Melatonin receptors: Introduction

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General

The hormone melatonin is mainly produced by the pineal gland following a circadian rhythm, with high levels during the subjective night. In some cases melatonin can also be produced by extra-pineal sites like in cells from the innate immune system in a non-circadian manner. Melatonin regulates a variety of physiological and neuroendocrine functions through activation of G protein-coupled melatonin receptors in target tissues [15,32,39,64,67].

The use of the radioligands [3H]melatonin and 2-[125I]iodomelatonin has led to the localization and characterization in native tissues of a number of putative melatonin binding sites with well-defined and distinct pharmacological profiles [15]. The first classification of putative melatonin receptors into ML1 and ML2 types was based on kinetic and pharmacological differences of 2-[125I]iodomelatonin binding [13]. The pharmacological profile (2-iodomelatonin > melatonin >> N-acetylserotonin) of 2-[125I]iodomelatonin binding to mammalian retina and pars tuberalis corresponds closely to that of the functional melatonin receptor characterized in rabbit retina [13-14,31,36,42,51]. By contrast the pharmacology (2-iodomelatonin > melatonin = N-acetylserotonin) of 2-[125I]iodomelatonin binding to hamster brain membranes was distinguished by N-acetylserotonin, which showed equal affinity with melatonin [13-14,31,36] and corresponds to the ML2 type.

Cloning studies have revealed two recombinant mammalian melatonin receptors - Mel1a and Mel1b, now termed MT1 and MT2 [48-51] both encoding 2-[125I]iodomelatonin binding sites showing the general pharmacology of the ML1 type [18,51]. These two definitive melatonin receptors were defined as unique entities on the basis of their molecular structure and chromosomal localization [6,48-51,58]. The human melatonin receptors, (h MT1 and h MT2) show 60% homology to each other at the amino acid (aa) level. They have distinct pharmacological profiles of partial agonist and antagonist binding affinities for 2-[125I]iodomelatonin and [3H]melatonin [7,14-15,18,25]. The ML2 2-[125I]iodomelatonin binding site (now termed MT3), was identified in washed hamster brain membranes and originally thought to be a GPCR [20-22,29,41]. A new site with the pharmacological characteristics of the MT3 2-[125I]-iodomelatonin binding site in cytoplasmic fractions was been identified with quinone reductase 2 [46]. Indeed, brain and kidney membranes from mice with genetic deletion of quinone reductase 2 lacked specific 2-[125I]iodomelatonin binding to MT3 binding sites [38]. Whether the MT3 binding sites in washed brain membranes and on quinone reductase are the same or different binding sites is still an open question. The MT3 site is no longer considered within IUPHAR classification of G protein-coupled melatonin receptors.

MT1 receptors

A number of non-selective melatonin receptor agonists and antagonists have been identified [9-10,15,24-29,52,60,66-67], which have been useful in the pharmacological characterization of melatonin receptors in native tissues [18]. Work carried out with recombinant h MT1 receptors led to the identification of various analogues as inverse agonists (e.g., luzindole, 4P-PDOT) on recombinant human receptors [7,19] and in native tissues [7,17,23,59].

MT1 receptors signal via inhibitory G proteins (Gαi and Gαo) leading to adenylate cyclase inhibition and possibly inositol phosphate stimulation in recombinant systems. However, characterization of MT1 melatonin receptors mediating signalling in native tissues have not been reported [14,30-31,36,42,53]. In certain native tissues (e.g. sheep pars tuberalis, rat cerebral and caudal arteries) melatonin responses are presumably mediated through activation of MT1 receptors. However, most of the evidence for the presence of this receptor is indirect (i.e. expression of specific mRNA; immunohistochemistry) [1,48-50,54-57], with the rat caudal artery being the only tissue where pharmacological characterization of this receptor has been reported [8,35,40,61-63]. Using mice with genetic deletion of the MT1 melatonin receptor the following functions for this receptor have been demonstrated a) Inhibition neuronal firing (suprachiasmatic nucleus, [37]), b) phase shift of onset of circadian rhythm of running wheel activity (MT1 KO mouse, [16]); c) regulation of photoperiodic information (pars tuberalis, [65]).

MT2 receptors

Recently, a number of MT2 receptor-selective melatonin receptor agonists, partial agonists and antagonists have been identified [2,9,15,18,34,43,45,52,67]. In rabbit retina melatonin inhibits [3H]dopamine release through activation of an MT2 presynaptic heteroreceptor showing a pharmacological profile of partial agonists and antagonists (KB values) similar to that of the recombinant human MT2 receptor (Ki for inhibition of 2-[125I]iodomelatonin binding) [18]. The affinity and potency of various synthetic melatonin receptor agonists and antagonists in heterologous cell lines using cell based assays (e.g., forskolin-stimulated cAMP accumulation; [35S]GTPγS binding). The MT2 receptors can exhibit a constitutive, non melatonin-induced signaling activity in two cellular models of different origins, the Chinese hamster ovary cell line and Neuro2A, a neuroblastoma cell line. In the same study, the melatonin inverse agonists (UCM 549 and UCM 724) were reported [11].

Activation of human recombinant melatonin receptors inhibits cAMP and cGMP formation [47-48,50]. MT2 receptor expression by RT-PCR and in situ hybridization suggests that this receptor may be expressed in mammalian retina, selected brain areas and some arterial beds [19,37,48,62]. The availability of selective MT2 receptor antagonists (4P-PDOT, 4P-ADOT) has led to the identification of functional MT2 melatonin receptors in retina (inhibition of dopamine release) [18], in the circadian timing system (phase shifting of circadian rhythms) [16,37], and in rat caudal artery (vasodilation) [12,40]. Using mice with genetic deletion of the MT2 melatonin receptor the following functions for this receptor have been demonstrated: a) phase shift of the peak of the circadian rhythm of neuronal firing (suprachiasmatic nucleus; [16,37]); b) inhibition dopamine release (rabbit retina; [18]); c) inhibition insuline relase (pancreatic islets; [44]) and others.

Genome-wide association studies identified frequent variants upstream of exon 1 or within the single intron of the MTNR1B gene coding for the MT2 receptor that associated with increased fasting plasma glucose levels and type 2 diabetes risk [33].

MT1/MT2 heteromers

GPCRs MT1 and MT2 receptors exist typically as monomers and homomers (di-, oligomers) when expressed individually. When expressed in the same cell MT1 and MT2 receptors have been shown to form also MT1/MT2 heteromers. This has been first shown in vitro [3-4] and then in vivo in retinal photoreceptor cells where they mediated the effect of melatonin on light sensitivity of rod photoreceptors in mice [5]. This effect of melatonin involved activation of the heteromer-specific phospholipase C and protein kinase C (PLC/PKC) pathway and was abolished in MT1 KO or MT2 KO mice, as well as in mice overexpressing a nonfunctional MT2 mutant that interfered with the formation of functional MT1/MT2 heteromers in photoreceptor cells. A leftward shift of the EC50 value of inhibition of cAMP production by melatonin was observed in cells expressing MT1/MT2 heteromers as compared to the corresponding homomers in transfected HEK293 cells.

References

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1. Al-Ghoul WM, Herman MD, Dubocovich ML. (1998) Melatonin receptor subtype expression in human cerebellum. Neuroreport, 9 (18): 4063-8. [PMID:9926848]

2. Audinot V, Mailliet F, Lahaye-Brasseur C, Bonnaud A, Le Gall A, Amossé C, Dromaint S, Rodriguez M, Nagel N, Galizzi JP et al.. (2003) New selective ligands of human cloned melatonin MT1 and MT2 receptors. Naunyn Schmiedebergs Arch. Pharmacol., 367 (6): 553-61. [PMID:12764576]

3. Ayoub MA, Couturier C, Lucas-Meunier E, Angers S, Fossier P, Bouvier M, Jockers R. (2002) Monitoring of ligand-independent dimerization and ligand-induced conformational changes of melatonin receptors in living cells by bioluminescence resonance energy transfer. J. Biol. Chem., 277 (24): 21522-8. [PMID:11940583]

4. Ayoub MA, Levoye A, Delagrange P, Jockers R. (2004) Preferential formation of MT1/MT2 melatonin receptor heterodimers with distinct ligand interaction properties compared with MT2 homodimers. Mol. Pharmacol., 66 (2): 312-21. [PMID:15266022]

5. Baba K, Benleulmi-Chaachoua A, Journé AS, Kamal M, Guillaume JL, Dussaud S, Gbahou F, Yettou K, Liu C, Contreras-Alcantara S et al.. (2013) Heteromeric MT1/MT2 melatonin receptors modulate photoreceptor function. Sci Signal, 6 (296): ra89. [PMID:24106342]

6. Barrett P, Conway S, Jockers R, Strosberg AD, Guardiola-Lemaitre B, Delagrange P, Morgan PJ. (1997) Cloning and functional analysis of a polymorphic variant of the ovine Mel 1a melatonin receptor. Biochim. Biophys. Acta, 1356 (3): 299-307. [PMID:9194573]

7. Browning C, Beresford I, Fraser N, Giles H. (2000) Pharmacological characterization of human recombinant melatonin mt(1) and MT(2) receptors. Br. J. Pharmacol., 129 (5): 877-86. [PMID:10696085]

8. Conway S, Drew JE, Canning SJ, Barrett P, Jockers R, Strosberg AD, Guardiola-Lemaitre B, Delagrange P, Morgan PJ. (1997) Identification of Mel1a melatonin receptors in the human embryonic kidney cell line HEK293: evidence of G protein-coupled melatonin receptors which do not mediate the inhibition of stimulated cyclic AMP levels. FEBS Lett., 407 (1): 121-6. [PMID:9141494]

9. Copinga S, Tepper PG, Grol CJ, Horn AS, Dubocovich ML. (1993) 2-Amido-8-methoxytetralins: a series of nonindolic melatonin-like agents. J. Med. Chem., 36 (20): 2891-8. [PMID:8411005]

10. Depreux P, Lesieur D, Mansour HA, Morgan P, Howell HE, Renard P, Caignard DH, Pfeiffer B, Delagrange P, Guardiola B et al.. (1994) Synthesis and structure-activity relationships of novel naphthalenic and bioisosteric related amidic derivatives as melatonin receptor ligands. J. Med. Chem., 37 (20): 3231-9. [PMID:7932550]

11. Devavry S, Legros C, Brasseur C, Delagrange P, Spadoni G, Cohen W, Malpaux B, Boutin JA, Nosjean O. (2012) Description of the constitutive activity of cloned human melatonin receptors hMT(1) and hMT(2) and discovery of inverse agonists. J. Pineal Res., 53 (1): 29-37. [PMID:22017484]

12. Doolen S, Krause DN, Dubocovich ML, Duckles SP. (1998) Melatonin mediates two distinct responses in vascular smooth muscle. Eur. J. Pharmacol., 345 (1): 67-9. [PMID:9593596]

13. Dubocovich ML. (1988) Pharmacology and function of melatonin receptors. FASEB J., 2 (12): 2765-73. [PMID:2842214]

14. Dubocovich ML. (1995) Melatonin receptors: are there multiple subtypes?. Trends Pharmacol. Sci., 16 (2): 50-6. [PMID:7762083]

15. Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J. (2010) International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol. Rev., 62 (3): 343-80. [PMID:20605968]

16. Dubocovich ML, Hudson RL, Sumaya IC, Masana MI, Manna E. (2005) Effect of MT1 melatonin receptor deletion on melatonin-mediated phase shift of circadian rhythms in the C57BL/6 mouse. J. Pineal Res., 39 (2): 113-20. [PMID:16098087]

17. Dubocovich ML, Masana MI. (1998) The efficacy of melatonin receptor analogues is dependent on the level of human melatonin receptor subtype expression. In Biological Clocks, Mechanisms and Applications. Edited by Touitou Y (Elsevier Science B. V.) 289-293. [ISBN:0444825037]

18. Dubocovich ML, Masana MI, Iacob S, Sauri DM. (1997) Melatonin receptor antagonists that differentiate between the human Mel1a and Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor. Naunyn Schmiedebergs Arch. Pharmacol., 355 (3): 365-75. [PMID:9089668]

19. Dubocovich ML, Yun K, Al-Ghoul WM, Benloucif S, Masana MI. (1998) Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms. FASEB J., 12 (12): 1211-20. [PMID:9737724]

20. Duncan MJ, Takahashi JS, Dubocovich ML. (1988) 2-[125I]iodomelatonin binding sites in hamster brain membranes: pharmacological characteristics and regional distribution. Endocrinology, 122 (5): 1825-33. [PMID:2834175]

21. Duncan MJ, Takahashi JS, Dubocovich ML. (1989) Characteristics and autoradiographic localization of 2-[125I]iodomelatonin binding sites in Djungarian hamster brain. Endocrinology, 125 (2): 1011-8. [PMID:2752961]

22. Eison AS, Mullins UL. (1993) Melatonin binding sites are functionally coupled to phosphoinositide hydrolysis in Syrian hamster RPMI 1846 melanoma cells. Life Sci., 53 (24): PL393-8. [PMID:8246675]

23. Erşahin C, Masana MI, Dubocovich ML. (2002) Constitutively active melatonin MT(1) receptors in male rat caudal arteries. Eur. J. Pharmacol., 439 (1-3): 171-2. [PMID:11937107]

24. Faust R, Garratt PJ, Jones R, Yeh LK, Tsotinis A, Panoussopoulou M, Calogeropoulou T, Teh MT, Sugden D. (2000) Mapping the melatonin receptor. 6. Melatonin agonists and antagonists derived from 6H-isoindolo[2,1-a]indoles, 5,6-dihydroindolo[2,1-a]isoquinolines, and 6,7-dihydro-5H-benzo[c]azepino[2,1-a]indoles. J. Med. Chem., 43 (6): 1050-61. [PMID:10737738]

25. Flaugh ME, Crowell TA, Clemens JA, Sawyer BD. (1979) Synthesis and evaluation of the antiovulatory activity of a variety of melatonin analogues. J. Med. Chem., 22 (1): 63-9. [PMID:423184]

26. Garratt PJ, Jones R, Tocher DA, Sugden D. (1995) Mapping the melatonin receptor. 3. Design and synthesis of melatonin agonists and antagonists derived from 2-phenyltryptamines. J. Med. Chem., 38 (7): 1132-9. [PMID:7707316]

27. Garratt PJ, Travard S, Vonhoff S, Tsotinis A, Sugden D. (1996) Mapping the melatonin receptor. 4. Comparison of the binding affinities of a series of substituted phenylalkyl amides. J. Med. Chem., 39 (9): 1797-805. [PMID:8627603]

28. Garrett PJ, Jones R, Rowe SJ, Sugden D. (1994) Mapping the melatonin receptor. 1. The 5-methoxyl group of melatonin is not an essential requirement for biological activity. Bioorg. Med. Chem. Lett., 4: 1555-1558.

29. Garrett PJ, Vonhoff S, Rowe S, Sugden D. (1994) Mapping of the melatonin receptor. 2. Synthesis and biological activity of indole derived melatonin analogues with restricted conformations of the C-3 amido ethane side chain. Bioorg. Med. Chem. Lett., 4: 1559-1564.

30. Godson C, Reppert SM. (1997) The Mel1a melatonin receptor is coupled to parallel signal transduction pathways. Endocrinology, 138 (1): 397-404. [PMID:8977429]

31. Hagan RM, Oakley NR. (1995) Melatonin comes of age?. Trends Pharmacol. Sci., 16 (3): 81-3. [PMID:7792932]

32. Jockers R, Maurice P, Boutin JA, Delagrange P. (2008) Melatonin receptors, heterodimerization, signal transduction and binding sites: what's new?. Br. J. Pharmacol., 154 (6): 1182-95. [PMID:18493248]

33. Karamitri A, Renault N, Clement N, Guillaume JL, Jockers R. (2013) Minireview: Toward the establishment of a link between melatonin and glucose homeostasis: association of melatonin MT2 receptor variants with type 2 diabetes. Mol. Endocrinol., 27 (8): 1217-33. [PMID:23798576]

34. Kato K, Hirai K, Nishiyama K, Uchikawa O, Fukatsu K, Ohkawa S, Kawamata Y, Hinuma S, Miyamoto M. (2005) Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist. Neuropharmacology, 48 (2): 301-10. [PMID:15695169]

35. Krause DN, Barrios VE, Duckles SP. (1995) Melatonin receptors mediate potentiation of contractile responses to adrenergic nerve stimulation in rat caudal artery. Eur. J. Pharmacol., 276 (3): 207-13. [PMID:7601206]

36. Krause DN, Dubocovich ML. (1990) Regulatory sites in the melatonin system of mammals. Trends Neurosci., 13: 464-470. [PMID:1701580]

37. Liu C, Weaver DR, Jin X, Shearman LP, Pieschl RL, Gribkoff VK, Reppert SM. (1997) Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron, 19 (1): 91-102. [PMID:9247266]

38. Mailliet F, Ferry G, Vella F, Thiam K, Delagrange P, Boutin JA. (2004) Organs from mice deleted for NRH:quinone oxidoreductase 2 are deprived of the melatonin binding site MT3. FEBS Lett, 578: 116-120. [PMID:15581627]

39. Markus RP, Cecon E, Pires-Lapa MA. (2013) Immune-Pineal Axis: Nuclear Factor κB (NF-kB) Mediates the Shift in the Melatonin Source from Pinealocytes to Immune Competent Cells. Int J Mol Sci, 14 (6): 10979-97. [PMID:23708099]

40. Masana MI, Doolen S, Ersahin C, Al-Ghoul WM, Duckles SP, Dubocovich ML, Krause DN. (2002) MT(2) melatonin receptors are present and functional in rat caudal artery. J Pharmacol Exp Ther, 302: 1295-1302. [PMID:12183692]

41. Molinari EJ, North PC, Dubocovich ML. (1996) 2-[125I]iodo-5-methoxycarbonylamino-N-acetyltryptamine: a selective radioligand for the characterization of melatonin ML2 binding sites. Eur. J. Pharmacol., 301 (1-3): 159-68. [PMID:8773460]

42. Morgan PJ, Barrett P, Howell HE, Helliwell R. (1994) Melatonin receptors: localization, molecular pharmacology and physiological significance. Neurochem. Int., 24 (2): 101-46. [PMID:8161940]

43. Mulchahey JJ, Goldwater DR, Zemlan FP. (2004) A single blind, placebo controlled, across groups dose escalation study of the safety, tolerability, pharmacokinetics and pharmacodynamics of the melatonin analog beta-methyl-6-chloromelatonin. Life Sci., 75 (15): 1843-56. [PMID:15302228]

44. Mühlbauer E, Gross E, Labucay K, Wolgast S, Peschke E. (2009) Loss of melatonin signalling and its impact on circadian rhythms in mouse organs regulating blood glucose. Eur. J. Pharmacol., 606 (1-3): 61-71. [PMID:19374844]

45. Nonno R, Lucini V, Spadoni G, Pannacci M, Croce A, Esposti D, Balsamini C, Tarzia G, Fraschini F, Stankov BM. (2000) A new melatonin receptor ligand with mt1-agonist and MT2-antagonist properties. J. Pineal Res., 29 (4): 234-40. [PMID:11068946]

46. Nosjean O, Ferro M, Coge F, Beauverger P, Henlin JM, Lefoulon F, Fauchere JL, Delagrange P, Canet E, Boutin JA. (2000) Identification of the melatonin-binding site MT3 as the quinone reductase 2. J. Biol. Chem., 275 (40): 31311-7. [PMID:10913150]

47. Petit L, Lacroix I, de Coppet P, Strosberg AD, Jockers R. (1999) Differential signaling of human Mel1a and Mel1b melatonin receptors through the cyclic guanosine 3'-5'-monophosphate pathway. Biochem. Pharmacol., 58 (4): 633-9. [PMID:10413300]

48. Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF. (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): 8734-8. [PMID:7568007]

49. Reppert SM, Weaver DR, Cassone VM, Godson C, Kolakowski Jr LF. (1995) Melatonin receptors are for the birds: molecular analysis of two receptor subtypes differentially expressed in chick brain. Neuron, 15 (5): 1003-15. [PMID:7576645]

50. Reppert SM, Weaver DR, Ebisawa T. (1994) Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron, 13 (5): 1177-85. [PMID:7946354]

51. Reppert SM, Weaver DR, Godson C. (1996) Melatonin receptors step into the light: cloning and classification of subtypes. Trends Pharmacol. Sci., 17 (3): 100-2. [PMID:8936344]

52. Rivara S, Mor M, Bedini A, Spadoni G, Tarzia G. (2008) Melatonin receptor agonists: SAR and applications to the treatment of sleep-wake disorders. Curr Top Med Chem, 8 (11): 954-68. [PMID:18673165]

53. Roka F, Brydon L, Waldhoer M, Strosberg AD, Freissmuth M, Jockers R, Nanoff C. (1999) Tight association of the human Mel(1a)-melatonin receptor and G(i): precoupling and constitutive activity. Mol. Pharmacol., 56 (5): 1014-24. [PMID:10531408]

54. Savaskan E, Olivieri G, Brydon L, Jockers R, Kräuchi K, Wirz-Justice A, Müller-Spahn F. (2001) Cerebrovascular melatonin MT1-receptor alterations in patients with Alzheimer's disease. Neurosci. Lett., 308 (1): 9-12. [PMID:11445273]

55. Savaskan E, Wirz-Justice A, Olivieri G, Pache M, Kräuchi K, Brydon L, Jockers R, Müller-Spahn F, Meyer P. (2002) Distribution of melatonin MT1 receptor immunoreactivity in human retina. J. Histochem. Cytochem., 50 (4): 519-26. [PMID:11897804]

56. Scher J, Wankiewicz E, Brown GM, Fujieda H. (2002) MT(1) melatonin receptor in the human retina: expression and localization. Invest. Ophthalmol. Vis. Sci., 43 (3): 889-97. [PMID:11867612]

57. Scher J, Wankiewicz E, Brown GM, Fujieda H. (2003) AII amacrine cells express the MT1 melatonin receptor in human and macaque retina. Exp. Eye Res., 77 (3): 375-82. [PMID:12907170]

58. Slaugenhaupt SA, Roca AL, Liebert CB, Altherr MR, Gusella JF, Reppert SM. (1995) Mapping of the gene for the Mel1a-melatonin receptor to human chromosome 4 (MTNR1A) and mouse chromosome 8 (Mtnr1a). Genomics, 27 (2): 355-7. [PMID:7558006]

59. Soares Jr JM, Masana MI, Erşahin C, Dubocovich ML. (2003) Functional melatonin receptors in rat ovaries at various stages of the estrous cycle. J. Pharmacol. Exp. Ther., 306 (2): 694-702. [PMID:12721330]

60. Spadoni G, Stankov B, Duranti A, Biella G, Lucini V, Salvatori A, Fraschini F. (1993) 2-Substituted 5-methoxy-N-acyltryptamines: synthesis, binding affinity for the melatonin receptor, and evaluation of the biological activity. J. Med. Chem., 36 (25): 4069-74. [PMID:8258829]

61. Teh MT, Sugden D. (1999) The putative melatonin receptor antagonist GR128107 is a partial agonist on Xenopus laevis melanophores. Br. J. Pharmacol., 126 (5): 1237-45. [PMID:10205014]

62. Ting KN, Blaylock NA, Sugden D, Delagrange P, Scalbert E, Wilson VG. (1999) Molecular and pharmacological evidence for MT1 melatonin receptor subtype in the tail artery of juvenile Wistar rats. Br J Pharmacol, 127: 987-995. [PMID:10433507]

63. Ting KN, Dunn WR, Davies DJ, Sugden D, Delagrange P, Guardiola-Lemaître B, Scalbert E, Wilson VG. (1997) Studies on the vasoconstrictor action of melatonin and putative melatonin receptor ligands in the tail artery of juvenile Wistar rats. Br. J. Pharmacol., 122 (7): 1299-306. [PMID:9421275]

64. Tosini G, Owino S, Guillaume JL, Jockers R. (2014) Understanding melatonin receptor pharmacology: latest insights from mouse models, and their relevance to human disease. Bioessays, 36 (8): 778-87. [PMID:24903552]

65. Yasuo S, Yoshimura T, Ebihara S, Korf HW. (2009) Melatonin transmits photoperiodic signals through the MT1 melatonin receptor. J. Neurosci., 29 (9): 2885-9. [PMID:19261884]

66. Yous S, Andrieux J, Howell HE, Morgan PJ, Renard P, Pfeiffer B, Lesieur D, Guardiola-Lemaitre B. (1992) Novel naphthalenic ligands with high affinity for the melatonin receptor. J. Med. Chem., 35 (8): 1484-6. [PMID:1315395]

67. Zlotos DP, Jockers R, Cecon E, Rivara S, Witt-Enderby PA. (2014) MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J. Med. Chem., 57 (8): 3161-85. [PMID:24228714]

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