Löser C, Fölsch U R
Department of Internal Medicine, Christian Albrecht University of Kiel, FRG.
Digestion. 1993;54(4):213-23. doi: 10.1159/000201040.
Aim of the present study was to evaluate the relevance of various intracellular regulatory mechanisms of polyamine metabolism in normal and camostate (FOY 305)-induced pancreatic growth in rats. Furthermore it was investigated whether the simultaneous inhibition of the polyamine interconversion pathway by the potent polyamine oxidase inhibitor MDL-72527 together with the ornithine decarboxylase (ODC) inhibitor alpha-difluoromethylornithine (DFMO) is able to enhance and prolong the only initial and transient inhibitory effects of DFMO on camostate-induced pancreatic growth. Simultaneous administration of DFMO and MDL-72527 resulted in a significant inhibition of the camostate-induced increases in pancreatic putrescine, ODC and DNA over 5 days, while the initial significant inhibition of pancreatic weight, protein content, DNA-polymerase and especially spermidine was absent after 5 days and spermine as well as N1-acetylspermidine were even increased. Diamine oxidase (DAO) activity in pancreas is very low and the potent DAO inhibitor aminoguanidine failed to alter any of the measured parameters except DAO. Therefore, oxidative degradation of putrescine by DAO--which is essential in the gut--is irrelevant in the pancreas. Simultaneous inhibition of the pancreatic polyamine interconversion pathway extended the initial inhibitory effects of DFMO only slightly and failed to exert a potent long-lasting inhibitory effect on spermidine and pancreatic growth.
本研究的目的是评估多胺代谢的各种细胞内调节机制在正常大鼠以及喜美康（FOY 305）诱导的大鼠胰腺生长中的相关性。此外，还研究了强效多胺氧化酶抑制剂MDL-72527与鸟氨酸脱羧酶（ODC）抑制剂α-二氟甲基鸟氨酸（DFMO）同时抑制多胺相互转化途径是否能够增强并延长DFMO对喜美康诱导的胰腺生长仅有的初始短暂抑制作用。DFMO和MDL-72527同时给药导致在5天内对喜美康诱导的胰腺腐胺、ODC和DNA增加有显著抑制作用，而5天后胰腺重量、蛋白质含量、DNA聚合酶尤其是亚精胺的初始显著抑制作用消失，精胺以及N1-乙酰亚精胺甚至增加。胰腺中二胺氧化酶（DAO）活性非常低，强效DAO抑制剂氨基胍除了对DAO外未能改变任何测量参数。因此，DAO对腐胺的氧化降解（这在肠道中至关重要）在胰腺中无关紧要。同时抑制胰腺多胺相互转化途径仅略微延长了DFMO的初始抑制作用，并且未能对亚精胺和胰腺生长产生强效持久的抑制作用。
