A Novel Role of Serotonin Receptor 2B Agonist as an Anti-Melanogenesis Agent

Abstract

BW723C86, a serotonin receptor 2B agonist, has been investigated as a potential therapeutic for various conditions such as anxiety, hyperphagia and hypertension. However, the functional role of BW723C86 against melanogenesis remains unclear. In this study, we investigate the effect of serotonin receptor 2B (5-HTR2B) agonist on melanogenesis and elucidate the mechanism involved. BW723C86 reduced melanin synthesis and intracellular tyrosinase activity in melan-A cells and normal human melanocytes. The expression of melanogenesis-related proteins (tyrosinase, TRP-1 and TRP-2) and microphthalmia-associated transcription factor (MITF) in melan-A cells decreased after BW723C86 treatment. The promoter activity of MITF was also reduced by BW723C86 treatment. The reduced level of MITF was associated with inhibition of protein kinase A (PKA) and cAMP response element-binding protein (CREB) activation by BW723C86 treatment. These results suggest that the serotonin agonist BW723C86 could be a potential therapeutic agent for skin hyperpigmentation disorders.

Characterization of serotonin and N‐acetylserotonin systems in the human epidermis and skin cells

“…Serotonin's role in the regulation of pigmentary responses is complex and dependent on ligand activation of a particular receptor . In melanophores, pigment granule dispersion or aggregation is dependent on activation on 5HT3 or 5HT1/2, respectively .…”

“…In human melanomas, serotonin or serotonin uptake inhibitors were reported to inhibit melanogenesis . However, 5HT1A/2A or 5HT2B can stimulate or inhibit melanogenesis, respectively . Therefore, we tested the phenotypic effects of serotonin and NAS on melanogenic activity using the pigmented melanoma line MNT‐1 (Figure ).…”

“…Human skin or skin cells express genes and proteins of 5HTR1A, 1B, 2A, 2B, 2C, 3, and 7 receptors, whose activation would contribute to the pleiotropic effects of serotonin on skin functions including vascular and inflammatory responses, wound healing and potentially contributing to regulation of hair cycling and melanin pigmentation . However, there is a paucity of information on the biological role of NAS except its contribution to photoprotection against UVB .…”

Interaction of hepatic stellate cells with neutrophils and macrophages in the liver following oncogenic kras activation in transgenic zebrafish

“…SB204741 has been previously used as an antagonist of Htr2b 35 , 37 and it has been shown to have 135 times higher selectivity over the most relevant serotonin receptors, Htr2c 38 . BW723C86 has also been widely used for investigating the effects of activation of Htr2b in disease progression 39 – 41 . Gross morphology was captured after the treatment and all the larvae were shown in the left lateral view (Fig.…”

Novel Anti-Melanogenesis Properties of Polydeoxyribonucleotide, a Popular Wound Healing Booster

“…Melanogenesis is regulated mainly by the activity and expression of the rate-limiting enzyme tyrosinase, a copper-containing glycoprotein. TRP-1 and TRP-2 are two other major melanogenic enzymes, whereas MITF is a major transcription factor involved in the regulation of the abovementioned melanocyte-specific enzymes [ 10 , 25 , 26 ]. In this study, PDRN treatment led to decreases in protein levels of tyrosinase, TRP-1, and MITF.…”