Moses D F, González S, Ortí E, De Nicola A F
Laboratorio de Bioquímica Neuroendócrina, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Brain Res. 1989 Mar 6;481(2):317-24. doi: 10.1016/0006-8993(89)90809-3.
The central nervous system contains two classes of corticoid receptors, named types I and II following terminology accepted for the kidney. Phenotypically, type I sites are differentiated into a corticosterone (CORT)-preferring species (Ia) and a mineralocorticoid receptor (Ib). These populations were tentatively compared in the spinal cord and hippocampus. Using [3H]dexamethasone (DEX) and selective blockage of sites, we have observed that type II receptors were comparable in both tissues, while Ia was almost exclusive of the hippocampus. Saturation analysis using [3H]DEX demonstrated that type Ia was a low affinity receptor (Kd approximately equal to 2-5 nM) while type II was a higher affinity site (KdII less than KdI). Using [3H]CORT, or [3H]aldosterone (ALDO), as ligand, preferential labeling of type I sites was achieved, always showing higher concentrations in the hippocampus. Therefore, [3H]DEX seems a ligand of choice to visualize types Ia and II receptors. Another difference noted between the spinal cord and hippocampus, pertained to the sensitivity towards the enzyme RNAse A, which increases heat-induced transformation of the bound receptor, according to the results of DNA cellulose affinity chromatography. In these experiments, type I sites of both spinal cord and hippocampus, plus type II of hippocampus, showed sensitivity toward the enzyme, whereas type II of the spinal cord was refractory to RNAse A enhancement of transformation. These results indicate that the dynamics of transformation is different among receptors showing similar affinity and competition, suggesting further heterogeneity due to receptors themselves, or to tissue factors regulating their biochemical properties.
中枢神经系统含有两类皮质激素受体，按照肾脏领域所接受的术语，分别命名为I型和II型。从表型上看，I型位点可分为偏好皮质酮（CORT）的亚型（Ia）和盐皮质激素受体（Ib）。我们初步比较了脊髓和海马体中的这些受体群体。通过使用[3H]地塞米松（DEX）并选择性阻断受体位点，我们观察到II型受体在这两种组织中情况相似，而Ia型受体几乎仅存在于海马体中。使用[3H]DEX进行的饱和分析表明，Ia型是低亲和力受体（解离常数Kd约为2 - 5 nM），而II型是高亲和力位点（KdII小于KdI）。使用[3H]CORT或[3H]醛固酮（ALDO）作为配体时，可实现对I型位点的优先标记，且总是显示出海马体中的浓度更高。因此，[3H]DEX似乎是可视化Ia型和II型受体的理想配体。根据DNA纤维素亲和色谱的结果，脊髓和海马体之间另一个值得注意的差异与对核糖核酸酶A（RNAse A）的敏感性有关，该酶会增加结合受体的热诱导转化。在这些实验中，脊髓和海马体的I型位点以及海马体的II型位点对该酶敏感，而脊髓的II型位点对RNAse A增强的转化具有抗性。这些结果表明，在显示相似亲和力和竞争性的受体中，转化动力学是不同的，这表明由于受体本身或调节其生化特性的组织因子，可能存在进一步的异质性。
