PHARMACOLOGY OF NEUROTRANSMITTERS IN HAIR-CELL ORGANS

我们的目标是确定内耳中的神经递质， 他们的行动机制，并说明他们在 毛细胞器官生理学为了识别毛细胞 传递器和其他神经活性物质在内耳，我们有 在鱼内耳的提取物中寻找能够刺激 支配毛细胞的传入纤维。 在上一个项目期间，我们纯化了一种低分子量的 一种可能成为毛细胞传递器的物质。是 集中在毛细胞组织中并刺激传入神经纤维。期间 在下一个项目期间，我们打算确定化学结构， 这种物质，并确定其细胞作用机制。 在上一个项目期间，我们还在内耳提取物中发现 肽，暂时鉴定为降钙素基因相关肽（CGRP）， 也会刺激传入神经元在传出纤维中发现了CGRP 在几个物种的内耳中。CGRP是迄今为止唯一的肽 在传出神经纤维中发现， 影响传入神经纤维的放电率。因此，CGRP是 最有希望的候选研究肽能传出 神经传递素在这个项目期间，我们将研究细胞 CGRP和GABA的作用机制和功能作用， 另一种假定的传出神经递质。 了解神经递质及其细胞的功能作用 作用机制将导致对正常的 耳朵的功能和病理状态。这一理解也将 有助于为耳部疾病的药物干预提供基础。 影响合成、储存、释放、突触后作用的药物， 神经递质的吸收或降解已被证明是一些 最有用的工具，既可以增加我们对生理学的理解， 方法和用于治疗性干预神经系统疾病 系统在这个项目中开发的知识将是至关重要的， 开发影响这些神经递质相关过程的药物 在耳朵里

Our goals are to identify neurotransmitters in the inner ear, to establish the mechanisms by which they act, and to characterize their roles in the physiology of hair-cell organs. In order to identify the hair-cell transmitter and other neuroactive substances in the inner ear, we have looked in extracts of fish inner ears for substances that can excite afferent fibers innervating hair cells. During the previous project period we purified a low-molecular-weight substance that is a candidate to be the hair-cell transmitter. It is concentrated in hair-cell tissue and excites afferent nerve fibers. During the next project period, we intend to identify the chemical structure of this substance and to determine its cellular mechanisms of action. During the previous project period we also found in inner-ear extracts a peptide, tentatively identified as calcitonin gene-related peptide (CGRP), that also excites afferent neurons. CGRP has been found in efferent fibers in the inner ears of several species. CGRP is the only peptide thus far that both has been found in efferent nerve fibers and has been demonstrated to affect the discharge rate of afferent nerve fibers. CGRP is thus the most promising candidate for studies of peptidergic efferent neurotransmitters. In this project period, we will examine the cellular mechanisms of action and functional roles of CGRP as well those of GABA, another putative efferent neurotransmitter. Understanding the functional roles of neurotransmitters and their cellular mechanisms of action will lead to increased understanding about both normal function and pathological states of the ear. This understanding will also help provide a basis for pharmacologic intervention in diseases of the ear. Drugs that affect the synthesis, storage, release, postsynaptic actions, uptake, or degradation of neurotransmitters have proven to be some of the most useful tools both for increasing our understanding of physiological processes and for intervening therapeutically in diseases of the nervous system. The knowledge developed in this project will be crucial for development of drugs that affect these neurotransmitter-related processes in the ear.