Major pharmacological distinction of the ACTH receptor from other melanocortin receptors

• Published in: Life sciences (1973) 1996, Vol.59 (10), p.797-801
• Main Authors: Schiöth, Helgi B., Chhajlani, Vijay, Muceniece, Ruta, Klusa, Vija, Wikberg, Jarl E.S.
• Format: Article
• Language: English
• Subjects: 125I] [Nle 4; ACTH; Adrenal Cortex - metabolism; Adrenocorticotropic Hormone - metabolism; Animals; Cell Line; d-Phe 7]α-MSH ligand binding; Humans; Iodine Radioisotopes; melanocortin receptonsubtypes; Melanocyte-Stimulating Hormones - metabolism; Mice; Peptides - metabolism; Radioligand Assay; Receptors, Corticotropin - metabolism; Receptors, Melanocortin
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/0024-3205(96)00370-0

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 [ 125I]-labelled ACTH(1–39) with high affinity (K d ~ 130 pM). However, none of the melanocortin peptides NDP-MSH, α-MSH, β-MSH or γ1-MSH could compete with the binding of the labelled ACTH(1–39). When other MC receptor subtype DNAs (MC1, MC3 and MC4) were transfected into the Y1 cells, characteristic binding of the [ 125I]NDP-MSH appeared for each of the receptor subtype, but no specific binding was present in non-transfected cells. This is the first report clearly demonstrating that the ACTH receptor binds only ACTH, but not other melanocortin peptides.