Ishigami A, Roth G S
Molecular Physiology and Genetics Section, National Institute on Aging, National Institute of Health, Francis Scott Key Medical Center, Baltimore, Maryland 21224.
J Cell Physiol. 1994 Feb;158(2):231-6. doi: 10.1002/jcp.1041580204.
We examined epinephrine- and isoproterenol-stimulated DNA synthesis in primary cultured hepatocytes from 6-, 12-, and 24-month-old rats. Epinephrine-stimulated DNA synthesis in 6-month-old rat hepatocytes began after 20 h and reached a maximum at 50 h. Similarly, isoproterenol-stimulated DNA synthesis in 6-month-old rat hepatocytes began after 10 h and reached a maximum at 45 h. In contrast, both epinephrine- and isoproterenol-stimulated DNA synthesis in 12- and 24-month-old rat hepatocytes were reduced approximately 40-60% and 80%, respectively, as compared to that at 6 months. Both epinephrine- and isoproterenol-stimulated DNA synthesis were strongly inhibited by the beta-adrenergic antagonist, propranolol, but not by the alpha 1-adrenergic antagonist, prazosin, or the alpha 2-adrenergic antagonist, yohimbine. However, in the presence of EGF, epinephrine-stimulated DNA synthesis activity was inhibited by prazosin but not by propranolol. These results indicate that stimulated DNA synthesis in rat hepatocytes declines with age and that there are two different pathways for epinephrine-stimulated DNA synthesis in the presence or absence of EGF.
我们检测了6个月、12个月和24个月大的大鼠原代培养肝细胞中肾上腺素和异丙肾上腺素刺激的DNA合成情况。肾上腺素刺激6个月大的大鼠肝细胞DNA合成在20小时后开始，并在50小时达到最大值。同样，异丙肾上腺素刺激6个月大的大鼠肝细胞DNA合成在10小时后开始，并在45小时达到最大值。相比之下，与6个月时相比，肾上腺素和异丙肾上腺素刺激12个月和24个月大的大鼠肝细胞DNA合成分别减少了约40%-60%和80%。肾上腺素和异丙肾上腺素刺激的DNA合成均受到β-肾上腺素能拮抗剂普萘洛尔的强烈抑制，但不受α1-肾上腺素能拮抗剂哌唑嗪或α2-肾上腺素能拮抗剂育亨宾的抑制。然而，在表皮生长因子（EGF）存在的情况下，肾上腺素刺激的DNA合成活性受到哌唑嗪的抑制，但不受普萘洛尔的抑制。这些结果表明，大鼠肝细胞中刺激的DNA合成随年龄增长而下降，并且在有或没有EGF的情况下，肾上腺素刺激的DNA合成存在两种不同的途径。
