Pharmacological characterization of melanocortin receptors in fish suggests an important role for ACTH

The melanocortin (MC) receptor subtypes have distinctive characteristic binding profiles. We found that the trout and Fugu MC4 receptors have similar affinity for α-MSH and β-MSH and a much higher affinity for ACTH than does the human MC4 receptor. The Fugu MC1 and the trout and Fugu MC5 receptors also have higher affinity for ACTH-derived peptides than α-, β-, or γ-MSH. It is tempting to speculate that ACTH-derived peptides may have played an important role as "original" ligands at the MC receptors, while the specificity of the different subtypes for the α-, β-, and γ-MSH peptides may have appeared at later stages during vertebrate evolution.