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Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes

Tatjana Haitina1, Janis Klovins12, Akiyoshi Takahashi3, Maja Löwgren1, Aneta Ringholm1, Johan Enberg1, Hiroshi Kawauchi3, Earl T Larson14, Robert Fredriksson1 and Helgi B Schiöth1*

  • * Corresponding author: Helgi B Schiöth

  • † Equal contributors

Author Affiliations

1 Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Uppsala SE 75124, Sweden

2 Biomedical Research and Study Centre, University of Latvia, Riga LV 1069, Latvia

3 School of Fisheries Sciences, Kitasato University, Sanriku, Ofunato, Iwate 022-0101, Japan

4 Department of Biology, Northeastern University, Boston, MA 02115, USA

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BMC Evolutionary Biology 2007, 7:101  doi:10.1186/1471-2148-7-101

Published: 29 June 2007



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.


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.


This study shows presence of MC receptors in agnathans indicating early signs of specific functions of melanocortin receptor subtypes.