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Induction of glucagon sensitivity in a transformed kidney cell line by prostaglandin E2 and its inhibition by epidermal growth factor.

机译:前列腺素E2在转化的肾细胞系中诱导胰高血糖素敏感性,并被表皮生长因子抑制。

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A model system using a transformed dog kidney cell line (Madin-Darby canine kidney), has been established for studying the process of differentiation. Glucagon responsiveness can be restored to these transformed cells by various differentiation inducers, including prostaglandin E2. Glucagon response was measured in terms of the ability of glucagon to stimulate cAMP production. Induction of glucagon sensitivity seems to be mediated by cAMP. The ability of various prostaglandin analogs to elevate the cAMP level correlates closely with their ability to induce glucagon sensitivity. In fact, 8-Br-cAMP is also a potent inducer. To define the nature of this cAMP-mediated process, we identified several inhibitors of this induction process. These differentiation inhibitors include serum, phorbol ester, and epidermal growth factor. These inhibitors do not have a direct effect on cAMP production by cells in the presence or absence of hormones. Furthermore, induction by 8-Br-cAMP is also inhibited by these agents. Therefore, the site of inhibition is located beyond the point of cAMP production. Possible interaction between cAMP- and epidermal growth factor-dependent phosphorylations is discussed.
机译:已经建立了使用转化的狗肾细胞系(Madin-Darby犬肾)的模型系统,用于研究分化过程。胰高血糖素反应性可以通过各种分化诱导剂(包括前列腺素E2)恢复到这些转化细胞。根据胰高血糖素刺激cAMP产生的能力来测量胰高血糖素应答。胰高血糖素敏感性的诱导似乎由cAMP介导。各种前列腺素类似物升高cAMP水平的能力与其诱导胰高血糖素敏感性的能力密切相关。实际上,8-Br-cAMP也是有效的诱导剂。为了定义这种cAMP介导的过程的性质,我们确定了该诱导过程的几种抑制剂。这些分化抑制剂包括血清,佛波酯和表皮生长因子。在存在或不存在激素的情况下,这些抑制剂对细胞产生的cAMP均无直接影响。此外,这些试剂还抑制了8-Br-cAMP的诱导。因此,抑制位点位于cAMP产生点之外。讨论了cAMP和表皮生长因子依赖性磷酸化之间可能的相互作用。

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