Suwandito L, Leung Y K, Firmansyah A, Lebenthal E, Lee P C
Division of Gastroenterology, Children's Hospital of Buffalo, New York 14222.
Pancreas. 1989;4(4):459-63. doi: 10.1097/00006676-198908000-00011.
Vasoactive intestinal peptide (VIP) or 12-O-tetradecanoylphorbol-13-acetate (TPA) individually stimulated amylase release in dispersed rat pancreatic acini. Pretreatment of acini with TPA (10(-6) M) for 5 min at 37 degrees C potentiated their subsequent response to stimulation by VIP at a dose range of 10(-8)-10(-6) M in that the treated pancreatic acini released more amylase than could be accounted for by the additive effects of VIP or TPA acting individually. This potentiation effect of TPA was still evident when isobutyl methylxanthine was given together with VIP. Further, the maximal' dose-response curve to VIP shifted 2 log units to the left (3 x 10(-9) versus 3 x 10(-7) M). The TPA preincubation was found also to potentiate VIP-stimulated net increases in intracellular cyclic AMP (cAMP) levels. A close correlation existed between the net releases of amylase and the net increases in intracellular cAMP levels (r = 0.97). This suggested that TPA potentiated the response of rat pancreatic acini to VIP by modulating the cAMP system. The TPA as a potent activator of protein kinase C may act as a modulator of the adenylate cylase-cAMP system in rat pancreatic acini.
血管活性肠肽（VIP）或十四酰佛波醇乙酯（TPA）均可单独刺激分散的大鼠胰腺腺泡释放淀粉酶。在37℃下用TPA（10⁻⁶ M）预处理腺泡5分钟，可增强其随后对10⁻⁸ - 10⁻⁶ M剂量范围内VIP刺激的反应，即经处理的胰腺腺泡释放的淀粉酶量超过了VIP或TPA单独作用的累加效应所能解释的量。当异丁基甲基黄嘌呤与VIP一起给予时，TPA的这种增强作用仍然明显。此外，对VIP的最大剂量反应曲线向左移动了2个对数单位（3×10⁻⁹对3×10⁻⁷ M）。还发现TPA预孵育可增强VIP刺激引起的细胞内环磷酸腺苷（cAMP）水平的净增加。淀粉酶的净释放与细胞内cAMP水平的净增加之间存在密切相关性（r = 0.97）。这表明TPA通过调节cAMP系统增强了大鼠胰腺腺泡对VIP的反应。TPA作为蛋白激酶C的有效激活剂，可能在大鼠胰腺腺泡中充当腺苷酸环化酶 - cAMP系统的调节剂。
