NOVEL NEURONAL NACHR-TARGETED PEPTIDES

新型神经元 NACHR 靶向肽

• 批准号: 6185998
• 负责人: J MICHAEL MCINTOSH
• 金额: $ 10.71万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6185998
• 关键词: Hermissenda; Xenopus oocyte; neurotoxins; nicotinic receptors; peptide chemical synthesis; receptor binding; toxicant screening

DESCRIPTION (Adapted from applicant's abstract): Nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channels found at the neuromuscular junction and throughout the CNS. Stimulation of central nicotinic receptors appears to enhance concentration and attention in normal individuals and nAChRs have been implicated in several neuropsychiatric disorders including Tourette's syndrome, Alzheimer's disease, schizophrenia, tardive dyskinesia, and Parkinson's disease. Molecular biology has shown that there are numerous subtypes of neuronal nAChRs. Unfortunately, the functional role of each of the diverse CNS receptor subtypes has not been delineated. Venom from the numerous carnivorous marine snail known as Conus contain thousands of neuroactive peptides, many of which appear to target to nAChRs. The major goal of this grant is the application of the powerful neurobiology of Conus toward the development of a bank of subtype-specific nAChR-targeted peptides. In preliminary studies, one such peptide, alpha-conotoxin ImI has been isolated, synthesized, and shown to be specific for a 7-containing neuronal nAChRs. Additional studies show that cone venoms contain other peptides which target to additional neuronal subtypes of nAChRs. The PI will use cloned nAChRs expressed in oocytes and additional methods to detect and isolate novel nAChR-targeted peptides. Purified peptides will be biochemically characterized and synthesized. The oocyte expression system as well as radiolabeling and receptor binding techniques will be used to determine the subtype specificity of the novel ligands. Such ligands would greatly help researchers determine the functional role and significance of neuronal nAChRs in neuropsychiatric health and disease.

性状（改编自申请人摘要）：烟碱乙酰胆碱 受体（nAChR）是在细胞膜上发现的配体门控离子通道家族。 神经肌肉接头和整个CNS。 中枢神经刺激 尼古丁受体似乎可以增强正常人的注意力和集中力。 个体和nAChRs与几种神经精神疾病有关， 包括图雷特综合征、阿尔茨海默病、精神分裂症、 迟发性运动障碍和帕金森病 分子生物学表明 神经元乙酰胆碱受体有很多亚型 可惜 不同CNS受体亚型中的每一种的功能作用尚未被阐明。 描绘的。 从众多的肉食性海洋蜗牛称为芋螺毒液含有 成千上万的神经活性肽，其中许多似乎靶向nAChR。 该基金的主要目标是将强大的神经生物学 芋螺对发展一个银行的亚型特异性nAChR靶向 缩氨酸 在初步研究中，一种这样的肽，α-芋螺毒素ImI具有 已被分离，合成，并显示出特异性的7-含有 神经元nAChRs。 进一步的研究表明，锥毒液含有其他 靶向nAChR的另外的神经元亚型的肽。 的PI 将使用在卵母细胞中表达的克隆nAChRs和其他方法来检测 并分离新的nAChR靶向肽。 纯化的肽将被 生物化学表征和合成。 卵母细胞表达系统 以及放射性标记和受体结合技术将用于 确定新配体的亚型特异性。 这样的配体将 极大地帮助研究人员确定功能的作用和意义， 神经精神健康和疾病中的神经元nAChRs。

项目成果

Activation of nicotinic acetylcholine receptors increases the frequency of spontaneous GABAergic IPSCs in rat basolateral amygdala neurons.

烟碱乙酰胆碱受体的激活增加了大鼠基底外侧杏仁核神经元中自发 GABA 能 IPSC 的频率。

• DOI: 10.1152/jn.00974.2004
• 发表时间: 2005
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Zhu,PingJun;Stewart,RandallR;McIntosh,JMichael;Weight,ForrestF
• 通讯作者: Weight,ForrestF

Nicotinic acetylcholine receptor channels in cat chemoreceptor cells.

猫化学感受器细胞中的烟碱乙酰胆碱受体通道。

• DOI: 10.1007/978-1-4419-9280-2_37
• 发表时间: 2003
• 期刊: Advances in experimental medicine and biology
• 作者: Higashi,Tomoko;Yamaguchi,Shigeki;McIntosh,JMichael;Shirahata,Machiko
• 通讯作者: Shirahata,Machiko

Chronic nicotine selectively enhances alpha4beta2* nicotinic acetylcholine receptors in the nigrostriatal dopamine pathway.

• DOI: 10.1523/jneurosci.2939-09.2009
• 发表时间: 2009-10-07
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Xiao C;Nashmi R;McKinney S;Cai H;McIntosh JM;Lester HA
• 通讯作者: Lester HA