Role of Amine Neurotransmitters and Their Receptors in Skin Pigmentation: Therapeutic Implication

Abstract

Skin pigmentation can occur due to increased melanin, including melanocyte proliferation, melanin biosynthesis, or melanocyte migration. There are many factors that influence the melanin production process, but the role of neurotransmitters in this process is still unclear. We found that histamine and serotonin influence the different stages of melanogenesis and melanogenesis, which increase melanogenesis. Since then, several related papers have been published, and from these papers, it has been recognised that the role of neurotransmitters in skin-pigment-related diseases needs to be summarised. By introducing the role of neurotransmitters in the regulation of various pigment disorders, including vitiligo and melasma, through this review, many researchers can be expected to try to apply neurotransmitter-related agonists and antagonists as treatments for skin pigment disorders.

Deregulation of Trace Amine-Associated Receptors (TAAR) Expression and Signaling Mode in Melanoma

“…Skin also is intensively innervated by noradrenergic and cholinergic nerves. Catecholamines seem to participate in intercellular interaction in skin and regulation of melanin production and, possibly, melanocyte survival [ 28 ]. The presence of TAs which are closely related to catecholamines in melanocytes and the inclusion of these compounds is biological processes in the skin remain uncharacterized.…”

“…Inhibition of DRD2 expression suppresses proliferation in breast cancer cell lines but promotes proliferation in non-small cell lung cancer cells [ 25 ]. DRD1 and DRD2 are expressed in melanoma samples and nondamaged human skin [ 26 , 27 , 28 , 29 ]. Dopamine leads to a marked cell proliferation decrease in melanoma cells [ 30 ].…”

“…Dopamine leads to a marked cell proliferation decrease in melanoma cells [ 30 ]. It also is cytotoxic against noncancerous melanocytes [ 28 , 31 ]. DRD4 receptor antagonists reduced the melanin contents, MITF expression, and, consequently, ERK activation in melanoma cells [ 32 ].…”

Loss of EMP2 Inhibits Melanogenesis of MNT1 Melanoma Cells via Regulation of TRP-2

“…Skin pigmentation depends on the cooperation of melanocytes and keratinocytes (KC), and the delivery and distribution of melanosomes to KC is an important process in skin pigmentation ( Lee, 2015 ; Serre et al ., 2018 ). Skin pigmentation disorders can be widespread, and the resulting pigmentation changes are classified as depigmentation, hypopigmentation, and hyperpigmentation ( Enkhtaivan and Lee, 2021 ). Skin hyperpigmentation is an especially common skin condition and includes melasma, melanoma, and post-inflammatory hyperpigmentation ( Lambert et al ., 2019 ).…”

“…TYR is involved in melanin biosynthesis as a rate-limiting enzyme, catalyzing the hydroxylation of L-tyrosine to L-3, 4-dihydroxyphenylalanine (DOPA) and the oxidation of DOPA to dopaquinone is catalyzed by TYR. Once dopaquinone is oxidized to dopachrome, TRP-2 catalyzes dopachrome to 5,6-dihydroxyindole-2-carboxylic acid ( Yokoyama et al ., 1994 ; Lee et al ., 2011 ; Enkhtaivan and Lee, 2021 ). In addition, TRP-1 is involved in melanogenesis by regulating the activity of TYR ( Kobayashi et al ., 1994 ).…”