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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Gaba Expression In The Mammalian Taste Bud Functions As A Route Of Inhibitory Cell-to-cell Communication
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Gaba Expression In The Mammalian Taste Bud Functions As A Route Of Inhibitory Cell-to-cell Communication

机译：哺乳动物味蕾中的Gaba表达作为抑制性的细胞间通讯途径

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Recent advances have underscored cell-to-cell communication as an important component of the operation of taste buds with individual taste receptor cells (TRCs) communicating with one another by means of a number of neurotransmitters and neu-ropeptides, although functional roles are not yet understood. Here, we characterize the presence, distribution pattern, phenotype, and functional consequences of a previously undescribed inhibitory route within the taste bud mediated by the classic neurotransmit-ter GABA and its receptors. By using immunocytochemistry, subsets of TRCs within rat taste buds were identified as expressing GABA, and its synthetic enzyme glutamate decarboxylase (GAD). GAD expression was verified with Western blotting. Immunoflu-orescent studies revealed complex coexpression patterns of GAD with the TRC protein markers gustducin, neural cell adhesion molecule, protein gene product 9.5, and synaptosomal-associated protein of 25 kDa that collectively outline hardwired signaling pathways of GABAergic TRCs. RT-PCR and immunocytochemistry demonstrated that both GABA_A and GABA_B receptors are expressed in the taste bud. The later was observed in a subset TRCs paracrine to GAD-expressing TRCs. Physiological effects of GABA were examined by patch clamp recordings. GABA and the GABAA agonists muscimol and isoguvacine enhanced isolated chloride currents in a dose-dependent manner. Also, GABA and the GABA_B agonist baclofen both elicited increases of the inwardly rectifying potassium currents that could be blocked by the GABA_B receptor antagonist CGP 35348 and the G protein blocker GDP-βS. Collectively, these data suggest that GABAergic TRCs are able to shape the final chemosensory output of the bud by means of processes of cell-to-cell modulation.
机译：最近的进展强调了细胞间通讯是味蕾运作的重要组成部分，尽管各个味觉受体细胞（TRC）通过许多神经递质和神经肽相互沟通，但其功能尚未发挥作用了解。在这里，我们表征了经典神经递质GABA及其受体介导的味蕾中先前未描述的抑制途径的存在，分布模式，表型和功能后果。通过使用免疫细胞化学，大鼠味蕾中的TRC子集被鉴定为表达GABA及其合成酶谷氨酸脱羧酶（GAD）。 GAD表达用Western印迹证实。免疫荧光研究显示GAD与TRC蛋白标记gustducin，神经细胞粘附分子，蛋白基因产物9.5和25 kDa的突触体相关蛋白的复杂共表达模式，共同概述了GABA能TRC的硬接线信号通路。 RT-PCR和免疫细胞化学证明GABA_A和GABA_B受体均在味蕾中表达。后者在表达GAD的TRC旁分泌的TRC子集中观察到。通过膜片钳记录检查了GABA的生理作用。 GABA和GABAA激动剂麝香酚和异胍卡因以剂量依赖性方式增强了分离的氯化物电流。此外，GABA和GABA_B激动剂巴氯芬均引起内向整流钾电流的增加，而钾电流可被GABA_B受体拮抗剂CGP 35348和G蛋白阻滞剂GDP-βS阻滞。总体而言，这些数据表明，GABA能的TRC能够通过细胞间调节过程来塑造芽的最终化学感应输出。

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