Kennedy M F, Tutton P J, Barkla D H
Br J Cancer. 1985 Sep;52(3):383-90. doi: 10.1038/bjc.1985.205.
Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour.
有证据表明，在正常和疾病状态下，肾上腺素能因子参与肠道上皮细胞增殖的调控。在本报告中，重点关注小鼠结肠化学诱导肿瘤过程中增殖细胞对胺需求的变化。通过静止动力学方法测量细胞增殖率。通过皮下注射二甲基肼（DMH）诱导肿瘤。一系列肾上腺素能受体激动剂和拮抗剂的结果表明，在正常结肠中存在α2肾上腺素能受体介导的兴奋作用，但在腺瘤和癌中存在α2肾上腺素能受体介导的抑制作用。另一方面，α1肾上腺素能受体在正常隐窝和腺瘤中具有抑制作用，而在癌中具有兴奋作用。β肾上腺素能受体在正常和经DMH处理的隐窝以及腺瘤中具有抑制作用，但在癌中没有。在经DMH处理的小鼠隐窝上皮中，可以识别出细胞增殖的两个区域，其调控因子不同。在致癌物暴露隐窝的上部区域，细胞增殖受α2肾上腺素能机制刺激，因此类似于正常隐窝的基部区域。相比之下，在这些隐窝的基部区域，细胞增殖受α1机制刺激，因此类似于恶性肿瘤。
