Kiehne Karlheinz, Herzig Karl Heinz, Otte Jan M, Fölsch Ulrich R
I. Medizinische Universitätsklinik, Christian-Albrechts Universität Kiel, Schittenhelmstr. 12, 24105, Kiel, Germany.
Regul Pept. 2002 May 15;105(2):131-7. doi: 10.1016/s0167-0115(02)00015-0.
Stimulation of low-affinity CCK-1 receptors on pancreatic acini leads to inhibition of enzyme secretion. We studied signal transduction mechanisms to identify potential causes for the reduced secretion.
Co-stimulation experiments with CCK, CCK-JMV-180, and bombesin revealed an inhibition of bombesin-stimulated enzyme secretion by low-affinity CCK-1 receptors. Binding of 125I-gastrin-releasing peptide (the mammalian analogue of bombesin) to acini after CCK preincubation was not altered. After a short preincubation of acini with high concentrations of CCK, intracellular calcium remained responsive to bombesin. In contrast to bombesin or CCK at concentrations of 10(-10) M or lower, high concentrations of CCK caused a strong activation of p125 focal adhesion kinase (p125(FAK)) and a marked reorganisation of the actin cytoskeleton.
Inhibitory mechanisms triggered by low-affinity CCK-1 receptors interrupt enzyme secretion from pancreatic acini at late stages in the signal transduction cascades since bombesin receptor binding and early signalling events remained intact after CCK preincubation. A reorganisation of the actin cytoskeleton is suggested to be the mechanism by which low-affinity CCK-1 receptors actively interrupt enzyme secretion stimulated by other receptors.
刺激胰腺腺泡上的低亲和力CCK-1受体可导致酶分泌受到抑制。我们研究了信号转导机制，以确定分泌减少的潜在原因。
用CCK、CCK-JMV-180和蛙皮素进行的共刺激实验显示，低亲和力CCK-1受体会抑制蛙皮素刺激的酶分泌。CCK预孵育后，125I-胃泌素释放肽（蛙皮素的哺乳动物类似物）与腺泡的结合未发生改变。腺泡用高浓度CCK短暂预孵育后，细胞内钙对蛙皮素仍有反应。与浓度为10(-10) M或更低的蛙皮素或CCK不同，高浓度CCK会强烈激活p125粘着斑激酶（p125(FAK)）并显著重组肌动蛋白细胞骨架。
低亲和力CCK-1受体触发的抑制机制在信号转导级联反应的后期中断胰腺腺泡的酶分泌，因为CCK预孵育后蛙皮素受体结合和早期信号事件保持完整。肌动蛋白细胞骨架的重组被认为是低亲和力CCK-1受体主动中断其他受体刺激的酶分泌的机制。
