Participation of ACTH1-10 and ACTH4-10 on the melatonin modulation of benzodiazepine receptors in rat cerebral cortex.

Abstract

In this study, we examined the effect of intracerebroventricular (i.c.v) injection of melatonin and/or ACTH1-10 and ACTH4-10 on [3H]flunitrazepam binding sites in the cerebral cortex of hypophysectomized rats. Hypophysectomy increased the Bmax (maximum number of binding sites) of benzodiazepine (BNZ) receptors for at least 7 days after surgery, without changing KD (dissociation constant). The i.c.v. injection of melatonin to hypophysectomized rats significantly increased Bmax, whereas the same doses of melatonin were ineffective in sham-operated animals. In both cases, KD values were unchanged. The i.c.v. injection of ACTH1-10 to hypophysectomized animals significantly increased Bmax, an effect that was enhanced by simultaneous i.c.v. injection of ACTH1-10 + melatonin, reaching higher values of Bmax than the i.c.v. injection of these hormones individually. No significant changes in KD values were found after ACTH1-10 and/or melatonin administration. However, the i.c.v. injection of ACTH4-10 to hypophysectomized rats did not change Bmax, although it significantly increased KD values, indicating a decrease in the BNZ binding affinity. Melatonin injection counteracted this effect of ACTH4-10, returning KD to the control value. Moreover, although the lower dose of i.c.v. melatonin used, 10 ng, was unable to modify Bmax of BNZ binding in the ACTH4-10-injected group, the higher dose, 20 ng, significantly increased Bmax. The results suggest that these ACTH-derived peptides can modulate the effect of melatonin on brain benzodiazepine receptors.