NK1R/5‐HT1AR interaction is related to the regulation of melanogenesis

Abstract

Substance 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.-Wu, 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-HT1AR interaction is related to the regulation of melanogenesis.

Specificity of aminergic status in skin and tumor of C57BL/6-PlautmI.IBug-This Plau6FDhu/GFDhu mice with B16/F10 melanoma

“…Иммунная и сосудистая системы кожи являются традиционными мишенями для серотонина в биорегуляторных процессах. Считается, что он опосредует меланогенез-модулирующие эффекты стресса, рецепторы 5-HT1A/1B особенно важны в связи между мозгом и кожей [10].…”

Reversing Gray Hair: Inspiring the Development of New Therapies Through Research on Hair Pigmentation and Repigmentation Progress

“…Studies have shown that in B10F16 melanoma cells, SP not only exerts a synergistic effect with CGRP, but also induces apoptosis in B10F16 cells and downregulates 5-hydroxytryptamine (5-HT)1A receptor and 5-HT2A receptor, both of which promote melanogenesis. This effect is mediated by binding to the NK1R receptor and activating S6 kinase 1 (S6K1) while inhibiting the MAPK signaling pathway 87 - 89 . Moreover, excess SP induced by mental stress decreases melanogenesis through keratinocytes.…”

HTR1D functions as a key target of HOXA10-AS/miR-340-3p axis to promote the malignant outcome of pancreatic cancer via PI3K-AKT signaling pathway

“…In addition, 5-HT Ivyspring International Publisher receptors (5-HTRs) serve vital roles in these processes by binding to the surface of cell membrane [11]. According to recent studies, 5-HTRs were linked to malignant tumors, such as melanoma [12], breast cancer [13,14], lung cancer [15] and colon cancer [16]. For example, 5-HTR1B, 5-HTR3 and 5-HTR4 were proven to promote the proliferation of colorectal cancer cells (CRCs) [17].…”