RECEPTOR REGULATED CALCIUM ENTRY IN EXOCRINE SECRETION

受体调节外分泌分泌中的钙进入

• 批准号: 3298002
• 负责人: Trevor J. Shuttleworth
• 金额: $ 12.44万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3298002
• 关键词: calcium transporting ATPase; cell membrane; ducks; exocrine glands; hormone receptor; hormone regulation /control mechanism; membrane lipids; membrane permeability; neurotransmitters; phosphatidylinositols; phospholipids; secretion

The overall aim of this research is further understanding of the cellular mechanisms involved in the initiation and control of exocrine secretion. The stimulation of exocrine secretory activity by various hormones and neurotransmitters is known to involve increases in intracellular calcium ion (Ca2+) concentrations, increases that generally result partly from an initial mobilization of intracellular Ca2+ pools and partly from an enhanced entry of Ca2+ across the plasma membrane. It has been established that such responses are also associated with the increased turnover of membrane phosphoinositides, but the relationship between the metabolism of these membrane phospholipids and changes in membrane calcium permeability are unknown. Current models emphasize the possible significance of the inositol (poly) phosphates, produced by phosphoinositide breakdown, in inducing the receptor-activated increase in plasma membrane calcium permeability. In particular, an essential "permissive" role has been proposed for inositol (1,4,5) trisphosphate (I(1,4,5)P3), possibly in association with inositol (1,3,4,5) tetrakisphosphate (I(1,3,4,5)P4). This permissive role of I(1,4,5)P32+ is believed to be associated with its known ability to mobilize intracellular Ca2+ stores. However, preliminary studies on muscarinic receptor- activated increases in intracellular Ca2+ concentration in the avian nasal gland have failed to detect any mobilization of intracellular Ca2+ in this tissue. This suggests that current models may need to be modified, perhaps by considering other possible actions of I(1,4,5)P3 to account for its apparent permissive role, or by considering the possibility of I(1,3,4,5)P being directly capable of increasing activating Ca2+ influx in this tissue. This problem will be studied by investigating the relationships between inositol phosphate production and increases in intracellular Ca2+ concentration in isolated cells using anion- exchange chromatography and fluorimetric techniques. In addition, the direct effects of exogenous inositol phosphates on Ca2+ entry will be examined in single isolated cells by a technique combining whole-cell dialysis, using a patch-pipette, and simultaneous microfluorimetry of Ca2+ -dependent indo-1 fluorescence.

这项研究的总体目的是进一步了解 涉及引发和控制的细胞机制 外分泌分泌。 刺激外分分泌活动 已知通过各种激素和神经递质涉及 细胞内钙离子（Ca2+）浓度增加， 通常由初始动员而导致的增加 细胞内Ca2+池的组合，部分是从增强的入口 跨质膜的Ca2+。 已经确定了 这种回应也与增加的营业额增加有关 膜磷酸肌醇，但 这些膜磷脂的代谢和变化 膜钙渗透性尚不清楚。 当前模型 强调肌醇（poly）的可能意义 磷酸盐，由磷酸肌醇分解产生，诱导 受体激活的质膜钙的增加 渗透性。 特别是，重要的“允许”角色具有 提出了肌醇（1,4,5）三磷酸（I（1,4,5）P3）， 可能与肌醇（1,3,4,5）四磷酸 （I（1,3,4,5）P4）。 I（1,4,5）p32+的允许作用被认为是 与已知的动员细胞内Ca2+的能力有关 商店。 但是，关于毒蕈碱受体的初步研究 激活的细胞内Ca2+浓度的增加 禽鼻腺未能检测到任何动员 该组织中的细胞内Ca2+。 这表明当前 可能需要修改模型，也许是考虑其他 I（1,4,5）P3的可能采取的措施来解释其明显 允许的角色，或考虑I（1,3,4,5）P的可能性 直接能够增加激活Ca2+涌入 组织。 将通过研究关系来研究这个问题 在肌醇磷酸盐的产生和增加之间 细胞内Ca2+浓度在分离的细胞中使用阴离子 - 交换色谱和氟化技术。 在 此外，外源性肌醇磷酸盐的直接影响对 CA2+进入将通过一种技术在单个孤立的单元中检查 使用贴片板组合全细胞透析，然后 Ca2+依赖性Indo -1的同时微氟甲氟二氟化 荧光。