title: Characterisation of melanocortin receptor subtypes by radioligand binding analysis.
abstract: The DNAs encoding three melanocortin receptor subtypes (melanocortin MC1 receptor, melanocortin MC3 receptor and melanocortin MC5 receptor) were expressed individually in COS (CV-1 Origin, SV40) cells to characterise their ligand binding properties. The results indicated that [125I][Nle4, D-Phe7]alpha-MSH (melanocyte stimulating hormone) bound to a single saturable site with Kd values of 85.1 +/- 8.0 pmol/l (mean +/- S.E.M), 396 +/- 65 pmol/l and 5.05 +/- 1.00 nmol/l for melanocortin MC1 receptor, melanocortin MC3 receptor and melanocortin MC3 receptor, respectively. The melanocortin MC1 receptor and the melanocortin MC5 receptor showed a similar potency order to the melanocortic peptides examined which was markedly different from the potency order of the melanocortin MC3 receptor. The melanocortin MC1 receptor and melanocortin MC5 receptor had a relatively higher affinity for alpha-MSH than gamma-MSH and beta-MSH, whereas the melanocortin MC3 receptor had higher affinity for desacetyl-alpha-MSH, gamma-MSH and beta-MSH compared to alpha-MSH. The inclusion of the endopeptidase inhibitor phosphoramidon to prevent the breakdown of ACTH-(1-39) (adrenocorticotrophic hormone) to alpha-MSH, decreased ACTH-(1-39) binding affinity showing that ACTH-(1-39) had a much lower affinity for melanocortin MC1 receptor than reported earlier.
authors.affiliation: Department of Pharmaceutical Pharmacology, Biomedical Centre, Uppsala, Sweden.
authors.forename: H B
authors.initials: HB
authors.lastname: Schiöth
authors.forename: R
authors.initials: R
authors.lastname: Muceniece
authors.forename: J E
authors.initials: JE
authors.lastname: Wikberg
authors.forename: V
authors.initials: V
authors.lastname: Chhajlani
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000378:metabolism; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011869:Radioligand Assay; D018043:Receptors, Corticotropin / Q000145:classification* / Q000378:metabolism; D044101:Receptors, Melanocortin; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C013765:Org 2766; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones