The mouse adrenocortical cell line Y1, that expresses ACTH receptors (
MC2R), was used to probe the binding of ACTH and MSH peptides by using
radio-labelled ACTH (1-39). The Y1 cells were found to bind [I-125]-l
abelled ACTH(1-39) with high affinity (K-d similar to 130 pM). However
, none of the melanocortin peptides NDP-MSH, alpha-MSH, beta-MSH or ga
mma 1-MSH could compete with the binding of the labelled ACTH(1-39). W
hen other MC receptor subtype DNAs (MC1, MC3 and MC4) were transfected
into the Y1 cells, characteristic binding of the [I-125]NDP-MSH appea
red for each of the receptor subtype, but no specific binding was pres
ent in non-transfected cells. This is the first report clearly demonst
rating that the ACTH receptor binds only ACTH, but not other melanocor
tin peptides.