Selectivity of [Phe-I7], [Ala6], and [D-Ala4,Gln5,Tyr6] substituted ACTH(4-10) analogues for the melanocortin receptors.
We tested [Ala6]ACTH(4-10) and [Phe-I7]ACTH(4-10)(putative MC receptor antagonists), [D-Ala4,Gln5,Tyr6]ACTH(4-10)(BIM 22015), and ACTH (4-10) with radioligand binding using transiently expressed human MC1, MC3, MC4, and MC3 receptors. [Phe-I7]ACTH(4-10) had higher affinity for the MC3, MC4, and MC3 receptors but lower for the MC1 compared to ACTH(4-10). [Ala6]ACTH(4-10) did not bind the MC1 receptor but had highest affinity for the MC4 receptor. The data indicate that the His6 has a specially important role in binding to the MC1 receptor. The BIM 22015 did not bind to these MC receptor subtypes, which indicates that the neurotrophic and myotrophic properties that are attributed to this peptide are mediated by some other receptor.
Schiöth
H B
HB
Department of Pharmaceutical Pharmacology, Uppsala University, Sweden.
Muceniece
R
R
Wikberg
J E
JE
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D003001:Cloning, Molecular; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011869:Radioligand Assay; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D044101:Receptors, Melanocortin; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D010446:Peptide Fragments; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D018000:Receptors, Peptide; C086971:melanocortin 5 receptor; D000324:Adrenocorticotropic Hormone; C011394:ACTH (4-10)