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 cent ral effect of ACTH 1-39 (ACTH) and peptides derived from the N-terminus (AC TH 1-10, Acetyl-ACTH 1-13-amide [alpha -MSH]) and C-terminus (ACTH 18-39 an d ACTH 22-39) of this peptide on feeding in 16 hour-fasted or rats fed ad l ibitum. 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 pr oduced a long-lasting increase in feeding in fasted, but not in fed rats. T he anorectic effects of N-terminal fragments of ACTH are recognised to be m ediated via melanocortin MC4 receptors. However, the orexigenic effects of the C-terminal fragments do not appear to be conducted via MC4 receptors, s ince neither ACTH 18-39 nor ACTH 22-39 stimulated cAMP accumulation nor inh ibited the ACTH-stimulated cAMP accumulation in HEK-293 cells transfected w ith the recombinant MC4 receptor.