'Dystonia'-like postural asymmetry after microinjection of ACTH N-terminal fragments but not after ACTH1-39 in rat brainstem suggests role of neuropeptide mutation in genetic movement disorder.
N-terminal fragments of adrenocorticotropin (ACTH) was reported to exert potent 'dystonia'-like effects on posture and locomotion following a unilateral microinjection into the rat brainstem. The high reliability of this phenomenon provided a suitable animal model for the study of these actions. The present structure-activity study showed that ACTH1-39, in contrast to its N-terminal fragments, did not have any 'dystonic' actions, however transient or slight. Thus, the folded conformation of [1-39] in vivo may prevent its N-terminal region from interacting with those CNS sites that trigger 'dystonic' actions. These results suggest that genetically-linked human dystonia may have originated in part as a consequence of a mutation in the processing of the ACTH molecule, resulting in an aberrantly-folded conformation that allows its N-terminal region to trigger the dystonic syndrome.
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects*; D004195:Disease Models, Animal; D004421:Dystonia / Q000139:chemically induced*; D008124:Locomotion; D008297:Male; D008845:Microinjections; D010446:Peptide Fragments / Q000494:pharmacology*; D011187:Posture; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D000324:Adrenocorticotropic Hormone