PHARMACOLOGY OF NEUROTRANSMITTERS IN HAIR-CELL ORGANS

我们的目标是识别内耳中的神经递质，以建立 他们采取行动的机制，并确定他们在 毛细胞器官生理学。为了识别毛细胞 内耳中的递质和其他神经活性物质，我们有 在鱼内耳的提取物中寻找可以兴奋的物质 支配毛细胞的传入纤维。 在之前的项目期间，我们提纯了一种低分子量的 毛细胞传递体的候选物质。它是 集中在毛细胞组织中，刺激传入神经纤维。在.期间 在下一个项目期间，我们打算确定 这种物质，并确定其细胞的作用机制。 在之前的项目期间，我们还在内耳提取物中发现了一种 多肽，初步鉴定为降钙素基因相关肽(CGRP)， 这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。到目前为止，CGRP是唯一的多肽 已经在传出神经纤维中发现了这两种物质，并且已经证明 影响传入神经纤维的放电速度。因此，CGRP是 肽能传出神经最有希望的研究对象 神经递质。在本项目期间，我们将研究蜂窝 CGRP和GABA的作用机制和功能作用， 另一种可能的传出神经递质。 了解神经递质及其细胞的功能作用 作用机制将导致对这两种正常情况的更多了解 耳朵的功能和病理状态。这一谅解还将 有助于为耳部疾病的药物干预提供依据。 影响合成、储存、释放、突触后活动的药物， 神经递质的摄取或退化已被证明是 最有用的工具，既可以增加我们对生理学的理解 神经性疾病的治疗过程和干预 系统。在这个项目中开发的知识将对 影响这些神经递质相关过程的药物的开发 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.