Otsuki M, Williams J A
Am J Physiol. 1982 Oct;243(4):G285-90. doi: 10.1152/ajpgi.1982.243.4.G285.
Isolated rat pancreatic acini were treated with cycloheximide and amylase release was measured. This agent increased the sensitivity to both synthetic octapeptide of cholecystokinin (CCK8) and carbamylcholine, the major secretagogues known to utilize Ca2+ as a second messenger. The mechanism of the cycloheximide effect was via inhibition of protein synthesis, as indicated by the following: 1) the concentration of cycloheximide used inhibited leucine incorporation by greater than 90%; 2) this effect was not instantaneous but increased up to a 2-h pretreatment; and 3) a similar effect was obtained with puromycin, a chemically different inhibitor of protein synthesis. Cycloheximide acted on the steps by which secretagogues mobilize cellular Ca2+ because the dose-response curve for 45Ca2+ efflux was shifted to the same extent as that for amylase release, whereas the dose-response curve for amylase release induced by the Ca2+ ionophore A23187 was not altered. The results suggest, therefore, that a rapidly turning-over protein present in pancreatic acinar cells exerts an inhibitory influence on Ca2+ mobilization by secretagogues.
将分离出的大鼠胰腺腺泡用放线菌酮处理，并测定淀粉酶释放量。该试剂增加了对胆囊收缩素（CCK8）的合成八肽和氨甲酰胆碱的敏感性，这两种主要促分泌剂已知利用Ca2+作为第二信使。放线菌酮的作用机制是通过抑制蛋白质合成，如下所示：1）所用放线菌酮的浓度抑制亮氨酸掺入超过90%；2）这种作用不是即时的，而是在长达2小时的预处理后增加；3）用嘌呤霉素（一种化学结构不同的蛋白质合成抑制剂）也获得了类似的效果。放线菌酮作用于促分泌剂动员细胞Ca2+的步骤，因为45Ca2+外流的剂量反应曲线与淀粉酶释放的剂量反应曲线移动到相同程度，而Ca2+离子载体A23187诱导的淀粉酶释放的剂量反应曲线没有改变。因此，结果表明，胰腺腺泡细胞中一种快速周转的蛋白质对促分泌剂的Ca2+动员施加抑制性影响。
