title: 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.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Gomar
authors.forename: B
authors.initials: B
authors.lastname: Fernández
authors.forename: C M
authors.initials: CM
authors.lastname: Del Aguila
authors.forename: J L
authors.initials: JL
authors.lastname: Castillo
authors.forename: G
authors.initials: G
authors.lastname: Escames
authors.forename: D
authors.initials: D
authors.lastname: Acuña-Castroviejo
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005445:Flunitrazepam / Q000378:metabolism; D007016:Hypophysectomy; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010902:Pituitary Gland / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
chemical_list: D010446:Peptide Fragments; D011963:Receptors, GABA-A; C026384:ACTH (1-4); C011393:ACTH (1-10); D005445:Flunitrazepam; D000324:Adrenocorticotropic Hormone; D008550:Melatonin