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Cyclic AMP potentiates amylase secretion by augmentaing the Ca^<2+> -effect in the rat parotid acinar cells.

环AMP通过增强大鼠腮腺腺泡细胞中的Ca 2+ 效应来增强淀粉酶分泌。

基本信息

批准号：
06671844
负责人：
YOSHIMURA Keiichi
金额：
$ 1.41万
依托单位：
Hokkaido Univ.
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

Potentiation of amylase secretion between isoproterenol (Isop) and substance P or carbachol was examined in perifused rat parotid acinar cells. Combined additions of Isop and substance P evoked biphasic changes in amylase secretion with an initial rapid and large peak and the following sustained plateau phase : The magnitudes of the both responses were potentiated. The time course of amylase secretion obtained by a combination of Isop and substance P was similar to that induced by substance P,but not by Isop. Dose-response of amylase secretion by substance P shows that Isop enhanced both the magnitude of the maximum response and the apparent affinity for substance P to evoke the initial peak response ; the EC_<50> in the presence and absence of Isop was about 0.6 nM and 10 nM,respectively. On the other hand, 1 nM substance P was sufficient for evoking the maximum potentiation of the sustained plateau response. Substance P,however, did not change the apparent affinity for the Isop-effec … More t. Similar results were observed when carbachol was used instead of substance P.The effect of Isop was able to be duplicated by dibutyryl cyclic AMP or the agents which increase parotid cyclic AMP.Omission of Ca^<2+> or addition of 5 mM NiCl_2 almost completely abolished the potentiation of the sustained plateau response, but did not affect that of the initial peak. Isop did not enhance the effect of substance P on [Ca^<2+>]_i. Switching to solutions containing higher concentrations of Ca^<2+> during the continuous stimulation with Isop or IBMX,evoked rapid and large peak in amylase secretion ; the magnitude of the response was increased when the permeability of plasma membrane to calcium was increased with ionomycin. The Ca^<2+>-effect was slightly augmented by PDBu, but the effect of PDBu was not augmented by Isop. These results suggest that the potentiation is mainly, if not completely, caused by an interaction between the cyclic AMP and calcium messenger systems at a step distal to the second messenger generation, probably by the cyclic AMP-induced modification of the intracellular events evoked by calcium signal. Less

在灌注的大鼠腮腺腺泡细胞中检查了异丙肾上腺素 (Isop) 和 P 物质或卡巴胆碱之间淀粉酶分泌的增强作用。 Isop 和 P 物质的联合添加引起了淀粉酶分泌的双相变化，具有最初的快速且大的峰值和随后的持续平台期：两种反应的幅度均得到增强。 Isop与P物质联合获得的淀粉酶分泌时程与P物质诱导的淀粉酶分泌时程相似，但与Isop诱导的淀粉酶分泌时程不同。 P 物质分泌淀粉酶的剂量反应表明，Isop 增强了最大响应的幅度和对 P 物质的表观亲和力，以引起初始峰值响应；在存在和不存在Isop的情况下EC 50 分别为约0.6nM和10nM。另一方面，1 nM P 物质足以引起持续平台响应的最大增强。然而，P 物质并没有改变对 Isop 效应的表观亲和力……更多 t。当使用卡巴胆碱代替 P 物质时，观察到类似的结果。二丁酰环 AMP 或增加腮腺环 AMP 的药物能够复制 Isop 的作用。省略 Ca^2+ 或添加 5 mM NiCl_2 几乎完全消除了持续平台响应的增强，但不影响初始峰的增强。 Isop并没有增强P物质对[Ca^2+]_i的作用。在Isop或IBMX连续刺激过程中切换到含有较高浓度Ca^2+的溶液，引起淀粉酶分泌快速且大的峰值；当离子霉素增加质膜对钙的渗透性时，反应的强度增加。 PDBu稍微增强了Ca 2+ -效应，但Isop没有增强PDBu的效应。这些结果表明，增强作用主要（如果不是完全的话）是由第二信使一代远端的环AMP和钙信使系统之间的相互作用引起的，可能是由环AMP诱导的钙信号引起的细胞内事件的修饰引起的。较少的