Physicochemical Investigation of Taste

味道的理化研究

基本信息

批准号：
7572887
负责人：
Vijay Lyall
金额：
$ 37.55万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-09-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7572887
关键词：
Accounting Acidity Acids Actins Affect Anions Apical Bicarbonate Ion Bicarbonate Ions Bicarbonates Brain Brain Stem Calcium Carbon Dioxide Cell Nucleus Cell Shape Cell Volumes Cell membrane Cell physiology Cells Chemicals Chemoreceptors Chloride-Bicarbonate Antiporters Complex Conscious Coupled Cyclic AMP Cyclic AMP-Dependent Protein Kinases Cytochalasin B Cytoskeleton Data Defense Mechanisms Dependence Diffuse Enzymes Event Extracellular Fluid F-Actin Formates Formic Acids Gastric Acid Heart Image In Vitro Ingestion Investigation Ion Channel Knockout Mice Laboratories Lead Link Measurement Mediating Membrane Metabolism Methods Modification Monitor NADPH Oxidase Nerve Oral cavity Organism Pathway interactions Perception Phase Physiological Play Preparation Process Progress Reports Property Proteins Protons Rattus Receptor Cell Recovery Regulation Relative (related person)Research Research Personnel Reverse Transcriptase Polymerase Chain Reaction Role Saliva Sodium Bicarbonate Stimulus Taste Buds Taste Perception Testing Time Tongue Work apical membrane basolateral membrane chorda tympani fluorescence imaging imaging modality in vivo mouse model prevent programs receptor relating to nervous system research study response sensor voltage voltage clamp

项目摘要

Organisms have evolved mechanisms for controlling the acidity of their intracellular and extracellular fluid compartments to within narrow physiological limits. On the systemic level, cells that function as hydrogen ion sensors in the brain, the heart, the gut,and the tongue evoke reflexive responses that serve to mitigate and ultimately eliminate the acidic challenge. Sour taste receptors detect a decrease in intracellular pH, but in the case of strong acids such as gastric acid (HCI) the mechanism by which protons enter taste cells remains unknown. Preliminary data from NADPH oxidase knockout mice indicate that protons cross the apical membranes of taste cells through two hydrogen ion channels. 1) About 60% of the taste neural response to HCI is absent in NADPH oxidase knockout mice relative to controls, suggesting that one taste proton channel is linked to NADPH oxidase activity. 2) The remaining response to HCI in NADPH oxidase knockout mice is enhanced by cyclic AMP. We will investigate the function of both channels in detail by recording from taste nerves in anesthetized wild type and NADPH oxidase knockout mice under voltage clamp conditions, and by making hydrogen ion flux measurements across the apical and basolateral membranes of taste cells using a polarized single taste bud preparation with fluorescence imaging methods. Transdaction for the phasic part of the sour response is calcium-independent while the tonic part depends on calcium. New data indicate that the phasic transduction involves a decrease in taste cell volume induced by a decrease in intracellular pH. The pH-induced volume decrease depends on cytoskeletal actin. Chemical disruption of the cytoskeleton or osmotically pre-shrinking the cells blocks the phasic response, but not the tonic. We shall explore the link between the phasic sour response and cell volume changes in detail. pH recovery mechanisms in taste cells shape the sour taste response. We have evidence that one of these is pendrin, a chloride-bicarbonate exchanger. We will investigate its role and the role of related transporters in sour responses to carbon dioxide. Since pendrin also transports formate, we will investigate its role in formic acid taste responses. The proposal investigates the three key processes in sour taste: 1) acid entry mechanisms, 2) separate phasic and tonic transduction mechanisms, and 3) pH recovery and adaptation mechanisms. The research will reveal how the sour taste defense mechanism functions to prevent the ingestion of acids.

生物体已经进化出控制细胞内和细胞外液酸度的机制将隔室控制在狭窄的生理范围内。在系统水平上，细胞发挥氢离子的作用大脑、心脏、肠道和舌头中的传感器会引起反射反应，从而减轻和最终消除酸性挑战。酸味受体检测到细胞内 pH 值下降，但在强酸如胃酸 (HCI) 的情况下，质子进入味觉细胞的机制仍然存在未知。 NADPH 氧化酶敲除小鼠的初步数据表明质子穿过顶端通过两个氢离子通道的味觉细胞膜。 1) 大约 60% 的味觉神经反应相对于对照组，NADPH 氧化酶敲除小鼠中不存在 HCI，这表明味觉质子通道与 NADPH 氧化酶活性有关。 2) NADPH氧化酶敲除中对HCl的剩余反应环腺苷酸可增强小鼠的功能。我们将通过记录详细研究这两个通道的功能电压钳条件下麻醉的野生型和 NADPH 氧化酶敲除小鼠的味觉神经，并通过味觉细胞顶膜和基底外侧膜进行氢离子通量测量使用带有荧光成像方法的偏振单味蕾制剂。交易为酸味反应的阶段性部分与钙无关，而滋补性部分则依赖于钙。新数据表明阶段性转导涉及味觉细胞体积的减少，这是由味觉细胞的减少引起的细胞内pH值。 pH 诱导的体积减少取决于细胞骨架肌动蛋白。化学破坏细胞骨架或渗透性预收缩细胞会阻止相位反应，但不会阻止强直。我们将详细探索阶段性酸味反应与细胞体积变化之间的联系。 pH值恢复味觉细胞的机制塑造了酸味反应。我们有证据表明其中之一是pendrin，一种氯化物-碳酸氢盐交换器。我们将研究其作用以及相关转运蛋白在酸中的作用对二氧化碳的反应。由于 pendrin 也运输甲酸，我们将研究它在甲酸中的作用味觉反应。该提案研究了酸味的三个关键过程：1）酸进入机制， 2) 独立的阶段性和紧张性转导机制，以及 3) pH 恢复和适应机制。该研究将揭示酸味防御机制如何发挥作用来防止酸的摄入。