Interactions of ACTH4-10 and ACTH1-24 with L-[3H]glutamate binding sites and GABA/benzodiazepine/picrotoxin receptor complexes in vitro.
The effects of ACTH4-10 and ACTH1-24 on L-[3H]glutamate (Glu) binding sites and GABA/benzodiazepine/picrotoxin receptor complexes in vitro were investigated. ACTH4-10 and ACTH1-24 inhibited [3H] Glu and [3H] muscimol binding concentration-dependently, while [3H] flunitrazepam (FNP) and [35S] t-butylbicyclophosphorothionate (TBPS) binding were not affected. These ACTH fragments also inhibited GABA-stimulated [3H] FNP binding. These results suggest that ACTH and its fragments may act as anticonvulsants by antagonizing glutamate binding, their interaction with GABA-A sites may relate to the other central nervous effects of ACTH than the anticonvulsant activity.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002540:Cerebral Cortex / Q000378:metabolism*; D005445:Flunitrazepam / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D008297:Male; D009118:Muscimol / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005971:Glutamates; D010446:Peptide Fragments; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; C037480:picrotoxinin receptor; D009118:Muscimol; D018698:Glutamic Acid; D005445:Flunitrazepam; C037476:tert-butylbicyclophosphorothionate; D000324:Adrenocorticotropic Hormone; C011394:ACTH (4-10)