Acetylcholine receptors in taste receptor cells

味觉感受器细胞中的乙酰胆碱受体

• 批准号: 6587954
• 负责人: TATSUYA OGURA
• 金额: $ 7.25万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6587954
• 关键词: Urodela; acetylcholine; apical membrane; biological signal transduction; calcium flux; calmodulin; diacylglycerols; fluorescent dye /probe; genetically modified animals; laboratory mouse; laboratory rat; muscarinic receptor; neuropharmacology; protein kinase C; second messengers; sensory receptors; taste

DESCRIPTION (provided by applicant): Neuroactive substances play important roles as neuromodulators as well as neurotransmitters. One of them, acetylcholine (ACh), is known to be present in taste receptor cells and in nerve fibers innervating taste buds, and ACh agonists improve taste sensation in patients with taste disorders. However, mechanisms underlying physiological functions of ACh in taste receptor cells are not understood. In non-gustatory systems, five subtypes of muscarinic ACh receptors have been identified. I have shown that ACh induces increases in intracellular Ca2+ in taste receptor cells via activation of muscarinic receptors, and that positive immunoreactivity for the M1 subtype of muscarinic receptor is present in both apical and basolateral regions of taste receptor cells. Therefore, I hypothesize that muscarinic ACh receptors may play a role in both taste modulation and taste transduction. Similarly, glutamate receptors function as taste receptors for "umami" taste, in addition to their well known role in synaptic transmission and neuromodulation. In this proposal, I intend to further study the physiological function of ACh and its modulatory effect on taste responses, specifically bitter taste transduction. In addition, ACh receptors at apical membrane of taste receptor cells may function as taste receptors. Three specific aims are: (1) characterize muscarinic ACh receptors in taste cells with pharmacological agents and mice deficient for a specific receptor subtype; (2) determine the second messengers that mediate ACh-induced modulation of bitter responses; and (3) determine whether muscarinic receptors function as taste receptors. For these aims, experiments will be performed using Ca2+ imaging and in situ nerve recording techniques with three animal models: mouse, rat, and mudpuppy. Each species has unique advantages for particular experimental approaches, and all species appear to utilize the same signal transduction mechanisms, in response to ACh. Results from the proposed experiments will provide significant new information about muscarinic ACh receptors in taste buds and their role in taste modulation and perception. In addition, the proposed studies will broaden our understanding about bitter detection mechanisms. This project is expandable to investigate the physiological role of other neuroactive substances in taste cells in future experiments.

描述（由申请人提供）：神经活性物质作为神经调节剂以及神经递质起着重要作用。其中之一，乙酰胆碱（ACH），已知存在于味觉受体细胞和神经纤维中的神经味芽中，而ACH激动剂改善了味觉障碍患者的味觉。然而，尚不了解ACH在味觉受体细胞中生理功能的机制。在非气体系统中，已经确定了五个亚型的毒蕈碱ACH受体。我已经表明，ACH通过激活毒蕈碱受体诱导了味觉受体细胞中细胞内Ca2+的增加，并且在味觉受体细胞的顶端和基底外侧区域都存在毒蕈碱受体M1亚型的阳性免疫反应性。因此，我假设毒蕈碱ACH受体可能在口味调节和味觉转导中起作用。同样，除了众所周知的突触传播和神经调节中的作用外，谷氨酸受体充当“鲜味”味道的味道受体。在此提案中，我打算进一步研究ACH的生理功能及其对味觉反应的调节作用，特别是苦味味道转导。另外，味觉受体细胞顶端膜上的ACH受体可以用作味觉受体。三个特定的目的是：（1）表征具有药理学剂和缺乏特定受体亚型的小鼠味细胞中毒蕈碱ACH受体的表征； （2）确定介导ACh诱导的苦反应调节的第二个使者； （3）确定毒蕈碱受体是否充当味觉受体。对于这些目的，将使用CA2+成像以及使用三种动物模型的原位神经记录技术进行实验：小鼠，大鼠和泥浆。每个物种对于特定的实验方法都有独特的优势，并且所有物种似乎都使用相同的信号转导机制来响应ACH。拟议的实验的结果将提供有关味蕾中毒蕈碱ACH受体及其在味觉调节和感知中的作用的重要新信息。此外，拟议的研究将扩大我们对苦检理机制的理解。该项目可以扩展，以研究未来实验中其他神经活性物质在味觉细胞中的生理作用。