Gualberto A, Conde M, Sobrino F
Dept. de Bioquímica Médica y Biología Molecular, Facultad de Medicina, Universidad de Sevilla, Spain.
Biochim Biophys Acta. 1994 Mar 31;1221(2):199-205. doi: 10.1016/0167-4889(94)90014-0.
Effects of phenylephrine, oxytocin and angiotensin on fructose 2,6-bisphosphate (Fru 2,6-P2) content and glycolytic parameters were studied in incubated thymus lymphocytes. These hormones modified Fru 2,6-P2 content dependent upon the energetic status of the cells. In non-preincubated thymus lymphocytes (with relatively high levels of glycogen and ATP), phenylephrine, oxytocin and angiotensin depressed Fru 2,6-P2 content in a dose-dependent manner. The opposite was found when the cells were preincubated for 2 h without substrates (low levels of ATP and glycogen). Changes in lactate release were less evident, but significant. Phenylephrine did not modify the maximal activities of phosphofructokinase (PFK)-1 or PFK-2. However, both submaximal PFK-1 and PFK-2 activities were inhibited by phenylephrine, and the response to exogenous Fru 2,6-P2 on PFK-1 was also altered. The activities of Fru 1,6-P2 and pyruvate kinase were not modified by phenylephrine or A23187 treatment. Simultaneous presence of Cyclosporin A (CsA), an immunosuppressive drug, antagonizes the alpha-adrenergic effect on Fru 2,6-P2 content. CsA alone did not alter basal levels of ATP, hexose phosphate or Fru 2,6-P2, and its opposing effect to alpha-agonist was dose-dependent. CsA cannot change the positive action of PMA or the negative action of A23187 on Fru 2,6-P2 content. The present data suggest that CsA acts prior to calcium liberation and protein kinase C activation. Different possible molecular models are discussed.
在孵育的胸腺淋巴细胞中研究了去氧肾上腺素、催产素和血管紧张素对果糖2,6-二磷酸（Fru 2,6-P2）含量及糖酵解参数的影响。这些激素根据细胞的能量状态改变Fru 2,6-P2含量。在未预孵育的胸腺淋巴细胞中（糖原和ATP水平相对较高），去氧肾上腺素、催产素和血管紧张素以剂量依赖的方式降低Fru 2,6-P2含量。当细胞在无底物的情况下预孵育2小时（ATP和糖原水平较低）时，结果则相反。乳酸释放的变化不太明显，但具有显著性。去氧肾上腺素未改变磷酸果糖激酶（PFK）-1或PFK-2的最大活性。然而，去氧肾上腺素抑制了亚最大PFK-1和PFK-2活性，并且对PFK-1对外源性Fru 2,6-P2的反应也产生了改变。Fru 1,6-P2和丙酮酸激酶的活性未因去氧肾上腺素或A23187处理而改变。免疫抑制药物环孢素A（CsA）的同时存在可拮抗α-肾上腺素能对Fru 2,6-P2含量的影响。单独使用CsA不会改变ATP、磷酸己糖或Fru 2,6-P2的基础水平，并且其对α-激动剂的拮抗作用呈剂量依赖性。CsA不能改变佛波酯（PMA）的正向作用或A23187对Fru 2,6-P2含量的负向作用。目前的数据表明，CsA在钙释放和蛋白激酶C激活之前起作用。文中讨论了不同的可能分子模型。
