RECEPTOR REGULATED CALCIUM ENTRY IN EXOCRINE SECRETION

这项研究的总体目的是进一步了解 参与启动和控制的细胞机制 外分泌。对外分泌活动的刺激 通过各种荷尔蒙和神经递质参与 细胞内钙离子(钙离子)浓度的增加， 通常部分是由最初的动员造成的增加 细胞内的钙离子池，部分来自增强的内流 Ca~(2+)通过质膜。已经确定， 这样的反应也与营业额的增加有关 膜磷脂，但两者之间的关系 这些膜磷脂的代谢和血管内皮细胞的变化 膜钙通透性尚不清楚。当前型号 强调肌醇(聚)的可能意义 由肌醇磷脂分解产生的磷酸盐，在诱导 受体激活的质膜钙升高 渗透性。特别是，一个基本的“允许的”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)四氢磷酸 (I(1，3，4，5)P4)。I(1，4，5)P32+的这种允许作用被认为是 与其动员细胞内钙离子的已知能力有关 商店。然而，对M受体的初步研究- 激活后细胞内钙离子浓度升高 禽类鼻腺没有检测到任何移动 该组织中的细胞内钙离子。这表明目前的情况 可能需要修改模型，或许可以考虑其他 I(1，4，5)P3可能的行为解释其表观 允许角色，或考虑I(1，3，4，5)P的可能性 能直接增加脑内钙离子的活化内流 组织。 这个问题将通过调查这些关系来研究。 在肌醇磷酸盐产量和 用阴离子交换技术测定游离细胞内钙离子浓度 交换层析和荧光技术。在……里面 此外，外源性肌醇磷酸盐的直接作用 钙离子进入将通过一种技术在单个分离的细胞中进行检测 结合全细胞透析，使用贴片移液管，以及 同时微量荧光法测定钙依赖的INDO-1 荧光。

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.