HIGH-AFFINITY BINDING OF CORTICOSTERONE TO MAMMALIAN NEURONAL MEMBRANES - POSSIBLE ROLE OF CORTICOSTEROID-BINDING GLOBULIN

The signal transduction mechanisms mediating rapid steroid actions are poorly understood. To characterize corticosteroid interaction with ne uronal membranes in a species with rapid behavioral responses to corti costerone, we examined [H-3]corticosterone binding to membranes prepar ed from prairie vole brains. At 22 degrees C, the rates of association and dissociation of [H-3]corticosterone with well-washed synaptosomal membranes were very rapid. Specific binding was characterized by high affinity (K-d = 6.01 nM) and low density (B-max = 63.1 fmol/mg protei n). The binding sites were highly specific for naturally occurring glu cocorticoids and the density of binding sites appeared to vary by neur oanatomical region. Unlike most G-protein-coupled receptors, the high- affinity binding of [H-3]corticosterone to vole brain membranes was un affected by the addition of Mg2+ or guanyl nucleotides. Surprisingly, saline perfusion of vole brains before tissue homogenization greatly r educed high-affinity binding. In addition, the affinity and specificit y of corticosteroid binding sites were similar in vole neuronal membra nes and vole plasma. These data suggest that corticosteroid binding gl obulins may facilitate [H-3]corticosterone binding to neuronal membran es. However, the addition of blood to perfused brains before homogeniz ation did not restore high-affinity binding, so the role of plasma bin ding globulins is unclear. Whether these binding phenomena represent a technical artifact or a regulatory mechanism for corticosteroid actio n has yet to be determined. (C) 1997 Elsevier Science Ltd.