Niederau C, Liddle R A, Williams J A, Grendell J H
Department of Medicine, University of Düsseldorf, FR Germany.
Gut. 1987;28 Suppl(Suppl):63-9. doi: 10.1136/gut.28.suppl.63.
The effects on pancreatic growth and plasma CCK concentration of chronic feeding of camostate (400 mg/kg day for 10 days), a potent inhibitor of serine proteases including trypsin, were assessed in the mouse. For comparison, the trophic effects of chronic exogenous administration of CCK octapeptide (sc injection of 1 microgram/kg day every eight hours for 10 days) were also studied. In addition, the effects of a proglumide-analogue CCK-receptor antagonist (CR1409) on the stimulatory actions of camostate feeding and chronic administration of exogenous CCK were studied. The effects of the combination of chronic camostate feeding and sc injections of CCK, the effects of acute camostate feeding, and the effects of the CCK-receptor antagonist given without camostate or CCK were also studied. The results show that chronic camostate feeding markedly increased CCK plasma concentrations eight-fold over control values, and that acute camostate feeding increased plasma concentration to four fold of control values. Correspondingly, chronic camostate feeding markedly increased pancreatic weight, protein and DNA content. Exogenous CCK-8 also had qualitatively similar, but quantitatively less potent stimulatory effects. The combination of camostate and CCK-8 resulted in an additive stimulatory effect. The trophic actions of exogenous and endogenous CCK grossly increased chymotrypsinogen content, but left amylase content unaffected. The CCK-receptor antagonist CR 1409 completely abolished the trophic effects of exogenous CCK and greatly inhibited the effects of chronic camostate feeding. The CCK antagonist decreased pancreatic weight, DNA and protein content compared to control values when given without any CCK or camostate. We conclude that the protease inhibitor camostate is a very strong release effector of CCK and exerts a powerful trophic effect on mouse pancreas which is probably mediated by CCK. Furthermore, physiological increases of CCK during feeding of regular chow appear to exert trophic effects on the exocrine pancreas.
在小鼠中评估了慢性给予抑肽酶（400毫克/千克/天，持续10天）对胰腺生长和血浆胆囊收缩素（CCK）浓度的影响，抑肽酶是包括胰蛋白酶在内的丝氨酸蛋白酶的强效抑制剂。为作比较，还研究了慢性外源性给予CCK八肽（每8小时皮下注射1微克/千克/天，持续10天）的营养作用。此外，研究了一种丙谷胺类似物CCK受体拮抗剂（CR1409）对抑肽酶喂养和慢性给予外源性CCK的刺激作用的影响。还研究了慢性抑肽酶喂养与皮下注射CCK联合的作用、急性抑肽酶喂养的作用以及在未给予抑肽酶或CCK的情况下给予CCK受体拮抗剂的作用。结果显示，慢性抑肽酶喂养使血浆CCK浓度比对照值显著增加了八倍，急性抑肽酶喂养使血浆浓度增加到对照值的四倍。相应地，慢性抑肽酶喂养显著增加了胰腺重量、蛋白质和DNA含量。外源性CCK - 8也有定性相似但定量上较弱的刺激作用。抑肽酶和CCK - 8联合产生了相加的刺激作用。外源性和内源性CCK的营养作用显著增加了糜蛋白酶原含量，但对淀粉酶含量没有影响。CCK受体拮抗剂CR1409完全消除了外源性CCK的营养作用，并大大抑制了慢性抑肽酶喂养的作用。与对照值相比，在未给予任何CCK或抑肽酶的情况下给予CCK拮抗剂会降低胰腺重量、DNA和蛋白质含量。我们得出结论，蛋白酶抑制剂抑肽酶是CCK的一种非常强的释放效应物，对小鼠胰腺具有强大的营养作用，这可能是由CCK介导的。此外，正常饮食喂养期间CCK的生理性增加似乎对外分泌胰腺发挥营养作用。
