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

七鳃鳗中两种黑皮质素 (MC) 受体的功能表征显示其与 MC1 和 MC4 受体亚型具有同源性

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作者:Tatjana Haitina, Janis Klovins, Akiyoshi Takahashi, Maja Löwgren, Aneta Ringholm, Johan Enberg, Hiroshi Kawauchi, Earl T Larson, Robert Fredriksson, Helgi B Schiöth

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

Conclusion

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

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.

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