University of Denver, Department of Biological Sciences, Denver, CO 80210, USA.
Eur J Pharmacol. 2012 Apr 5;680(1-3):1-7. doi: 10.1016/j.ejphar.2012.01.021. Epub 2012 Jan 31.
The melanocortin-5 receptor (MC(5)) of the dogfish Squalus acanthias (SacMC(5) receptor) can be functionally expressed in CHO cells in the absence of the co-expression of an exogenous MRAP cDNA. Both human ACTH(1-24) and dogfish ACTH(1-25) were much better stimulators of the SacMC(5) receptor than any of the mammalian or dogfish MSH ligands that were tested. The order of ligand selectivity for the dogfish melanocortins was ACTH(1-25)>αMSH>γ-MSH=δ-MSH>β-MSH. Unlike mammalian MC(5) receptors, the functional expression of the SacMC(5) receptor was not negatively impacted when the receptor was co-expressed with a cartilaginous fish (Callorhinchus milii) MRAP2 cDNA. However, co-expression with either mouse mMRAP1 or zebrafish zfMRAP1 increased the sensitivity of SacMC(5) receptor for hACTH(1-24) by at least one order of magnitude. Hence, SacMC(5) receptor has the potential to interact with MRAP1 orthologs and in this regard behaved more like a melanocortin MC(2) receptor ortholog than a melanocortin MC(5) receptor ortholog. These observations are discussed in light of the evolution of the melanocortin receptor gene family in cartilaginous fish, and the physiological implications of these observations are considered.
犬齿鲨黑素皮质素-5 受体（SacMC(5) 受体）可在 CHO 细胞中功能性表达，而无需共表达外源性 MRAP cDNA。人类 ACTH(1-24)和犬齿鲨 ACTH(1-25)均比所测试的任何哺乳动物或犬齿鲨 MSH 配体对 SacMC(5)受体的刺激作用要强得多。犬齿鲨黑素皮质素的配体选择性顺序为：ACTH(1-25)>αMSH>γ-MSH=δ-MSH>β-MSH。与哺乳动物 MC(5)受体不同，当 SacMC(5)受体与软骨鱼（Callorhinchus milii）MRAP2 cDNA 共表达时，其功能表达不受负面影响。然而，与鼠 mMRAP1 或斑马鱼 zfMRAP1 共表达会使 SacMC(5)受体对 hACTH(1-24)的敏感性增加至少一个数量级。因此，SacMC(5)受体有可能与 MRAP1 同源物相互作用，在这方面，它的行为更像是黑素皮质素 MC(2)受体的同源物，而不是黑素皮质素 MC(5)受体的同源物。这些观察结果是根据软骨鱼类黑素皮质素受体基因家族的进化情况进行讨论的，并考虑了这些观察结果的生理意义。
