GASTRIC ACID SECRETION, REGULATION OF K+ TRANSPORTERS

胃酸分泌、钾离子转运蛋白的调节

• 批准号: 3232625
• 负责人: EDWIN C RABON
• 金额: $ 13.04万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232625
• 关键词: adenosinetriphosphatase; gastric acid; gastric juice; laboratory rabbit; liposomes; phospholipids; potassium chloride; second messengers; secretion

The long term goal of this study is to define the K+ transport mechanisms used to regulate the transcellular flow of K+ during gastric acid secretion. We have developed an assay of 86Rb- flux which discriminates ATPase and conductance mediated K+ transport to characterize secretory stimulusdependent K+ movement across the basolateral (BLM) and secretory (SM) membranes of vesicle preparations and intact and permeabilized isolated parietal cells of the New Zealand white rabbit. The K+ conductance will be characterized will respect to (i) specific stimulus dependence (ii) cationic selectivity (iii) inhibitor specificity (iii) regulation by specific second messenger mediators. The stimulus response of the Na, K-ATPase will be determined in the isolated cell preparation by the (3H) ouabain binding assay of Hootman and Williams and compared with that of the BLM K+ conductance (J. Physiol (1985) 360:121-134). The K+ conductance of the SM will be solubilized and functionally reconstituted to extend the characterization of this peptide with respect to (i) disenness of inhibitors and physiological moderators and (ii) to begin the initial purfication of the conductance peptide. The appearance of the K+ conductance and specific peptides labeled with the use dependent H,K-ATPase inhibitor (14C) omeprazole will be correlated in stimulated and resting SM preparations to distinguish between possible mechanisms of activation (i.e. appearance of the potassium conductance in parallel with the H,K-ATPase) by a membrane fusion process involving the insertion of a K+ conductance into the SM or covalent modification of an inactive conductance peptide always present in the membrane. These studies suggest that K+ conductances are targets for the physiological regulation of gastric acid secretion. The model system and assays developed here could provide important tools for the study of the pharmacology of the K+ conductance peptide as a means of control of gastric acid secretion.

本研究的长期目标是确定K+输运