EFFECT OF METHYLXANTHINES ON BINDING OF GLUCOCORTICOID RECEPTOR TO DNA-CELLULOSE AND NUCLEI
EFFECT OF METHYLXANTHINES ON BINDING OF GLUCOCORTICOID RECEPTOR TO DNA-CELLULOSE AND NUCLEI
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DOI：
10.1111/j.1432-1033.1978.tb12000.x
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发表时间：
1978-01-01
期刊：
影响因子：
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通讯作者：
LITWACK, G
中科院分区：
文献类型：
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作者：
CAKE, MH;LITWACK, G
茶碱的存在可在低温下大大增强大鼠肝胞质溶胶中[~ 3 H]地塞米松受体复合物与离体细胞核或DNA-纤维素的结合。氨茶碱和咖啡因可以模拟这种作用;罂粟碱和1-甲基-3-异丁基黄嘌呤，在抑制磷酸二酯酶的浓度下，对糖皮质激素受体与DNA的结合没有影响。当c[环]AMP水解已经完成时，可以加入茶碱，并且仍然增强DNA结合。茶碱的这种作用可能与其对cAMP水平的已知作用无关。甲基黄嘌呤的活化并不改变糖皮质激素受体复合物在蔗糖梯度中的沉降，但确实改变了pI，在这方面引起的变化类似于热活化时发生的变化。磷酸吡哆醛已显示出抑制热激活受体与DNA-纤维素的结合。磷酸吡哆醛也抑制茶碱处理的受体的DNA-纤维素结合。茶碱的存在还增强了[3 H]地塞米松与受体的结合速率，并增加了其对类固醇的表观亲和力。茶碱的作用可能是对某些胞质成分，也许是受体本身。在低温下暴露于茶碱导致的DNA结合增强也可以通过使用肾脏、胸腺和肝癌H35细胞的糖皮质激素受体来证明[大鼠肝癌]。
The binding of [3H]dexamethasone.cntdot.receptor complex from rat liver cytosol to isolated nuclei or DNA-cellulose can be greatly enhanced at low temperature by the presence of theophylline. Aminophylline and caffeine can mimic this effect; papaverine and 1-methyl-3-isobutylxanthine, at concentrations inhibitory to phosphodiesterase, are without effect on glucocorticoid receptor binding to DNA. Theophylline can be added when c[cyclic]AMP hydrolysis is already complete and still enhance DNA binding. This effect of theophylline is probably independent of its known effect on cAMP levels. Activation by methylxanthines does not alter the sedimentation of the glucocorticoid.cntdot.receptor complex in sucrose gradients but does alter the pI and in this respect brings about changes resembling those which occur on activation by heat. Pyridoxal phosphate has been shown to inhibit the binding of heat-activated receptor to DNA-cellulose. Pyridoxal phosphate also inhibits the DNA-cellulose binding of theophylline-treated receptor. The presence of theophylline also enhances the rate of binding of [3H]dexamethasone to the receptor and increases its apparent affinity for the steroid. The effect of theophylline is probably on some cytosolic component, perhaps the receptor itself. Enhanced DNA binding as a result of exposure to theophylline at low temperature can also be demonstrated using the glucocorticoid receptor of kidney, thymus and Reuber H35 cells [rat hepatoma].