七鳃鳗中两种与MC1和MC4受体亚型具有直系同源性的黑皮质素（MC）受体的功能特性

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

作者信息

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

机构信息

Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Uppsala, Sweden.

出版信息

BMC Evol Biol. 2007 Jun 29;7:101. doi: 10.1186/1471-2148-7-101.

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.

CONCLUSION

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

背景

黑皮质素（MC）受体在调节体重和色素沉着方面发挥着关键作用。它们属于G蛋白偶联受体（GPCRs）的视紫红质家族。本研究的目的是鉴定无颌类动物河鳗中的原始MC受体。

结果

我们报道了从河鳗中克隆出两种MC受体。鳗鲡受体分别命名为MCa和MCb，它们分别与MC1和MC4受体亚型具有直系同源关系。分子钟分析表明，鳗鲡MC受体基因并非近期复制，且在4亿多年前就已彼此分化。表达和药理学特性表明，鳗鲡MCa受体能够结合鳗鲡和人类的促黑素（MSH）肽并被其激活。与鱼类MC受体类似，鳗鲡MCa受体对促肾上腺皮质激素（ACTH）衍生肽具有较高的亲和力。我们发现，鳗鲡的两种MC受体均在皮肤中表达，而MCb受体在肝脏、心脏和骨骼肌中也有发现。