Camello P J, Wisdom D, Singh J, Francis L P, Salido G M
Department of Physiology, Faculty of Veterinary Sciences, University of Extremadura, Caceres, Spain.
Arch Int Physiol Biochim Biophys. 1993 Mar-Apr;101(2):133-9. doi: 10.3109/13813459309008882.
In anaesthetized rats, interaction between either vagal stimulation or acetylcholine (ACh) and the phorbol ester, 12-0-tetradecanoylphorbol-13-acetate (TPA) and staurosporine on pancreatic juice secretion have been investigated in vivo. In vitro, rat cytosolic free calcium concentration (Ca2+)i in pancreatic acini loaded with the fluorescent dye, Fura-2 acetoxymethyl ester (AM) have been analysed after the same modifications. In vivo, vagotomy caused a marked reduction in the rate of pancreatic juice flow, total protein output and amylase secretion compared to basal secretory parameters. Furthermore, bolus injection of either saline, TPA (10(-8) mol/kg b wt), staurosporine (10(-8) mol/kg b wt) or a combination of TPA and staurosporine (all 10(-8) mol/kg b wt) had no statistically significant effect on pancreatic juice flow, protein output and amylase secretion compared to vagotomy values. Electrical stimulation (E.S.) of vagues nerves resulted in marked and statistically significant (P < 0.05) increases in the rate of pancreatic juice flow, total protein output and amylase secretion in rats injected with either saline or staurosporine, compared to control values. In contrast, E.S. of the vagus nerves failed to enhance all secretory parameters in the presence of either TPA or a combination of TPA and staurosporine. In vitro, on isolated acini, ACh evoked dose dependent increases in (Ca2+)i. Pretreatment these acini with either TPA, staurosporine or a combination of TPA and staurosporine had no significant effect on the ACh-induced (Ca2+)i. These results indicate that TPA can decrease the secretory responses evoked by E.S. of the vagus nerves in the anaesthetized rat. This attenuation is not associated with either protein kinase C inhibition or the mobilization of the second messenger Ca2+ but possibly through activation of protein kinase C by TPA.
在麻醉大鼠体内，研究了迷走神经刺激或乙酰胆碱（ACh）与佛波酯、12-0-十四烷酰佛波醇-13-乙酸酯（TPA）和星形孢菌素对胰液分泌的相互作用。在体外，在用荧光染料Fura-2乙酰氧基甲酯（AM）加载的胰腺腺泡中，分析了大鼠胞质游离钙浓度（Ca2+）i在相同处理后的变化。在体内，与基础分泌参数相比，迷走神经切断术导致胰液流速、总蛋白输出量和淀粉酶分泌率显著降低。此外，与迷走神经切断术的值相比，推注生理盐水、TPA（10(-8)mol/kg体重）、星形孢菌素（10(-8)mol/kg体重）或TPA与星形孢菌素的组合（均为10(-8)mol/kg体重）对胰液流速、蛋白输出量和淀粉酶分泌没有统计学上的显著影响。对迷走神经进行电刺激（E.S.）导致注射生理盐水或星形孢菌素的大鼠的胰液流速、总蛋白输出量和淀粉酶分泌率显著且有统计学意义（P<0.05）增加，与对照值相比。相反，在存在TPA或TPA与星形孢菌素的组合的情况下，迷走神经的E.S.未能增强所有分泌参数。在体外，在分离的腺泡上，ACh引起（Ca2+）i的剂量依赖性增加。用TPA、星形孢菌素或TPA与星形孢菌素的组合对这些腺泡进行预处理对ACh诱导的（Ca2+）i没有显著影响。这些结果表明，TPA可以降低麻醉大鼠迷走神经电刺激引起的分泌反应。这种减弱与蛋白激酶C抑制或第二信使Ca2+的动员无关，但可能是通过TPA激活蛋白激酶C实现的。
