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

研究了大鼠腮腺腺泡细胞中异丙肾上腺素（Isop）与P物质或氨基酚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，先是快速而大的峰值，然后是持续的平台期，两种反应的强度都增强了。Isop与P物质联用后淀粉酶分泌的时间过程与P物质诱导的淀粉酶分泌的时间过程相似，而Isop与P物质诱导的淀粉酶分泌时间过程不同。P物质分泌淀粉酶的剂量反应表明，Isop增强了最大反应的幅度和对P物质的表观亲和力，从而引起初始峰反应；存在和不存在Isop时，EC_<50>分别约为0.6 nM和10 nM。另一方面，1 nM的P物质足以引起持续平台反应的最大增强。而P物质对Isop效应的明显亲和力没有改变。用二丁基环AMP或增加腮腺环AMP的药物可以复制Isop效应。忽略Ca^<2+>或添加5 mM NiCl_2几乎完全消除了持续平台反应的增强，但不影响初始峰的增强。Isop没有增强P物质对[Ca^<2+>]_i的影响。在Isop或IBMX持续刺激时，切换到含有较高浓度Ca^<2+>的溶液，引起淀粉酶分泌快速大和峰值；当离子霉素增加质膜对钙的渗透性时，反应的幅度增加。PDBu能轻微增强Ca^<2+>-效应，但Isop不能增强PDBu的效应。这些结果表明，这种增强主要（如果不是完全）是由环AMP和钙信使系统之间的相互作用引起的，这可能是由环AMP诱导的钙信号引起的细胞内事件的修饰引起的。少

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