ACTH-(1-24) and alpha-MSH antagonize dopamine receptor-mediated inhibition of striatal dopamine and acetylcholine release.
The effects of ACTH-(1-24), alpha-MSH and ACTH-(4-10) were studied on the electrically evoked release of 3H-dopamine and 14C-acetylcholine from striatal slices in the absence and presence of the dopamine receptor agonist TL-99. None of the peptides affected transmitter release when TL-99 was not present. ACTH-(1-24) and alpha-MSH concentration-dependently antagonized the inhibition of striatal transmitter release induced by dopamine receptor stimulation due to the presence of TL-99. ACTH-(1-24), 10(-7)M, reduced the TL-99-induced inhibition of the release of both dopamine and acetylcholine by approximately 50%, and 5 X 10(-6) M ACTH-(1-24) restored the release fully to control values. alpha-MSH was less effective by a factor 20-30 in counteracting the release-inhibiting effect of TL-99. ACTH-(4-10) had no effect at any of the concentrations tested. These results show that ACTH/MSH-like neuropeptides may act by modulating dopamine receptor functions in rat striatum.
D000109:Acetylcholine / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003366:Cosyntropin / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D003366:Cosyntropin; C016893:2-(N,N-dimethylamino)-6,7-dihydroxytetralin; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D000109:Acetylcholine; D004298:Dopamine