Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes.
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.
Haitina
Tatjana
T
Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Uppsala, Sweden. tatjana.haitina@neuro.uu.se <tatjana.haitina@neuro.uu.se>
Klovins
Janis
J
Takahashi
Akiyoshi
A
Löwgren
Maja
M
Ringholm
Aneta
A
Enberg
Johan
J
Kawauchi
Hiroshi
H
Larson
Earl T
ET
Fredriksson
Robert
R
Schiöth
Helgi B
HB
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
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)