Melatonin receptor

melatonin receptor 1A
Identifiers
Symbol	MTNR1A
Entrez	4543
HUGO	7463
OMIM	600665
RefSeq	NM_005958
UniProt	P48039
Other data
Locus	Chr. 4 q35.1

melatonin receptor 1B
Identifiers
Symbol	MTNR1B
Entrez	4544
HUGO	7464
OMIM	600804
RefSeq	NM_005959
UniProt	P49286
Other data
Locus	Chr. 11 q21-q22

A melatonin receptor is a G protein-coupled receptor (GPCR) which binds melatonin.^[1]

Three types of melatonin receptor have been cloned. The MT₁ (or Mel_1A or MTNR1A) and MT₂ (or Mel_1B or MTNR1B) receptor subtypes are present in humans and other mammals,^[2] while an additional melatonin receptor subtype MT₃ (or Mel_1C or MTNR1C) has been identified in amphibia and birds.^[3]

Expression patterns

In mammals, melatonin receptors are found in the brain and some peripheral organs. However, there is considerable variation in the density and location of MT receptor expression between species.^[4]

MT₁

In humans, The MT₁ subtype is expressed in the pars tuberalis of the pituitary gland and the suprachiasmatic nuclei of the hypothalamus.

MT₂

The MT₂ subtype is expressed in the retina. MT₂ receptor mRNA has not been detected by in situ hybridization in the rat suprachiasmatic nucleus or pars tuberalis.^[5]

MT₃

The MT₃ subtype of many non-mammalian vertebrates is expressed in various brain areas.^[3]

MT Receptor function

MT₁

In humans, The MT₁ subtype's expression in the pars tuberalis of the pituitary gland and suprachiasmatic nuclei of the hypothalamus is indicative of melatonin's circadian and reproductive functional involvement.

MT₂

In humans, the MT₂ subtype's expression in the retina is suggestive of melatonin's effect on the mammalian retina occurring through this receptor. Research suggests that melatonin acts to inhibit the Ca2+-dependent release of dopamine.^[5] Melatonin's action in the retina is believed to affect several light-dependent functions, including phagocytosis and photopigment disc shedding.^[6]

Selective Ligands

Agonists

Antagonists

References

↑ Reppert SM (1997). "Melatonin receptors: molecular biology of a new family of G protein-coupled receptors". J. Biol. Rhythms. 12 (6): 528–31. doi:10.1177/074873049701200606. PMID 9406026.
↑ Reppert SM, Weaver DR, Godson C (1996). "Melatonin receptors step into the light: cloning and classification of subtypes". Trends Pharmacol. Sci. 17 (3): 100–02. doi:10.1016/0165-6147(96)10005-5. PMID 8936344.
1 2 Sugden D, Davidson K, Hough KA, Teh MT (2004). "Melatonin, melatonin receptors and melanophores: a moving story". Pigment Cell Res. 17 (5): 454–60. doi:10.1111/j.1600-0749.2004.00185.x. PMID 15357831.
↑ Morgan PJ, Barrett P, Howell HE, Helliwell R (1994). "Melatonin receptors: localization, molecular pharmacology and physiological significance". Neurochem. Int. 24 (2): 101–46. doi:10.1016/0197-0186(94)90100-7. PMID 8161940.
1 2 Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (September 1995). "Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor". Proc. Natl. Acad. Sci. U.S.A. 92 (19): 8734–38. Bibcode:1995PNAS...92.8734R. doi:10.1073/pnas.92.19.8734. PMC 41041. PMID 7568007.
↑ Besharse JC, Dunis DA (March 1983). "Methoxyindoles and photoreceptor metabolism: activation of rod shedding". Science. 219 (4590): 1341–43. Bibcode:1983Sci...219.1341B. doi:10.1126/science.6828862. PMID 6828862.
↑ Nickelsen T, Samel A, Vejvoda M, Wenzel J, Smith B, Gerzer R (September 2002). "Chronobiotic effects of the melatonin agonist LY 156735 following a simulated 9h time shift: results of a placebo-controlled trial". Chronobiol. Int. 19 (5): 915–36. doi:10.1081/cbi-120014108. PMID 12405554.

External links

"Melatonin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
Melatonin Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Adhesion	ADGRG (1 2 3 4 5 6 7)

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60 Vomeronasal receptor)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

Melatonin receptor modulators

MTR	Agonists: 2-Iodomelatonin 2-Phenylmelatonin 5-Methoxyluzindole 6-Chloromelatonin 6-Fluoromelatonin 6-Hydroxymelatonin 6-Methoxymelatonin 6,7-Dichloro-2-methylmelatonin 8-M-PDOT Agomelatine AMMTC GR-135,531 (of MT₃) GR-196,429 Melatonin N-Acetylserotonin (normelatonin) N-Acetyltryptamine N-Butanoylmelatonin N-Propionylmelatonin Piromelatine Ramelteon S-24268 S-25150 Tasimelteon TIK-301 (LY-156,735) Antagonists: 4-P-ADOT 4-P-PDOT Afobazole DH-97 Luzindole N-Acetyltryptamine (of MT₃) Prazosin (of MT₃) S-20928 S-22153 S-24601 S-25567 S-26131

See also: Adrenergics Dopaminergics Serotonergics Monoamine reuptake and release modulators Monoamine metabolism modulators Monoamine neurotoxins

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