title: Characterization of the binding of MSH-B, HB-228, GHRP-6 and 153N-6 to the human melanocortin receptor subtypes.
abstract: We determined the binding affinities of the MSH analogues MSH-B, HP-228 and 153N-6 and of the enkephalin analogue GHRP-6 on a single eukaryotic cell line transiently expressing the human MC1, MC3, MC4 and MC5 receptors. Moreover, we tested the binding and cAMP response of MSH-B in comparison with alpha-MSH on murine B16 melanoma cells. Our results indicate that MSH-B has a potency similar to that of alpha-MSH and that these two peptides induce similar cAMP responses in murine B16 melanoma cells. HP-228 has its highest affinity for the MC1 receptor. For the other receptors, it has slightly higher affinity for the MC5 receptor than for the MC3 and MC4 receptors. 153N-6 was found to be selective for the MC1 receptor. GHRP-6 was found to bind to the MC1 and the MC5 receptors despite its low structural homology with alpha-MSH. [D-Lys3]GHRP-6 bound to all the four MC receptors with similar affinities. The structurally related Met-enkephalin and the functionally related GHRH, as well as LHRH and somatostatin-14 did not bind to these MC receptors. The low affinity of the GH-releasing/enkephalin peptides may indicate that they do not interact with the MC receptors at pharmacologically relevant concentrations.
authors.affiliation: Department of Pharmaceutical Pharmacology, Uppsala University, Sweden. helgis@bmc.uu.se
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
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D019556:COS Cells / Q000502:physiology; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression; D006728:Hormones / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism* / Q000494:pharmacology; D008545:Melanoma; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology; D018043:Receptors, Corticotropin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D044101:Receptors, Melanocortin; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D000521:alpha-MSH / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: C101068:153N-6 peptide; D006728:Hormones; D009842:Oligopeptides; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C096756:HP 228; C041048:growth hormone releasing hexapeptide; D000521:alpha-MSH; D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP