PHARMACOLOGY OF NEUROTRANSMITTERS IN HAIR CELL ORGAN

内耳的初级感觉细胞（毛细胞）释放一种 神经递质来刺激听觉神经纤维。的识别 这种递质可能不是已知的神经递质之一， 这个项目的目标。我们已经从毛细胞组织和 视网膜，一种可以刺激支配毛发的传入神经纤维的物质 细胞这种物质似乎是一种强效的、不稳定的、未知的兴奋性物质， 药理活性类似于谷氨酸的氨基酸;然而， 显然不是谷氨酸盐或其他通常研究的物质。 气相色谱/质谱联用技术在纯化 兴奋性物质揭示了一种候选化合物， 与这种未知的兴奋性物质直接相关该化合物 与主要兴奋物质通过三个非常 不同的色谱纯化步骤（凝胶渗透 色谱法、阴离子交换HPLC和阳离子交换HPLC）。 本项目期间的目标是确定化学品 结构的兴奋物质，分析其分布在头发 细胞器官和神经系统，并确定其在头发中的作用 细胞器官功能 除了确定这些问题的内在智力重要性之外， 神经递质释放的毛细胞，这项工作可能有重大意义 耳鼻喉科的实际意义，并应广泛 对听觉系统以外的神经生物学领域的重要性。一旦 生物化学和生理系统， 这种物质是理解，一些研究工具，包括 分子生物学的方法，可以用来理解 过程中的缺陷是否涉及病理过程， 听觉功能可以设计出结构稍有不同的药物 这可能会选择性地阻断这个突触的信息传递。如果 有可能开发出对前庭纤维具有某种特异性的药物， 可能导致运动病和顽固性眩晕的治疗。 明智地使用一种对听觉系统有特异性的药物， 缓解某些形式的周围性耳鸣。兴奋性氨基酸， 从毛细胞组织和视网膜中分离出来， 是神经系统其他部分的神经递质;我们已经知道 它集中在内耳和视网膜中。如果它是本地化的 在神经系统中，它几乎肯定会提供一个 有选择地研究其他地区的传播和作用的方法 的神经系统。

The primary sensory cell of the inner ear (the hair cell) releases a neurotransmitter to excite auditory nerve fibers. The identification of this transmitter, which may not be one of the known neurotransmitters, is the goal of this project. We have purified, from hair cell tissue and from retina, a substance that can excite afferent nerve fibers innervating hair cells. This substance appears to be a potent, unstable, unknown excitatory amino acid with pharmacological activity similar to glutamate; however, it is clearly not glutamate or any other commonly studied substance. Application of gas chromatography/mass spectroscopy to the purified excitatory substance has revealed a candidate compound that may be directly related to this unknown excitatory substance. This compound copurifies with the major excitatory substance through three very different chromatographic purification steps (gel-permeation chromatography, anion-exchange HPLC, and cation-exchange HPLC). The goals during this project period are to identify the chemical structure of the excitatory substance, to analyze its distribution in hair cell organs and in the nervous system, and to determine its role in hair cell organ function. In addition to the intrinsic intellectual importance of identifying the neurotransmitter released by hair cells, this work may have significant practical implications for otolaryngology and should have widespread importance for areas of neurobiology beyond the auditory system. Once the biochemical and physiological systems necessary for making and releasing such a substance are understood, a number of research tools, including molecular biological approaches, can be brought to bear on understanding whether defects in the processes are involved in pathological processes in auditory function. Drugs differing slightly in structure can be devised which might selectively block transmission at this synapse. If it is possible to develop drugs with some specificity for vestibular fibers, a treatment for motion sickness and intractable vertigo would likely result. Judicious use of a drug with specificity for the auditory system might alleviate some forms of peripheral tinnitus. The excitatory amino acid we have isolated from hair cell tissue and from retina is a good candidate to be a neurotransmitter in other pans of the nervous system; we already know it is concentrated in inner ear and in retina. If it is localized discretely within the nervous system, it will almost assuredly provide a means of selectively studying transmission and function of other regions of the nervous system.