Comparative analysis of melanin-concentrating hormone structure and activity in fishes and mammals

A comparative analysis of the structure of the melanin-concentrating hormone (MCH) precursor reveals that this sequence has been subjected to a higher selection pressure in mammals than in teleosts, suggesting that the structural constraints have not been the same throughout the vertebrate lineage. In contrast, the MCH peptide sequence has been very well conserved in all species. A sensitive and reproducible eel skin assay was developed and allowed us to define the structural features needed for a full MCH bioactivity. It was shown that the minimal structure carrying the critical residues was the same in fishes and in mammals. A pharmacological approach confirmed that MCH receptor activation decreased the cAMP levels in the fish skin, but this effect appeared to be independent from a Galphai protein. We propose that one of the intracellular signaling pathways of the MCH receptor in fish skin is the activation of one or several cellular phosphodiesterases.