An analog of ACTH/MSH4-9, ORG-2766, reduces permeability of the blood-brain barrier.
Regional uptakes of a diffusion-limited substance, antipyrine, were compared to those of a highly diffusible substance, iodoantipyrine, in brains of conscious, unrestrained rats. The method included simultaneous measurements of regional cerebral blood flow. Within 10 min after intravenous injection of a behaviorally active analog of ACTH/MSL4-9, ORG-2766, the relative extraction of antipyrine was reduced in most regions of the brain, significantly in hypothalamus, hippocampus, parietal cortex and frontal cortex. The occipital cortex and brain stem were least affected. Since the flow of blood was not changed significantly in any region at this time, we conclude that the changes in extraction reflect a reduction in permeability of the blood-brain barrier. These results suggest that the behavioral responses to peripherally administered fragments of ACTH/MSH may depend, in part, on some action in the blood-brain barrier. These observations also suggest a mechanism by which such peptides may influence the behavioral effects of diffusion-limited drugs.
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats
D010446:Peptide Fragments; C013765:Org 2766; D000324:Adrenocorticotropic Hormone; D000983:Antipyrine