NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis
Wu, Huali ; Zhao, Yucheng ; Huang, Qiaoling ; Cai, Minxuan ; Pan, Qi ; Fu, Mengsi ; An, Xiaohong ; Xia, Zhenjiang ; Liu, Meng ; Jin, Yu ; He, Ling ; Shang, Jing
Source PublicationFASEB JOURNAL
AbstractSubstance P (SP) is a candidate mediator along the brain-skin axis and can mimic the effects of stress to regulate melanogenesis. Previously, we and others have found that the regulation of SP for pigmentary function was mediated by neurokinin 1 receptor (NK1R). Emerging evidence has accumulated that psychologic stress can induce dysfunction in the cutaneous serotonin 5-hydroxytryptamine (5-HT)-5-HT1A/1B receptor system, thereby resulting in skin hypopigmentation. Moreover, NK1R and 5-HTR (except 5-HT3) belong to GPCR. The present study aimed at assessing the possible existence of NK1R-5-HTR interactions and related melanogenic functions. Western blot and PCR detection revealed that SP reduced expression of 5-HT1A receptor via the NK1 receptor. Biochemical analyses showed that NK1R and 5-HT1AR could colocalize and interact in a cell and in the skin. When the N terminus of the NK1R protein was removed NK1R surface targeting was prevented, the interaction between NK1R-5-HT1AR decreased, and the depigmentation caused by SP and WAY100635 could be rescued. Importantly, pharmaceutical coadministration of NK1R agonist (SP) and 5-HT1A antagonist (WAY100635) enhanced the NK1-5-HT1A receptor coimmunoprecipitation along with the depigmentary response. SP and WAY100635 cooperation elicited activation of a signaling cascade (the extracellular, regulated protein kinase p-JNK signaling pathway) and inhibition of p70S6K1 phosphorylation and greatly reduced melanin production in vitro and in vivo in mice and zebrafish. Moreover, the SP-induced depigmentation response did not be occur in 5-htr1aa(+/-)zebrafish embryos. Taken together, the results of our systemic study increases our knowledge of the roles of NK1R and 5-HT1AR in melanogenesis and provides possible, novel therapeutic strategies for treatment of skin hypo/hyperpigmentation.
Document Type期刊论文
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GB/T 7714
Wu, Huali,Zhao, Yucheng,Huang, Qiaoling,et al. NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis[J]. FASEB JOURNAL,2018.
APA Wu, Huali.,Zhao, Yucheng.,Huang, Qiaoling.,Cai, Minxuan.,Pan, Qi.,...&Shang, Jing.(2018).NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis.FASEB JOURNAL.
MLA Wu, Huali,et al."NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis".FASEB JOURNAL (2018).
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