Brachet P, Quemener V, Havouis R, Tomé D, Moulinoux J P
Unité de Nutrition Humaine et Physiologie Intestinale de l'I.N.R.A., Faculté de Pharmacie, Paris, France.
Biochim Biophys Acta. 1994 Nov 29;1227(3):161-70. doi: 10.1016/0925-4439(94)90090-6.
Intestinal absorption of putrescine and tissue metabolism of polyamines were investigated in rats grafted with the rapidly growing Mat-Lylu prostatic tumor. These animals exhibited a dramatic 21% decrease in weight and protein, but not DNA, content of their intestinal mucosa, relative to healthy rats reared under similarly controlled nutritional conditions. No significant variation in the specific activities of intestinal brush-border membrane enzymes was observed, however, suggesting a comparable differentiation state of intestinal cells exists in both groups. Putrescine uptake by brush-border membrane vesicles prepared from cancerous or healthy rat intestine was a time dependent process at 25 degrees C. Equilibrium uptake was much greater than could be explained by equilibration of the vesicle space with putrescine, indicating that the diamine was bound to membrane sites. Kinetics of putrescine uptake at 2 min revealed that the process involves two components, a saturable Michaelis-Menten carrier and passive diffusion. With respect to the kinetic parameters of putrescine transport, no significant changes were observed between the tumor-bearing and the control rats. After correction for nonspecific binding to the membranes, putrescine accumulation at equilibrium (75 min) was concentration-dependent and fit a single-site saturable model. Maximum accumulation of the diamine at equilibrium (Bmax) was increased by more than 46% in the cancerous rats relative to the controls, but the dissociation constant (Kd) was unchanged. Efflux of putrescine from the vesicles was slightly slower in the tumor-bearing group, but the differences were generally not significant. No change was observed with respect to the specific activity of ornithine decarboxylase and the concentration of polyamines in the intestinal mucosa. In Mat-Lylu grafted rats fed a standard diet supplemented with [14C]putrescine, about 19% of body radioactivity was recovered in the tumor within 24 h. This was concomitant with a decrease in the percentage of radioactivity retained in the intestinal, renal and hepatic tissues, relative to that retained in the same tissues of healthy rats. Our findings indicate that the presence of the tumor evolves an adaptive response in the small intestine of the rat, involving an increased capacity of the brush-border membrane to accumulate putrescine.
在移植了快速生长的Mat-Lylu前列腺肿瘤的大鼠中，研究了腐胺的肠道吸收和多胺的组织代谢。相对于在类似控制的营养条件下饲养的健康大鼠，这些动物的体重和肠道黏膜蛋白质含量显著下降了21%，但DNA含量没有下降。然而，未观察到肠道刷状缘膜酶比活性的显著变化，这表明两组中肠道细胞的分化状态相当。在25℃下，从癌性或健康大鼠肠道制备的刷状缘膜囊泡对腐胺的摄取是一个时间依赖性过程。平衡摄取量远大于囊泡空间与腐胺平衡所能解释的量，表明二胺与膜位点结合。2分钟时腐胺摄取的动力学表明，该过程涉及两个成分，一个是可饱和的米氏载体和被动扩散。关于腐胺转运的动力学参数，在荷瘤大鼠和对照大鼠之间未观察到显著变化。校正与膜的非特异性结合后，平衡（75分钟）时腐胺的积累呈浓度依赖性，符合单位点可饱和模型。相对于对照，癌性大鼠中平衡时二胺的最大积累量（Bmax）增加了46%以上，但解离常数（Kd）未改变。荷瘤组中腐胺从囊泡中的流出略慢，但差异通常不显著。肠道黏膜中鸟氨酸脱羧酶的比活性和多胺浓度未观察到变化。在喂食补充了[14C]腐胺的标准饮食的Mat-Lylu移植大鼠中，24小时内肿瘤中回收了约19%的全身放射性。这伴随着肠道、肾脏和肝脏组织中保留的放射性百分比相对于健康大鼠相同组织中保留的放射性百分比的下降。我们的研究结果表明，肿瘤的存在使大鼠小肠产生适应性反应，包括刷状缘膜积累腐胺的能力增加。
