Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer of the skin's epidermis, the middle layer of the eye, the inner ear, vaginal epithelium, meninges, bones, and heart. Melanin is a dark pigment primarily responsible for skin color. Once synthesized, melanin is contained in special organelles called melanosomes which can be transported to nearby keratinocytes to induce pigmentation. Thus darker skin tones have more melanosomes present than lighter skin tones. Functionally, melanin serves as protection against UV radiation. Melanocytes also have a role in the immune system.
5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.
Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper Mason pathway. Firstly, the hydroxylation of a monophenol and secondly, the conversion of an o-diphenol to the corresponding o-quinone. o-Quinone undergoes several reactions to eventually form melanin. Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation. It is found inside melanosomes which are synthesized in the skin melanocytes. In humans, the tyrosinase enzyme is encoded by the TYR gene.
Skin whitening, also known as skin lightening and skin bleaching, is the practice of using chemical substances in an attempt to lighten the skin or provide an even skin color by reducing the melanin concentration in the skin. Several chemicals have been shown to be effective in skin whitening, while some have proven to be toxic or have questionable safety profiles. This includes mercury compounds which may cause neurological problems and kidney problems.
The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations. 5-HT is short for 5-hydroxy-tryptamine or serotonin. This is the main excitatory receptor subtype among the GPCRs for serotonin, although 5-HT2A may also have an inhibitory effect on certain areas such as the visual cortex and the orbitofrontal cortex. This receptor was first noted for its importance as a target of serotonergic psychedelic drugs such as LSD and psilocybin mushrooms. Later it came back to prominence because it was also found to be mediating, at least partly, the action of many antipsychotic drugs, especially the atypical ones.
Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the MITF gene.
5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the HTR1B gene. The 5-HT1B receptor is a 5-HT receptor subtype.
5-hydroxytryptamine (serotonin) receptor 1F, also known as HTR1F is a 5-HT1 receptor protein and also denotes the human gene encoding it.
5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT).
Tyrosinase-related protein 1, also known as TYRP1, is an intermembrane enzyme which in humans is encoded by the TYRP1 gene.
(+)-BW373U86 is an opioid analgesic drug used in scientific research.
5-Carboxamidotryptamine (5-CT) is a tryptamine derivative closely related to the neurotransmitter serotonin.
Ocular albinism type 1(OA1) is the most common type of ocular albinism, with a prevalence rate of 1:50,000. It is an inheritable classical Mendelian type X-linked recessive disorder wherein the retinal pigment epithelium lacks pigment while hair and skin appear normal. Since it is usually an X-linked disorder, it occurs mostly in males, while females are carriers unless they are homozygous. About 60 missense and nonsense mutations, insertions, and deletions have been identified in Oa1. Mutations in OA1 have been linked to defective glycosylation and thus improper intracellular transportation.
SB-216641 is a drug which is a selective antagonist for the serotonin receptor 5-HT1B, with around 25x selectivity over the closely related 5-HT1D receptor. It is used in scientific research, and has demonstrated anxiolytic effects in animal studies.
5-Benzyloxytryptamine (5-BT), is a tryptamine derivative which acts as an agonist at the 5-HT1D, 5-HT2 and 5-HT6 serotonin receptors, and an antagonist of TRPM8.
The melanocortin 1 receptor (MC1R), also known as melanocyte-stimulating hormone receptor (MSHR), melanin-activating peptide receptor, or melanotropin receptor, is a G protein–coupled receptor that binds to a class of pituitary peptide hormones known as the melanocortins, which include adrenocorticotropic hormone (ACTH) and the different forms of melanocyte-stimulating hormone (MSH). It is coupled to Gαs and upregulates levels of cAMP by activating adenylyl cyclase in cells expressing this receptor. It is normally expressed in skin and melanocytes, and to a lesser degree in periaqueductal gray matter, astrocytes and leukocytes. In skin cancer, MC1R is highly expressed in melanomas but not carcinomas.
SB-206553 is a drug which acts as a mixed antagonist for the 5-HT2B and 5-HT2C serotonin receptors. It has anxiolytic properties in animal studies and interacts with a range of other drugs. It has also been shown to act as a positive allosteric modulator of α7 nicotinic acetylcholine receptors. Modified derivatives of SB-206553 have been used to probe the structure of the 5-HT2B receptor.
α-Melanocyte-stimulating hormone (α-MSH) is an endogenous peptide hormone and neuropeptide of the melanocortin family, with a tridecapeptide structure and the amino acid sequence Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. It is the most important of the melanocyte-stimulating hormones (MSHs) (also known as melanotropins) in stimulating melanogenesis, a process that in mammals (including humans) is responsible for pigmentation primarily of the hair and skin. It also plays a role in feeding behavior, energy homeostasis, sexual activity, and protection against ischemia and reperfusion injury.
25CN-NBOH is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 at the University of Copenhagen. This compound is notable as one of the most selective agonist ligands for the 5-HT2A receptor yet discovered, with a pKi of 8.88 at the human 5-HT2A receptor and with 100x selectivity for 5-HT2A over 5-HT2C, and 46x selectivity for 5-HT2A over 5-HT2B. A tritiated version of 25CN-NBOH has also been accessed and used for more detailed investigations of the binding to 5-HT2 receptors and autoradiography.
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