Isolation and identification of melanin-concentrating hormone as the endogenous ligand of the SLC-1 receptor

Melanin-concentrating hormone (MCH), which is an orexigenic peptide, was is olated and identified as the endogenous ligand of the SLC-1 receptor. We es tablished a CHO cell line expressing the rat SLC-1 receptor to search for i ts endogenous ligand. The extract of rat whole brain showed inhibition of i ntracellular forskolin-induced cAMP accumulation in rat SLC-1-expressing CH O cells and was purified. Using HPLC purification, we isolated and identifi ed RICH as the endogenous ligand of the SLC-1 receptor. The authentic RICH demonstrated a dose-dependent inhibitory effect on cAMP accumulation in for skolin-stimulated rat and human SLC-l-expressing CHO cells with an EC50 val ue of 0.2 nM for both the rat and human SLC-1 receptors, This is the first description of the functional receptor for MCH. (C) 1999 Academic Press.