Hasegawa K, Carr B I
Department of Physiology, Dokkyo University School of Medicine, Tochigi, Japan.
Cell Struct Funct. 1993 Apr;18(2):105-10. doi: 10.1247/csf.18.105.
Epidermal growth factor and transforming growth factor alpha stimulated DNA synthesis in primary cultures of adult rat hepatocytes. In the presence of neurotensin, the stimulatory effect of epidermal growth factor or transforming growth factor alpha on DNA synthesis was enhanced 3- to 5-fold. Since neurotensin by itself did not stimulate DNA synthesis at all concentrations tested, enhancement of DNA synthesis by neurotensin is due to the amplification of the effect of epidermal growth factor or transforming growth factor alpha. The amplification by neurotensin was observed in a dose-dependent manner with a maximal effect at 10(-8)M, although its effect was significantly observed at as low as 10(-10) M. This neurotensin amplification of DNA synthesis was observed when hepatocytes were cultured in Williams' medium E, but not in Leibovitz L-15 medium, suggesting that minor components in the medium are required for hepatocytes to fully respond to neurotensin. Neurotensin-related peptides such as kinetensin or neuromedin-N did not have this amplifying effect on DNA synthesis at any concentration tested. From these results, neurotensin can be regarded as a new secondary mitogen.
表皮生长因子和转化生长因子α可刺激成年大鼠肝细胞原代培养物中的DNA合成。在神经降压素存在的情况下，表皮生长因子或转化生长因子α对DNA合成的刺激作用增强了3至5倍。由于在所有测试浓度下神经降压素本身都不刺激DNA合成，因此神经降压素对DNA合成的增强作用是由于表皮生长因子或转化生长因子α的作用放大所致。神经降压素的放大作用呈剂量依赖性，在10(-8)M时达到最大效应，尽管在低至10(-10)M时就可明显观察到其效应。当肝细胞在Williams' E培养基中培养时可观察到神经降压素对DNA合成的这种放大作用，但在Leibovitz L-15培养基中则未观察到，这表明培养基中的微量成分是肝细胞对神经降压素充分反应所必需的。在任何测试浓度下，诸如动素或神经介素-N等神经降压素相关肽对DNA合成均无这种放大作用。根据这些结果，神经降压素可被视为一种新的次级促有丝分裂原。
