title: Cross-talk between 5-hydroxytryptamine and substance P in the melanogensis and apoptosis of B16F10 melanoma cells.
abstract: Skin pigmentation is a complex process controlled by many different factors. Substance P (SP) regulates many biological functions, including melanogenesis and stress. Our previous study indicated that regulation of SP on melanocyte function was mediated by neurokinin 1 receptor (NK1 receptor). Substantial evidence has accumulated that psychological stress can be associated with skin pigmentation, so that the impact of 5-hydroxytryptamine (5-HT), one of the important factors participating in stress process, on melanogenesis has also been concerned. It has been reported that 5-HT induces melanin synthesis via 5-HT2A receptor. Furthermore, 5-HT2A receptor and NK1 receptor are G-protein coupled receptors (GPCRs) and both expressed on melanocyte, the present study was designed to investigate whether SP has influence on the adjustment function of 5-HT. Our data demonstrated that, SP inhibited 5-HT2A receptor expression to neutralize the pro-melanogenesis effect of 5-HT on B16F10 cells. The up-regulation of NK1 receptor expression was simultaneous with the down-regulation of 5-HT2A receptor treated by SP. This inhibition of 5-HT2A receptor expression by SP could be reversed by NK1 receptor antagonist Spantide I. Our studies indicated that SP could directly induce B16F10 cells apoptosis in vitro. 5-HT and 5-HT2A receptor agonist could mitigate this apoptotic effect of SP. It is the strong evidence of possible cross-talk between GPCRs and giving enlightenments when screening desirable drugs for target receptors.
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Patent Examination Cooperation Jiangsu Center of the Patent Office, SIPO, Suzhou, PR China.
authors.forename: Kun-kun
authors.initials: KK
authors.lastname: Geng
authors.affiliation: Department of Clinical Laboratory Science, Wuxi People's Hospital, Wuxi, PR China.
authors.forename: Feng-feng
authors.initials: FF
authors.lastname: Ping
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi, PR China.
authors.forename: Yue-ying
authors.initials: YY
authors.lastname: Gao
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Science, Jiangnan University, Wuxi, PR China. Electronic address: jnyxy2014@163.com.
authors.forename: Bai-nian
authors.initials: BN
authors.lastname: Feng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D013312:Stress, Physiological; D013373:Substance P / Q000494:pharmacology*
chemical_list: D008543:Melanins; D044402:Receptor, Serotonin, 5-HT2A; D018040:Receptors, Neurokinin-1; D012701:Serotonin; D013373:Substance P; D014442:Monophenol Monooxygenase
keywords: 5-HT; 5-HT(2A) receptor; Cross-talk; Melanogenesis; NK(1) receptor; SP