Searching for neurotransmitters as cognate ligands of orphan G protein-coupled receptor: finding receptor for melanin-concentrating hormone]

The melanin-concentrating hormone (MCH) is a cyclic peptide, identified originally from salmon pituitary as a regulator of pigmentary changes in background adaptation. The rat homologue was later also found to be expressed in the lateral hypothalamus and the zona incerta. Several lines of evidence indicate that MCH is a critical regulator of feeding and energy homeostasis. Its receptor remained unknown until we identified it as the orphan G protein-coupled receptor SLC-1, using a function-based assay with G protein chimera. A wide application of our strategy will permit the discovery of more natural transmitters.