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

在灌流的大鼠腮腺腺泡细胞中，研究了异丙肾上腺素（Isop）与P物质或卡巴胆碱之间淀粉酶分泌的增强作用。Isop和P物质的联合添加诱发淀粉酶分泌的双相变化，具有初始快速和大的峰值和以下持续的平台期：两种反应的幅度增强。由Isop和P物质的组合获得的淀粉酶分泌的时间过程类似于由P物质诱导的，但不是由Isop。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，以引起初始峰响应;<50>在存在和不存在Isop的情况下，EC_分别约为0.6 nM和10 nM。另一方面，1 nM P物质足以引起持续平台反应的最大增强。然而，P物质并没有改变Isop效应的表观亲和力。 关于我们 t.当用卡巴胆碱代替P物质时，也观察到类似的结果。Isop的作用能被双丁酰环腺苷酸或增加腮腺环腺苷酸的药物复制。不加Ca^2+或加入5 mM NiCl_2几乎完全消除持续平台反应的增强作用，但不影响初始峰的增强作用。Isop不增强P物质对[Ca^&lt;2+&gt;] i的影响。在用Isop或IBMX连续刺激的过程中，切换到含有更高浓度Ca^&lt;2+&gt;的溶液，引起淀粉酶分泌的快速和大的峰值;当用离子霉素增加质膜对钙的渗透性时，反应的幅度增加。PDBu对Ca^&lt;2+&gt;-的作用略有增强，但Isop对PDBu的作用无增强作用。这些结果表明，增效作用主要是，如果不是完全的话，由环腺苷酸和钙信使系统之间的相互作用，在一个步骤远端的第二信使的产生，可能是由环腺苷酸诱导的修改的细胞内事件引起的钙信号。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