Hydrogen/Potassium Atpase and Gastric Acid Secretion

氢/钾天冬氨酸蛋白酶和胃酸分泌

• 批准号: 6622613
• 负责人: DANIELLE L SMITH
• 金额: $ 4.2万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-16 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6622613
• 关键词: cytoskeleton; gastric acid; gastrointestinal epithelium; gastrointestinal function; gene targeting; genetically modified animals; hydrogen potassium exchanging ATPase; immunoelectron microscopy; immunofluorescence technique; intracellular transport; laboratory mouse; minority health professional; molecular pathology; molecular site; predoctoral investigator; protein localization; protein structure function; protein transport; secretion; site directed mutagenesis; ulcer

DESCRIPTION (provided by applicant) Gastric acid secretion contributes to ulcer formation and its control is one of the primary targets of pharmacologic agents employed to promote ulcer healing. Thus, a more thorough understanding of the cellular and molecular mechanisms which control acid secretion will be extremely valuable in future efforts to explain ulcer pathogenesis and treat ulcer pathology. The cytoplasmic tail of the H,K-ATPase n-subunit possesses a tyrosine-based endocytosis motif which is necessary for the re-internalization of the holoenzyme and therefore contributes to the cessation of gastric acid secretion in transgenic animals. However, the mechanism through which this endocytosis signal is silenced to permit prolonged acid secretion during gastric stimulation has yet to be determined. It is proposed that the cytoskeleton that underlies the apical secretory canalicular membrane prevents the Is-subunit's constitutive endocytosis signal from mediating the holoenzyme's internalization. With the utilization of transgenic mice, the role of identified molecular domains in the H,K-ATPase in regulating gastric acid secretion may be elucidated.

描述（由申请人提供） 胃酸分泌有助于溃疡形成，其控制是其中之一 用于促进溃疡愈合的药物的主要目标。 因此，对细胞和分子机制有更深入的了解 控制酸分泌的药物在未来的努力中将非常有价值 解释溃疡发病机制并治疗溃疡病理。 H,K-ATPase n 亚基的细胞质尾部具有基于酪氨酸的 内吞作用基序是重新内化所必需的 全酶，因此有助于停止胃酸分泌 在转基因动物中。然而，这种内吞作用的机制 信号被静音，以允许胃酸长时间分泌 刺激措施尚未确定。有人提出，细胞骨架 位于顶端分泌小管膜的下方，可防止 Is 亚基的 介导全酶的组成型内吞信号 内化。随着转基因小鼠的利用， 鉴定出 H,K-ATP 酶中调节胃酸的分子结构域 可以阐明分泌。