴胆碱（CCh）引起总[3H]IP浓度依赖性升高。10(-4) M CCh达到最大效应。C15和E7大鼠海马对10(-4) M CCh的反应比PE和E21动物海马中的反应高两倍，且被哌仑西平阻断，但未被甲溴东莨菪碱阻断。卵巢切除或17β-雌二醇治疗7天既未改变总乙酰胆碱酯酶（AChE）活性，也未改变单体和二聚体G1/G2以及四聚体G4球状形式的相对量。相反，激素治疗21天诱导G1/G2和G4形式的AChE活性增加，表明17β-雌二醇刺激AChE分子形式的合成和组装。目前的结果表明，雌激素治疗开始的持续时间和/或关键时期对于调节雌性大鼠海马中mAChRs的功能和AChE活性很重要。
