C-terminal fragments of ACTH stimulate feeding in fasted rats.
Peptides derived from pro-opiomelanocortin, including alpha-MSH and ACTH, play important roles in the regulation of feeding. We investigated the central effect of ACTH 1-39 (ACTH) and peptides derived from the N-terminus (ACTH 1-10, Acetyl-ACTH 1-13-amide [alpha-MSH]) and C-terminus (ACTH 18-39 and ACTH 22-39) of this peptide on feeding in 16 hour-fasted or rats fed ad libitum. As expected, ACTH reduced feeding in fed and previously fasted rats, although this anorectic effect was more pronounced in fasted rats. The N-terminal-derived peptide alpha-MSH, but not ACTH 1-10, reduced cumulative food intake over 2 h after its injection intracerebroventricularly (icv) in 16 h-fasted, but not in fed rats. In contrast, the C-terminal fragments produced a long-lasting increase in feeding in fasted, but not in fed rats. The anorectic effects of N-terminal fragments of ACTH are recognised to be mediated via melanocortin MC4 receptors. However, the orexigenic effects of the C-terminal fragments do not appear to be conducted via MC4 receptors, since neither ACTH 18-39 nor ACTH 22-39 stimulated cAMP accumulation nor inhibited the ACTH-stimulated cAMP accumulation in HEK-293 cells transfected with the recombinant MC4 receptor.
Al-Barazanji
K A
KA
Department of Vascular Biology, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK.
Miller
J E
JE
Rice
S Q
SQ
Arch
J R
JR
Chambers
J K
JK
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000819:agonists / Q000032:analysis; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005215:Fasting; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects
D010446:Peptide Fragments; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D011994:Recombinant Proteins; C011393:ACTH (1-10); D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP