Wisner J R, McLaughlin R E, Rich K A, Ozawa S, Renner I G
Department of Medicine, University of Southern California School of Medicine, Los Angeles.
Gastroenterology. 1988 Jan;94(1):109-13. doi: 10.1016/0016-5085(88)90617-8.
Chronic feeding of rats with camostate results in pancreatic hypertrophy or hyperplasia, or both. Previous studies suggest that this effect of camostate occurs via an increase in endogenous cholecystokinin due to an enteral feedback mechanism involving the inhibition of trypsin in the duodenum. Studies employing proglumide, a weak and relatively nonspecific cholecystokinin antagonist, have failed to fully abolish camostate-induced pancreas growth. We examined the effects of L-364,718, a new and highly potent cholecystokinin receptor antagonist, on camostate-induced pancreas growth in rats. The pancreas weights and the concentrations of ribonucleic acid, protein, and chymotrypsinogen in the pancreas of rats treated with camostate alone were significantly elevated over those of controls. These effects of camostate were completely abolished in rats treated with camostate + L-364,718. The pancreas weights and the concentrations of deoxyribonucleic acid and ribonucleic acid in the pancreas of rats treated with L-364,718 alone were significantly lower than values in control rats. These data indicate that camostate-induced pancreas growth in rats appears to be dependent on the actions of endogenous cholecystokinin and that cholecystokinin may play a role in the maintenance of pancreatic growth in normal rats.
长期给大鼠喂食卡莫司他会导致胰腺肥大或增生，或两者皆有。先前的研究表明，卡莫司他的这种作用是通过肠内反馈机制导致内源性胆囊收缩素增加而发生的，该机制涉及十二指肠中胰蛋白酶的抑制。使用丙谷胺（一种弱且相对非特异性的胆囊收缩素拮抗剂）的研究未能完全消除卡莫司他诱导的胰腺生长。我们研究了新型高效胆囊收缩素受体拮抗剂L-364,718对卡莫司他诱导的大鼠胰腺生长的影响。单独用卡莫司他治疗的大鼠胰腺重量以及胰腺中核糖核酸、蛋白质和胰凝乳蛋白酶原的浓度均显著高于对照组。在接受卡莫司他+L-364,718治疗的大鼠中，卡莫司他的这些作用完全被消除。单独用L-364,718治疗的大鼠胰腺重量以及胰腺中脱氧核糖核酸和核糖核酸的浓度显著低于对照大鼠的值。这些数据表明，卡莫司他诱导的大鼠胰腺生长似乎依赖于内源性胆囊收缩素的作用，并且胆囊收缩素可能在正常大鼠胰腺生长的维持中起作用。
