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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\u2010hydroxytryptamine (5\u2010HT)\u20105\u2010HT1A\/1B receptor system, thereby resulting in skin hypopigmentation. Moreover, NK1R and 5\u2010HTR (except 5\u2010HT3) belong to GPCR. The present study aimed at assessing the possible existence of NK1R\u20105\u2010HTR interactions and related melanogenic functions. Western blot and PCR detection revealed that SP reduced expression of 5\u2010HT1A receptor\n                    <jats:italic>via<\/jats:italic>\n                    the NK1 receptor. Biochemical analyses showed that NK1R and 5\u2010HT1AR 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\u20105\u2010HT1AR decreased, and the depigmentation caused by SP and WAY100635 could be rescued. Importantly, pharmaceutical coadministration of NK1R agonist (SP) and 5\u2010HT1A antagonist (WAY100635) enhanced the NK1\u20135\u2010HT1A receptor coimmunoprecipitation along with the depigmentary response. SP and WAY100635 cooperation elicited activation of a signaling cascade (the extracellular, regulated protein kinase p\u2010JNK signaling pathway) and inhibition of p70S6K1 phosphorylation and greatly reduced melanin production\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    in mice and zebrafish. Moreover, the SP\u2010induced depigmentation response did not be occur in 5\u2010htr1aa\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    zebrafish embryos. Taken together, the results of our systemic study increases our knowledge of the roles of NK1R and 5\u2010HT1AR in mela\u2010nogenesis and provides possible, novel therapeutic strategies for treatment of skin hypo\/hyperpigmentation.\u2014Wu, H., Zhao, Y., Huang, Q., Cai, M., Pan, Q., Fu, M., An, X., Xia, Z., Liu, M., Jin, Y., He, L., Shang, J. NK1R\/5\u2010HT1AR interaction is related to the regulation of melanogenesis. FASEB J. 32, 3193\u20133214 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700564rr","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T17:21:05Z","timestamp":1518024065000},"page":"3193-3214","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["NK1R\/5\u2010HT1AR interaction is related to the regulation of melanogenesis"],"prefix":"10.1096","volume":"32","author":[{"given":"Huali","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"},{"name":"Department of Pharmacology China Pharmaceutical University  Nanjing 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