title: Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes.
abstract: BACKGROUND
  The melanocortin (MC) receptors have a key role in regulating body weight and pigmentation. They belong to the rhodopsin family of G protein-coupled receptors (GPCRs). The purpose of this study was to identify ancestral MC receptors in agnathan, river lamprey.
  
  
  RESULTS
  We report cloning of two MC receptors from river lamprey. The lamprey receptors, designated MCa and MCb, showed orthology to the MC1 and MC4 receptor subtypes, respectively. The molecular clock analysis suggested that lamprey MC receptor genes were not duplicated recently and diverged from each other more than 400 MYR ago. Expression and pharmacological characterization showed that the lamprey MCa receptor was able to bind and be activated by both lamprey and human MSH peptides. The lamprey MCa receptor had relatively high affinity for ACTH derived peptides similarly to the fish MC receptors. We found that both of the lamprey MC receptors were expressed in skin, while the MCb receptor was also found in liver, heart and skeletal muscle.
  
  
  CONCLUSIONS
  This study shows presence of MC receptors in agnathans indicating early signs of specific functions of melanocortin receptor subtypes.
authors.affiliation: Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Uppsala, Sweden. tatjana.haitina@neuro.uu.se <tatjana.haitina@neuro.uu.se>
authors.forename: Tatjana
authors.initials: T
authors.lastname: Haitina
authors.forename: Janis
authors.initials: J
authors.lastname: Klovins
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Maja
authors.initials: M
authors.lastname: Löwgren
authors.forename: Aneta
authors.initials: A
authors.lastname: Ringholm
authors.forename: Johan
authors.initials: J
authors.lastname: Enberg
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawauchi
authors.forename: Earl T
authors.initials: ET
authors.lastname: Larson
authors.forename: Robert
authors.initials: R
authors.lastname: Fredriksson
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002461:Cell Line, Transformed; D003366:Cosyntropin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D019143:Evolution, Molecular; D020440:Gene Duplication; D015723:Gene Library; D006196:Hagfishes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010446:Peptide Fragments / Q000378:metabolism; D010456:Peptides, Cyclic / Q000378:metabolism; D048428:Petromyzon / Q000235:genetics*; D010802:Phylogeny; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011485:Protein Binding; D025941:Protein Interaction Mapping; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D044101:Receptors, Melanocortin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015290:Second Messenger Systems; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism; D013045:Species Specificity; D014781:Viscera / Q000378:metabolism; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000378:metabolism; D019824:beta-MSH / Q000378:metabolism; D019825:gamma-MSH / Q000378:metabolism
chemical_list: C116098:HS 024; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D044102:Receptor, Melanocortin, Type 1; D044105:Receptor, Melanocortin, Type 4; D044101:Receptors, Melanocortin; D011993:Recombinant Fusion Proteins; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; D019824:beta-MSH; D019825:gamma-MSH; D003366:Cosyntropin; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; C028238:ACTH (1-17)