CELLULAR CONTROL OF SALIVARY BUFFER CAPACITY

唾液缓冲容量的细胞控制

• 批准号: 2131493
• 负责人: KENNETH W SNOWDOWNE
• 金额: $ 12.23万
• 依托单位: UNIVERSITY OF THE PACIFIC-SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1997-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2131493
• 关键词: acid base balance; acidosis; acinar cell; bicarbonates; buffers; calcium flux; calcium indicator; cell biology; chloride channels; cyclic AMP; cytoplasm; endoplasmic reticulum; hydrogen; imaging /visualization /scanning; inositol phosphates; intracellular; laboratory rat; membrane transport proteins; parotid gland; saliva; secretion; sodium

The principal function of the bicarbonate concentration (HCOminus) of saliva is to buffer changes in the pH of the oral cavity. HCOminus is secreted by the acinar cells of the salivary glands into the lumen through the chloride channel which is under the control of cyclic nucleotides and cytoplasmic calcium. Thus I conclude that salivary buffer capacity is in part directly regulated by the concentration of secondary messengers in the cytoplasm of acinar cells. In this application, I shall show that there is a tight, inverse relationship between pHi and cytoplasmic calcium. The working hypothesis is that cytoplasmic hydrogen ions (i.e., pHi) inhibit calcium influx during activation. This hypothesis predicts that the efflux HCOminus from the parotid cell is a self-limiting phenomenon (i.e., negative feedback regulation involving 2 cytoplasmic ions--calcium and hydrogen). My preliminary evidence shows that cytoplasmic calcium is influenced by pHi in a directly varying relationship. There is also evidence that the Na+/Ca++ exchange and calcium pump of the surface membrane is sensitive to pHi. If this hypothesis could be proven, then this would establish how acinar cells secreted HCOminus without jeopardizing their own capacity to buffer the decrease in pHi that occasions cellular activation. Also this research would give us clues s to the nature of the mechanism responsible for the influx of calcium during activation which is a point of major controversy. The experiments in this application will: 1) establish the relationship between pHi and cytoplasmic calcium in precise, quantitative terms and 2) characterize the pHi-sensitive transporters of calcium ions. This information is essential to establish a foundation for investigating the presence of negative-feedback regulation that controls acinar cell physiology.

碳酸氢盐浓度（Hcominus）的主要功能 唾液是为了缓冲口腔的pH值。 hcominus是 由唾液腺的腺泡细胞分泌到管腔中 在循环核苷酸和控制下的氯化物通道和 细胞质钙。 因此我得出的结论是，唾液缓冲能力在 部分由次级信使的浓度直接调节 腺泡细胞的细胞质。 在此应用程序中，我将证明 PHI和细胞质之间存在紧密的，反比的关系 钙。 有效的假设是细胞质氢离子（即 PHI）抑制激活过程中钙的流入。 该假设预测 来自腮腺细胞的外排hcominus是一个自限制的 现象（即，涉及2个细胞质的负反馈调节 离子 - 钙和氢）。 我的初步证据表明 细胞质钙受PHI的影响直接变化 关系。 也有证据表明NA+/CA ++交换和 表面膜的钙泵对PHI敏感。 如果这个 可以证明假设，这将确定腺泡细胞如何 分泌的hcominus不损害自己的能力缓冲 降低PHI会导致细胞活化。 也是这项研究 将为我们提供有关负责机制的本质的线索 激活过程中钙的流入是重大争议的一点。 本应用程序中的实验将：1）建立关系 在Phi和细胞质钙之间，以精确的定量术语和2） 表征钙离子的PHI敏感转运蛋白。 这 信息对于建立研究基础至关重要 控制腺泡细胞的负反馈调节 生理。