ROLE OF NA+/K+ PUMP IN PANCREATIC SECRETION

NA /K 泵在胰腺分泌中的作用

• 批准号: 3445960
• 负责人: SETH R HOOTMAN
• 金额: $ 4.74万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-08-01 至 1986-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3445960
• 关键词: acetylcholine; adenosinetriphosphatase; calcium metabolism; cholecystokinin; cyclic nucleoside monophosphate; cystic fibrosis; exocrine glands; ion transport; membrane permeability; orphan disease /drug; ouabain; pancreatitis; secretin; secretion; vasoactive intestinal peptide

Both acinar and duct cells in the mammalian exocrine pancreas participate information of pancreatic juice. Little is known, however, of the specific mechanisms involved in fluid and electrolyte secretion in either cell type, or how these mechanisms are modulated by hormones and neurotransmitters during stimulus-response coupling. Recent studies suggest that active transport of Na+ across both acinar and duct epithelia is essential to fluid production and that Na+ transport is dependent on activity of the plasma membrane enzyme Na+, K+ activated adenosine triphosphatase (Na+/K+ pump). In the proposed research, the role of the Na+/K+ pump in pancreatinc secretion will be explored. To accomplish this goal, suspensions of dispersed epithelial cells will be prepared from guinea pig pancreas and separated by gradient centrifugation into populations enriched in either acinar or duct cells. The numbers of Na+/K+ pumps in each cell type and their activity will be determined by analysis of ouabain-sensitive 86Rb+ uptake, ouabain-sensitive oxygen consumption and 3H-ouabain binding to the cells. The former two techniques allow direct estimation of Na+/K+ pump-mediated transport activity and its relationship to oxidative metabolism in the cells. The last technique not only measures pump activity, but also provides a means by which the number of Na+/K+ pump molecules in the membranes of each cell type can be determined. The effects of pancreatic secretagogues such as cholecystokinin, VIP, secretin, and acetylcholine on Na+/K+ pump activity will be assessed. Further studies will be carried out to establish the intracellular events that couple receptor activation to alterations in activity of the ion transport enzyme. These will include investigation of ion dependencies, intracellular messengers such as cyclic nucleotides and Ca++, and metabolic energy requirements. The studies proposed will provide information on the ways in which hormones and neurotransmitters modulate Na+/K+ pump activity in acinar and duct epithelia of the exocrine pancreas. This information will be used to construct a cellular model of pancreatic fluid and electrolyte secretion. These data also will establish a strong foundation for further studies probing the dysfunctions in fluid secretion that are characteristic of certain diseases of the pancreas such as pancreatitis and cystic fibrosis.

哺乳动物胰腺外分泌部的腺泡细胞和导管细胞都参与 胰液的信息 然而，人们对具体的 在任一细胞类型中涉及液体和电解质分泌的机制， 或者这些机制是如何被激素和神经递质调节的 在刺激-反应耦合过程中。 最近的研究表明， Na+跨腺泡和导管上皮的转运对于 液体生产和Na+运输依赖于活动的 质膜酶Na+、K+激活的腺苷三磷酸酶（Na+/K+ 泵）。 在拟议的研究中，Na+/K+泵在 将探索胰腺分泌。 为了实现这一目标， 将从豚鼠中制备分散的上皮细胞悬液 胰腺并通过梯度离心分离成富集的群体， 在腺泡或导管细胞中。 每个细胞中Na+/K+泵的数量 类型和它们的活性将通过分析哇巴因敏感的 ~（86）Rb ~+摄取、哇巴因敏感性氧耗和~ 3 H-哇巴因结合 到细胞。 前两种方法可直接测定Na ~+/K ~+ 泵介导的转运活性及其与氧化的关系 细胞内的新陈代谢。 最后一项技术不仅测量泵 活性，而且还提供了一种手段，通过这种手段，Na+/K+泵 可以确定每种细胞类型的膜中的分子。 的 胰腺促分泌素如胆囊收缩素、VIP、促胰液素， 和乙酰胆碱对Na+/K+泵活性的影响。 进一步 将进行研究以确定细胞内事件， 将受体激活与离子转运活性的改变偶联 酵素 这些将包括离子依赖性的研究， 细胞内信使，如环核苷酸和Ca++，以及代谢 能源需求。 拟议的研究将提供关于 激素和神经递质调节Na+/K+泵活性的方式 在胰腺外分泌腺泡和导管上皮中。 这些信息 将用于构建胰液的细胞模型， 电解质分泌 这些数据也将为 为了进一步研究液体分泌功能障碍， 某些胰腺疾病的特征，如胰腺炎和 囊性纤维化

项目成果

Sodium-potassium pump in guinea-pig parotid gland: secretagogue stimulation of ouabain binding to dispersed acini.

豚鼠腮腺中的钠钾泵：促分泌剂刺激哇巴因与分散的腺泡结合。

• DOI: 10.1113/jphysiol.1985.sp015607
• 发表时间: 1985
• 期刊: The Journal of physiology
• 作者: Hootman,SR;Williams,JA
• 通讯作者: Williams,JA