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) 的主要函数 唾液的作用是缓冲口腔pH值的变化。 HCO 减为 由唾液腺的腺泡细胞分泌到腔内 受环核苷酸控制的氯离子通道 细胞质钙。 因此我得出结论，唾液缓冲能力是 部分直接受第二信使浓度调节 腺泡细胞的细胞质。 在这个应用程序中，我将证明 pHi 和细胞质之间存在紧密的反比关系 钙。 工作假设是细胞质氢离子（即 pHi) 抑制活化过程中的钙流入。 这个假设预测 腮腺细胞的 HCOminus 流出是一种自限性 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。 还有证据表明 Na+/Ca++ 交换和 表面膜的钙泵对pHi敏感。 如果这个 假设可以被证明，那么这将确定腺泡细胞如何 分泌 HCOminus 而不损害自身缓冲能力 pHi 降低导致细胞激活。 还有这个研究 将为我们提供线索，了解造成这一现象的机制的性质 活化过程中钙的流入是一个主要争议点。 本应用程序中的实验将：1) 建立关系 pHi 和细胞质钙之间的精确、定量术语以及 2) 表征 pHi 敏感的钙离子转运蛋白。 这 信息对于建立调查基础至关重要 存在控制腺泡细胞的负反馈调节 生理。