McCurdy R E, Martinez R
Pediatr Res. 1981 Sep;15(9):1308-13. doi: 10.1203/00006450-198109000-00015.
Alterations in the pancreatic secretion of fluid and of enzymes in response to either pilocarpine (15 mg/kg) or an octapeptide of cholecystokinin (0.1 microgram/kg) have been found in rats that received daily injections of reserpine (0.5 mg/kg) for 7 days. During a 3-hr secretory period, significant reductions in the volume of pancreatic juice and in the total output of protein, amylase, and trypsin were observed in these animals. In the first hour of the secretory response, however, protease output was increased in the treated animals, particularly that of chymotrypsin, which was also increased in the longer secretory period following pilocarpine, but not cholecystokinin, stimulation. Zymogen granules isolated from the pancreas of the treated rats by differential centrifugation in a 0.3 M sucrose buffer had increased specific activities of the proteases when compared to those of untreated controls. Ultrastructurally, zymogen granules isolated from the pancreas of the treated rats showed changes in density, with bizonal and trizonal configurations being frequently observed, and had less distinct limiting membranes. In some, the membrane appeared broken at intervals, and there was granular material, presumably derived from the granule contents, lining the surface of the granule. It is concluded that pretreatment with reserpine inhibits fluid secretion and alters enzyme secretion in the rat exocrine pancreas. The latter effect is related to a nonparallel storage of amylase and proteases in the secretory granules induced by the drug treatment, probably through an action on protein synthesis or intracellular transport. An accumulation of proteases may lead to activation of these enzymes and to granule lysis. Inasmuch as the reserpine-treated rat has been proposed as an experimental model for cystic fibrosis, these findings are relevant in terms of possibly pathogenetic mechanisms in this disease.
在每日注射利血平（0.5毫克/千克），持续7天的大鼠中，发现其胰腺对毛果芸香碱（15毫克/千克）或一种胆囊收缩素八肽（0.1微克/千克）的液体和酶分泌发生了改变。在3小时的分泌期内，这些动物的胰液量以及蛋白质、淀粉酶和胰蛋白酶的总分泌量显著减少。然而，在分泌反应的第一个小时，经处理的动物中蛋白酶分泌增加，尤其是胰凝乳蛋白酶，在毛果芸香碱刺激后的较长分泌期内其分泌量也增加，但胆囊收缩素刺激后则不然。通过在0.3M蔗糖缓冲液中进行差速离心从经处理大鼠的胰腺中分离出的酶原颗粒，与未处理的对照相比，蛋白酶的比活性增加。超微结构上，从经处理大鼠的胰腺中分离出的酶原颗粒显示密度发生变化，经常观察到双区和三区结构，并且其限制膜不太清晰。在一些颗粒中，膜似乎间隔性破裂，并且有颗粒物质，推测源自颗粒内容物，衬于颗粒表面。结论是，利血平预处理可抑制大鼠外分泌胰腺的液体分泌并改变酶分泌。后一种效应与药物处理诱导的分泌颗粒中淀粉酶和蛋白酶的非平行储存有关，可能是通过对蛋白质合成或细胞内运输的作用。蛋白酶的积累可能导致这些酶的激活和颗粒溶解。鉴于利血平处理的大鼠已被提议作为囊性纤维化的实验模型，这些发现对于该疾病可能的发病机制具有重要意义。
