二腺苷多磷酸刺激离体大鼠近端肾小管的糖异生作用。
Diadenosine polyphosphate-stimulated gluconeogenesis in isolated rat proximal tubules.
作者信息
Edgecombe M, Craddock H S, Smith D C, McLennan A G, Fisher M J
机构信息
Department of Biochemistry, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, UK.
出版信息
Biochem J. 1997 Apr 15;323 ( Pt 2)(Pt 2):451-6. doi: 10.1042/bj3230451.
Diadenosine polyphosphates released into the extracellular environment influence a variety of metabolic and other cellular activities in a wide range of target tissues. Here we have studied the impact of these novel nucleotides on gluconeogenesis in isolated rat proximal tubules. Gluconeogenesis was stimulated following exposure of isolated proximal tubules to a range of adenine-containing nucleotides including ADP, ATP, Ap3A, Ap4A, Ap5A and Ap6A. The concentration-dependence of ATP-, Ap3A- and Ap4A-mediated stimulation of gluconeogenesis was similar and was consistent with a role for these agents in the physiological control of renal metabolism. Nucleotide-stimulated gluconeogenesis was diminished in the presence of agents that interfere with phospholipase C activation or intracellular Ca2+ metabolism, indicative of a role for polyphosphoinositide-mediated Ca2+ mobilization in the mechanism of action of ATP, Ap3A and Ap4A. The characteristics of binding of [2-3H]Ap4A to renal plasma-membrane preparations suggest that Ap4A mediates its effects on proximal tubule gluconeogenesis via interaction with P2y-like purinoceptor(s) also recognized by extracellular ATP.
释放到细胞外环境中的二腺苷多磷酸在多种靶组织中影响多种代谢及其他细胞活动。在此，我们研究了这些新型核苷酸对分离的大鼠近端小管糖异生的影响。将分离的近端小管暴露于一系列含腺嘌呤的核苷酸（包括ADP、ATP、Ap3A、Ap4A、Ap5A和Ap6A）后，糖异生受到刺激。ATP、Ap3A和Ap4A介导的糖异生刺激的浓度依赖性相似，且与这些物质在肾脏代谢生理控制中的作用一致。在存在干扰磷脂酶C激活或细胞内Ca2+代谢的物质时，核苷酸刺激的糖异生减弱，这表明多磷酸肌醇介导的Ca2+动员在ATP、Ap3A和Ap4A的作用机制中发挥作用。[2-3H]Ap4A与肾血浆膜制剂结合的特性表明，Ap4A通过与细胞外ATP也识别的P2y样嘌呤受体相互作用来介导其对近端小管糖异生的影响。
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