THE MELANOCORTIN-1, MELANOCORTIN-3, MELANOCORTIN-4 OR MELANOCORTIN-5 RECEPTORS DO NOT HAVE A BINDING EPITOPE FOR ACTH BEYOND THE SEQUENCE OF ALPHA-MSH

ACTH(1-39), and several shorter N- and/or C-terminally truncated fragm ents of ACTH, with and without N-terminal acetylation and/or C-termina l amidation, were tested for binding on a single eukaryotic cell line transiently and independently expressing the melanocortin MC1, MC3, MC 4 and MC5 receptors. The results show that none of these MC receptors has specific binding epitopes for the ACTH peptides beyond the amino a cid sequence of a-MSH, when tested for their ability to compete with I -125-labelled [Nle(4),D-Phe(7)]alpha-MSH and ACTH. The MC3 receptor fa vours the natural desacetylated N-terminal end of the ACTH peptides, a nd it has generally more than 10-fold higher affinity for the ACTH pep tides than the MC4 receptor. Considering earlier anatomical localisati on data, together with the present data, we suggest that the MC3 recep tor is the most likely candidate of the MC receptors to mediate the sh ort-loop negative feedback release of corticotrophin-releasing factor (CRF) caused by ACTH/MSH peptides.