RECEPTOR REGULATED CALCIUM ENTRY IN EXOCRINE SECRETION

本研究的总体目标是进一步了解 参与启动和控制的细胞机制 外分泌 外分泌活动的刺激 被各种激素和神经递质所影响， 细胞内钙离子（Ca 2+）浓度增加， 一般部分由于初始调动而产生的增加额 细胞内Ca 2+池，部分来自增强的进入， Ca 2+穿过质膜。 已经确定 这种反应也与增加的营业额有关， 膜磷酸肌醇，但之间的关系， 这些膜磷脂的代谢和 膜钙渗透性未知。 现款车型 强调肌醇（聚）的可能意义 磷酸肌醇分解产生的磷酸盐， 受体激活的质膜钙增加 磁导率 特别是，一个重要的“许可”作用， 已提出用于肌醇（1，4，5）三磷酸（I（1，4，5）P3）， 可能与肌醇（1，3，4，5）四磷酸有关 (I(1、3、4、5）P4）。 I（1，4，5）P32+的这种允许作用被认为是 与其已知的动员细胞内Ca 2+的能力有关 店 然而，对毒蕈碱受体的初步研究- 激活细胞内Ca 2+浓度的增加， 鸟类的鼻腺没有检测到 细胞内的Ca 2+。 这表明，目前 模型可能需要修改，也许可以考虑其他 I（1，4，5）P3的可能作用，以解释其明显的 允许的作用，或通过考虑I（1，3，4，5）P的可能性 能够直接增加激活Ca 2+流入， 组织. 这个问题将通过调查关系来研究 肌醇磷酸的产生和 在分离的细胞中使用阴离子- 交换色谱和荧光技术。 在 此外，外源性肌醇磷酸对 将通过以下技术在单个分离细胞中检查Ca 2+内流 结合全细胞透析，使用贴片移液管，和 钙离子依赖indo-1同时显微荧光分析法 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.