DNA synthesis was stimulated by primary (complete) mitogens such as epidermal growth factor (EGF) or transforming growth factor α (TGFα) in adult rat hepatocytes in primary culture. Addition of neuropeptide γ (10-9 M) to the hepatocyte culture amplified the stimulatory effect of EGF or TGFα by 5- to 6-fold. Neuropeptide γ-amplified DNA synthesis was observed in a dose-dependent manner with maximal effect at 10-9 to 10-7 M, although it effect was significantly observed at as low as 10-10 M. Neuropeptide γ by itself did not stimulate DNA synthesis in the absence of EGF. Amplification of DNA synthesis by neuropeptide γ was observed when hepatocytes were cultured in Williams' medium E, but not in Leibovitz L-15 medium, suggesting that culture medium enriched with nutrients is required for hepatocytes to respond fully to neuropeptide γ. Neuropeptide γ amplified DNA synthesis in hepatocytes from both normal rat and partially hepatectomized rat, although its effect was stronger in normal hepatocytes. Neuropeptide K or substance P which are translated from mRNAs of the same gene as that of neuropeptide γ did not have amplifying effect on DNA synthesis at all concentrations tested even in the presence of EGF. Insulin (500 ng/ml), one of the secondary mitogens (comitogens), interacted additively with EGF. When EGF was present in the culture medium, neuropeptide γ interacted additively with insulin as well as EGF. From these results, neuropeptide γ can be regarded as a new secondary mitogen.
|Number of pages||8|
|Publication status||Published - 1993|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)