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人胰淀素受体和烟碱乙酰胆碱受体在大鼠大脑神经元上的功能偶联作用

李宗明, 李秀凤

Neurobiology Laboratory, Luohe Medical College, Luohe 462002, China； The First Affiliated Hospital of Luohe Medical College, Luohe Central Hospital, Luohe 462000, China

摘要

人胰淀素(hAmylin)是由分泌胰岛素的胰岛B细胞释放，作用于靶组织，维持细胞的兴奋性和葡萄糖在体内的稳态。hAmylin分泌异常会引起人类的疾病，特别是阿尔茨海默氏病(Alzheimer’s disease, AD)。目前对于hAmylin通过激活什么样的受体从而产生脑神经元的神经毒性仍然不清楚。已知烟碱乙酰胆碱受体(nicotinic acetylcholine receptors, nAChRs)是引发多种神经性疾病的关键因素。本研究通过记录hAmylin和烟碱对基底前脑神经元的全细胞电流和膜电位的影响，来确定hAmylin受体和烟碱受体两者之间的相互作用。在酶解分离的基底前脑Broca区(diagonal band of Broca, DBB)胆碱能神经元上进行全细胞膜片钳记录，结果显示，hAmylin或烟碱单独应用，均引起剂量(1 nmol/L~20 µmol/L)依赖性膜电位的去极化和DBB神经元放电频率增加。hAmylin受体拮抗剂AC253，不仅阻断hAmylin的兴奋作用，而且也阻断烟碱对神经元的兴奋作用；同样，使用nAChR竞争性拮抗剂二氢-β-刺桐啶碱(dihydro-β-erythroidine, DHβE)，可以阻断烟碱和hAmylin对DBB神经元的兴奋作用。以上结果提示，hAmylin受体和nAChRs受体在DBB神经元可能是功能偶联的，协同影响DBB神经元的兴奋性。

关键词： 人胰淀素受体; 烟碱乙酰胆碱受体; 膜片钳; 阿尔茨海默氏病

分类号：R338

Functional coupling reactions of human amylin receptor and nicotinic acetylcholine receptors in rat brain neurons

LI Zong-Ming, LI Xiu-Feng

漯河医学高等专科学校神经生物学实验室，漯河 462000；漯河医学高等专科学校第一附属医院，漯河市中心医院，漯河 462000

Abstract

Human amylin (hAmylin) is co-released with insulin from pancreatic B-cells and the actions of this peptide on its target tissues maintain the cell excitability and glucose homeostasis. Inappropriate control of hAmylin secretion may result in human disease, particularly Alzheimer’s disease (AD). It’s unknown that which kind of receptor is activated by human amylin, leading to the neurotoxicity in neurons of brain. Nicotinic acetylcholine receptors (nAChRs) are known to play a critical role in a variety of nervous diseases. In the present study, we sought to determine the inter-relationships between these two receptors by examining the actions of hAmylin and nicotine on whole-cell currents and membrane potential in basal forebrain neurons. Whole cell patch-clamp recordings were performed on enzymatically dissociated neurons of the diagonal band of Broca (DBB), a cholinergic basal forebrain nucleus. The results showed that either hAmylin or nicotine individually caused a dose-dependent (1 nmol/L–20 µmol/L) membrane depolarization and an increase in firing frequency of DBB neurons. Application of AC253, an amylin receptor antagonist, blocked the excitatory effects of not only hAmylin but also nicotine; dihydro-β-erythroidine (DHβE), a nAChR antagonist, also blocked the effects of nicotine and hAmylin. These electrophysiological results suggest that hAmylin receptor and nAChRs on DBB neurons are coupled and may function in a co-operative manner to influence the excitability of DBB neurons. This finding is important for us to understand the cause and mechanisms of AD.

Key words: human amylin receptor; nicotinic acetylcholine receptors; patch clamp; Alzheimer’s disease

收稿日期：2011-05-30　　录用日期：2011-08-29

通讯作者：李宗明　　E-mail: lizongming3@126.com

引用本文：

李宗明, 李秀凤. 人胰淀素受体和烟碱乙酰胆碱受体在大鼠大脑神经元上的功能偶联作用[J]. 生理学报 2012; 64 (1): 69-74.

LI Zong-Ming, LI Xiu-Feng. Functional coupling reactions of human amylin receptor and nicotinic acetylcholine receptors in rat brain neurons. Acta Physiol Sin 2012; 64 (1): 69-74 (in Chinese with English abstract).