title: alpha-MSH and desacetyl-alpha-MSH signaling through melanocortin receptors.
abstract: The functional significance of N-terminal acetylation of ACTH[1-13]NH(2) is unknown. N-terminal acetylation of ACTH[1-13]NH(2) (known as desacetyl-alpha-MSH) to produce alpha-MSH enhances some activities of ACTH[1-13]NH(2) and virtually eliminates others. To determine whether alpha-MSH and desacetyl-alpha-MSH diverge in their coupling to melanocortin receptors in vitro, we measured the sensitivity of MC1, MC3, MC4, and MC5 receptors stably expressed in HEK293 cells to these peptides, functionally coupling them to adenylyl cyclase and a calcium signaling pathway. alpha-MSH and desacetyl-alpha-MSH similarly coupled these overexpressed receptors to both signaling pathways. In contrast, we discovered that alpha-MSH significantly increased primary rat osteoblast proliferation while for desacetyl-alpha-MSH there was only a trend to do the same. Osteoblast cells expressing very low levels of endogenous melanocortin receptors, in contrast with transfected HEK293 cells overexpressing a single melanocortin receptor, may provide an in vitro model for differentiating between alpha-MSH and desacetyl-alpha-MSH signaling.
authors.affiliation: Departments of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1, New Zealand. kmountjoy@auckland.ac.nz
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Mountjoy
authors.forename: Chia-Shan Jenny
authors.initials: CS
authors.lastname: Wu
authors.forename: Jillian
authors.initials: J
authors.lastname: Cornish
authors.forename: Karen E
authors.initials: KE
authors.lastname: Callon
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D054369:Agouti-Related Protein; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004435:Eating; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D010006:Osteoblasts / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D010858:Pigmentation / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D018043:Receptors, Corticotropin / Q000737:chemistry / Q000378:metabolism*; D044101:Receptors, Melanocortin; D015398:Signal Transduction / Q000502:physiology*; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D011506:Proteins; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D000262:Adenylyl Cyclases; D002118:Calcium