Gomez-Angelats M, del Santo B, Mercader J, Ferrer-Martinez A, Felipe A, Casado J, Pastor-Anglada M
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Spain.
Biochem J. 1996 Feb 1;313 ( Pt 3)(Pt 3):915-20. doi: 10.1042/bj3130915.
Na(+)-dependent uridine uptake is stimulated in isolated rat liver parenchymal cells by glucagon. This effect is transient, reaches maximum levels of stimulation 10 min after hormone addition, and is dose-dependent. Glucagon action can be mimicked by agents that are able to hyperpolarize the plasma membrane (e.g. monensin) and by dibutyryl cyclic AMP. The effects triggered by glucagon, monensin and dibutyryl cyclic AMP are not additive, suggesting a common mechanism of action. 8-(4-Chloro-phenylthio)adenosine 3':5'-cyclic monophosphate (PCT), a cyclic AMP analogue but also a nucleoside analogue, markedly stimulates Na(+)-dependent uridine uptake in an additive manner to that triggered by monensin, similarly to the effect described for nitrobenzylthioinosine. Considering the roles reported for nucleosides in liver metabolism, the use of PCT as a cyclic AMP analogue should be precluded. Insulin is also about to up-regulate Na(+)-dependent uridine uptake by a mechanism which involves a stable induction of this transport activity at the plasma-membrane level. This is consistent with a mechanism involving synthesis and insertion of more carriers into the plasma membrane. It is concluded that the recently characterized hepatic concentrative nucleoside transporter is under short-term hormonal regulation by glucagon, through mechanisms which involve membrane hyperpolarization, and under long-term control by insulin. This is the first report showing hormonal modulation of the hepatic concentrative nucleoside transporter.
在分离的大鼠肝实质细胞中，胰高血糖素可刺激钠离子依赖性尿苷摄取。这种作用是短暂的，在添加激素后10分钟达到最大刺激水平，且呈剂量依赖性。能够使质膜超极化的试剂（如莫能菌素）以及二丁酰环磷腺苷可模拟胰高血糖素的作用。胰高血糖素、莫能菌素和二丁酰环磷腺苷引发的效应并非相加性的，这表明它们具有共同的作用机制。8-（4-氯苯硫基）腺苷3':5'-环一磷酸（PCT），一种环磷腺苷类似物但也是核苷类似物，与硝基苄硫基肌苷所描述的效应类似，以与莫能菌素引发的效应相加的方式显著刺激钠离子依赖性尿苷摄取。考虑到核苷在肝脏代谢中所报道的作用，应避免将PCT用作环磷腺苷类似物。胰岛素也即将通过一种机制上调钠离子依赖性尿苷摄取，该机制涉及在质膜水平稳定诱导这种转运活性。这与一种涉及合成并将更多载体插入质膜的机制相一致。得出的结论是，最近鉴定出的肝脏浓缩核苷转运体受到胰高血糖素的短期激素调节，其机制涉及膜超极化，并且受到胰岛素的长期控制。这是首次报道显示肝脏浓缩核苷转运体的激素调节作用。
