Modulation of Rat Brain Cortical α‐Adrenoceptors by Treatment with Hydrocortisone for 10 Days

The role of glucocorticoids in the modulation of central α2‐receptor mechanisms was investigated by in vitro receptor binding studies. [ 3 H]Clonidine and [ 3 H]idazoxan were used as radioligands. The α2‐receptor subtypes and guanine nucleotide sensitivity were studied in homologue and heterologue displacement experiments following hydrocortisone treatment (25 mg/kg s.c.) for 10 days. High and low agonist affinity states of the α2‐receptor could be identified in 3 H‐antagonist‐agonist and 3 H‐agonist‐antagonist displacement experiments, which may correspond to different regulatory protein‐nucleotide associated forms of the receptor. In the presence of 10 μ M GTP, the high‐affinity binding was depressed. Following hydrocortisone treatment, there was no detectable change either in the affinity or the binding site concentration of clonidine in homologue displacement (“cold saturation”) experiments. The affinity of idazoxan, however, was depressed. The effect of GTP was similar to the controls in this experimental arrangement. In contrast, in heterologue binding studies the high‐affinity binding site was not demonstrable and the amount of low‐affinity binding increased following the hydrocortisone treatment. The high‐affinity site reappeared in the presence of GTP. The change in GTP sensitivity suggests that the nucleotide regulatory system may be involved in the action of adrenal steroids on central α2‐receptoral mechanisms.