Günther Rainer, Carstens Ove C, Schmidt Wolfgang E, Fölsch Ulrich R
Laboratory of Molecular Gastroenterology, 1st Department of Medicine, Christian-Albrechts-University of Kiel, Germany.
Pancreatology. 2003;3(1):47-54. doi: 10.1159/000069142.
CCK-8 and gastrin exert multiple effects in the gastrointestinal tract and the nervous system. Their actions are mediated via the G-protein coupled CCK-A and CCK-B receptors.
Rat pancreatic acinar tumor AR42J cells express both CCK receptor subtypes. This cell line was used to characterize the agonist-dependent regulation of CCK-A and CCK-B receptor gene expression.
CCK-8 (10 nM) or gastrin (10 nM) reduced CCK-A receptor mRNA expression to 56% and 53%, respectively 2 h after hormonal exposure. In contrast, the level of CCK-B receptor gene expression was upregulated to 157% and 153%, respectively. These effects are most probably linked to the CCK-B receptor in AR42J cells. The phorbolester PMA (100 nM), a protein kinase C activator, downregulated CCK-A receptor expression but did not affect CCK-B receptor gene transcription. Activation of protein kinase A by forskolin (10 microM) or Bt(2)cAMP (100 microM) is not involved in the transient regulation of CCK receptor mRNA expression. Both elevated CCK-B and decreased CCK-A receptor mRNA expression returned to basal levels 6 h after continuous stimulation.
These results demonstrate that CCK-A and CCK-B receptor mRNA levels are differentially regulated by their agonists via distinct signal transduction mechanisms in AR42J cells.
胆囊收缩素-8（CCK-8）和胃泌素在胃肠道和神经系统中发挥多种作用。它们的作用通过G蛋白偶联的CCK-A和CCK-B受体介导。
大鼠胰腺腺泡肿瘤AR42J细胞表达两种CCK受体亚型。该细胞系用于表征CCK-A和CCK-B受体基因表达的激动剂依赖性调节。
激素暴露2小时后，CCK-8（10 nM）或胃泌素（10 nM）分别将CCK-A受体mRNA表达降低至56%和53%。相比之下，CCK-B受体基因表达水平分别上调至157%和153%。这些效应很可能与AR42J细胞中的CCK-B受体有关。佛波酯PMA（100 nM），一种蛋白激酶C激活剂，下调CCK-A受体表达，但不影响CCK-B受体基因转录。福司可林（10 microM）或Bt(2)cAMP（100 microM）激活蛋白激酶A不参与CCK受体mRNA表达的瞬时调节。持续刺激6小时后，升高的CCK-B和降低的CCK-A受体mRNA表达均恢复至基础水平。
这些结果表明，在AR42J细胞中，CCK-A和CCK-B受体mRNA水平通过不同的信号转导机制受到其激动剂的差异调节。
