SLC-1 receptor mediates effect of melanin-concentrating hormone on feedingbehavior in rat: A structure-activity study

Several studies have shown that melanin-concentrating hormone (MCH) is an o rexigenic peptide in rat. In the present study, a structure-activity relati onship with MCH analogs was performed in rat, both in vitro and in vivo. On rat recombinant SLC-1 receptor, both CAMP inhibition and [I-125]S36057 bin ding were measured. In vivo, these analogs were injected intracerebroventri cularly in rats and their effects were evaluated upon food intake. First, d ata obtained with the rat recombinant receptor were highly correlated with those obtained from its human counterpart. Second, agonist potencies in the CAMP assay were also highly correlated with binding affinities. These pept ides could be classified into several groups according to their potency at the SLC-1 receptor (from subnanomolar activity to complete inactivity). Ind eed, there was a strong correlation between their effects upon food intake and the results obtained at the rat SLC-1 receptor. The present report desc ribes for the first time the rat SLC-1 receptor pharmacology and clearly es tablishes the relevance of the SLC-1 receptor in feeding behavior.