Schmidt W E, Choudhury A R, Siegel E G, Löser C, Conlon J M, Fölsch U R, Creutzfeldt W
Department of Medicine, Georg-August-University of Göttingen, F.R.G.
Regul Pept. 1989 Jan;24(1):67-79. doi: 10.1016/0167-0115(89)90212-7.
The present study investigates the inhibitory effect of the novel potent benzodiazepine-related CCK-antagonist L-364,718 on pancreatic growth in the rat induced by chronic administration of caerulein and bombesin-like peptides. Caerulein, injected s.c. twice daily at a dose of 1 microgram/kg body weight, and bombesin (10 micrograms/kg) induced a similar increase (1.5-3-fold) in pancreatic wet weight, total protein, amylase, trypsin, putrescine and spermidine content after 14 days of treatment. Growth induced by caerulein showed a significant increase in total DNA content suggesting cellular hyperplasia, whereas bombesin-like peptides led to cellular hypertrophy. In comparison to bombesin the decapeptide neuromedin C (10 micrograms/kg) was found to be 30-50% less potent. In the same dose range, neuromedin B and the tachykinins neurokinin A and B, all structurally related to bombesin, had no significant trophic effect on the rat pancreas. Administration of the CCK-antagonist L-364,718 twice daily at a dose of 0.1 mg/kg or at 1.0 mg/kg, either s.c. or orally, led dose-dependently to a near-complete inhibition of the caerulein-induced trophic effect. In contrast, L-364,718 administered at identical dosages, did not affect pancreatic hypertrophy induced by bombesin and neuromedin C. It is concluded that both peptides mediate their effect on the rat pancreas directly and not via release of endogenous cholecystokinin. Tachykinins are not involved in the regulation of pancreatic growth. Caerulein- and bombesin-like peptides have comparable effects on the stimulation of protein and polyamine synthesis.
本研究调查了新型强效苯二氮䓬类相关胆囊收缩素拮抗剂L-364,718对大鼠胰腺生长的抑制作用，该生长由长期给予蛙皮素和蛙皮素样肽诱导。以1微克/千克体重的剂量每天皮下注射两次蛙皮素，以及给予蛙皮素（10微克/千克），在治疗14天后可诱导胰腺湿重、总蛋白、淀粉酶、胰蛋白酶、腐胺和亚精胺含量出现相似的增加（1.5至3倍）。蛙皮素诱导的生长表现为总DNA含量显著增加，提示细胞增生，而蛙皮素样肽导致细胞肥大。与蛙皮素相比，发现十肽神经介素C（10微克/千克）的效力低30%至50%。在相同剂量范围内，与蛙皮素结构相关的神经介素B以及速激肽神经激肽A和B对大鼠胰腺没有显著的营养作用。以0.1毫克/千克或1.0毫克/千克的剂量每天皮下注射或口服CCK拮抗剂L-364,718，剂量依赖性地导致对蛙皮素诱导的营养作用的近乎完全抑制。相比之下，以相同剂量给药的L-364,718并不影响由蛙皮素和神经介素C诱导的胰腺肥大。得出的结论是，这两种肽对大鼠胰腺的作用是直接介导的，而非通过内源性胆囊收缩素的释放介导。速激肽不参与胰腺生长的调节。蛙皮素和蛙皮素样肽对蛋白质和多胺合成的刺激作用相当。
