Cloning of a melatonin‐related receptor from human pituitary

Reppert, Steven M.; Weaver, David R.; Ebisawa, Takashi; Mahle, Cathy D.; Kolakowski, Lee F.

doi:10.1016/0014-5793(96)00437-1

Cited by 149 publications

(137 citation statements)

References 19 publications

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“…5,[10][11][12][13] GPR50 is an X-linked orphan G protein-coupled receptor (also known as H9, melatonin-related receptor or ML1X) located on Xq28, and was initially cloned from a human pituitary cDNA library. 14,15 The gene encodes a protein of 617 amino acids that is 45% identical overall to human melatonin receptors MTNR1A and MTNR1B , with identity increasing to 55% when comparing just the transmembrane domains. 15 Despite its close structural relationship to the melatonin receptors, GPR50 does not bind either [ 125 I]melatonin or [ 3 H]melatonin.…”

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confidence: 99%

“…14,15 The gene encodes a protein of 617 amino acids that is 45% identical overall to human melatonin receptors MTNR1A and MTNR1B , with identity increasing to 55% when comparing just the transmembrane domains. 15 Despite its close structural relationship to the melatonin receptors, GPR50 does not bind either [ 125 I]melatonin or [ 3 H]melatonin. 15,16 RNA in situ hybridisation experiments with human GPR50 detected expression in the mediobasal hypothalamus, in a region containing the ventromedial and arcuate nuclei; and the paraventricular nucleus, as well as in the infundibular stalk.…”

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confidence: 99%

“…15 Despite its close structural relationship to the melatonin receptors, GPR50 does not bind either [ 125 I]melatonin or [ 3 H]melatonin. 15,16 RNA in situ hybridisation experiments with human GPR50 detected expression in the mediobasal hypothalamus, in a region containing the ventromedial and arcuate nuclei; and the paraventricular nucleus, as well as in the infundibular stalk. 15 Expression was also detected in the pituitary gland.…”

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confidence: 99%

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Sex-specific association between bipolar affective disorder in women and GPR50, an X-linked orphan G protein-coupled receptor

Thomson

Wray

Thomson³

et al. 2004

Mol Psychiatry

105

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GPR50 is an orphan G protein-coupled receptor (GPCR) located on Xq28, a region previously implicated in multiple genetic studies of bipolar affective disorder (BPAD). Allele frequencies of three polymorphisms in GPR50 were compared in case-control studies between subjects with BPAD (264), major depressive disorder (MDD) (226), or schizophrenia (SCZ) (263) and ethnically matched controls (562). Significant associations were found between an insertion/ deletion polymorphism in exon 2 and both BPAD (P ¼ 0.0070), and MDD (P ¼ 0.011) with increased risk associated with the deletion variant (GPR50 D502-505 ). When the analysis was restricted to female subjects, the associations with BPAD and MDD increased in significance (P ¼ 0.00023 and P ¼ 0.0064, respectively). Two other single-nucleotide polymorphisms (SNPs) tested within this gene showed associations between: the female MDD group and an SNP in exon 2 (P ¼ 0.0096); and female SCZ and an intronic SNP (P ¼ 0.0014). No association was detected in males with either MDD, BPAD or SCZ. These results suggest that GPR50 D502-505 , or a variant in tight linkage disequilibrium with this polymorphism, is a sex-specific risk factor for susceptibility to bipolar disorder, and that other variants in the gene may be sex-specific risk factors in the development of schizophrenia. Bipolar affective disorder (BPAD) is a severe psychiatric disorder affecting approximately 1% of the world's population, and shows no difference in lifetime prevalence between male and female subjects. Twin and adoption studies have demonstrated a strong genetic component, with a concordance in BPAD between monozygotic twins of 60%. 1 Major depressive disorder (MDD) has a lifetime prevalence of 17% with women twice as likely as men to develop the disorder. 2 Estimates of the heritability of MDD vary, but a meta-analysis of studies gives a point estimate of heritability of liability to MDD of 0.37. 3 Schizophrenia (SCZ), as with BPAD, has an estimated frequency of 1% in the population, but heritability estimates suggest that it has a larger genetic component than either BPAD or MDD, with monozygotic twins giving a point estimate of comorbidity of 0.81 in another recent meta-analysis. 4 Despite the strong genetic component in these major psychiatric disorders, there are also strong environmental influences.Linkage to Xq28 has been studied many times in BPAD. Two loci, colour-blindness (CB), and glucose-6-phosphate dehydrogenase (G6PD), have been detected through linkage and association in more than one population. 5 Most significant are LOD scores of 8.1 and 7.35 between CB and BPAD in the American and Belgian populations, respectively, although reanalysis of much of the data from positive linkage results on the X chromosome has resulted in much reduced evidence for linkage and suggestions of ascertainment bias. 6-9 Several more recent studies have again renewed interest in the distal end of Xq, although the region implicated in these studies (Xq24-28) is larger than that depicted in the earlier reports. 5,[...

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confidence: 99%

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Sex-specific association between bipolar affective disorder in women and GPR50, an X-linked orphan G protein-coupled receptor

Thomson

Wray

Thomson³

et al. 2004

Mol Psychiatry

105

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“…Daily variation in 2-[ 125 I]-melatonin binding sites in the golden hamster retina (Faillace et al, 1995) has been reported. Melatonin receptors were cloned in mammals (Reppert et al, 1994(Reppert et al, , 1996, and these authors showed that the distribution of melatonin receptor mRNA is coincident with that of 2-[ 125 I]-melatonin binding.…”

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Daily morphological variations in the viscacha (Lagostomus maximus maximus) retina. Probable local modulatory action of melatonin

Calderón¹,

Mohamed²,

Muñoz³

et al. 2002

Anat. Rec.

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Given that the local melatonin levels exhibit rhythmic daily changes in the retina of the viscacha, we considered it important to study the likely daily variations in morphology and specific 2-[ 125 I]-iodomelatonin binding in retinas from this rodent and to correlate these putative changes with local indole levels. Adult animals of both sexes were captured in their habitat and were kept under a natural photoperiod. For light and electron microscopic studies the viscachas were sacrificed by decapitation at 08:00, 16:00, and 24:00 hr. A computer-assisted image analysis system was used to measure the thickness of the complete retina, the photoreceptor layer, the rod outer and inner segments, and the outer nuclear layer. The daily variation in 2-[ 125 I]-iodomelatonin binding sites was followed during a 24-hr light-dark cycle, the animals being sacrificed at six time points. The parameters studied showed significant variations throughout the 24-hr period. Maximal specific binding, lysosomal content in the pigment epithelium, and photoreceptor layer outer segment thicknesses were observed at 24:00 hr. Close contact between photoreceptor membranes and microvilli of the pigment epithelium was observed at 08:00 and 16:00 hr. Moreover, the minimal outer segment thickness at 16:00 hr was accompanied by a scarcity of dense bodies, such as lysosomes, a maximum dispersion of melanin pigment granules, and a minimum density of radioligand binding sites. Therefore, in the retina of the viscacha, we suggest that the interaction between melatonin and specific sites could be one of the factors or causes that participate in the regulation of the daily morphological changes observed in viscacha.

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“…Les récepteurs MT 1 et MT 2 sont impliqués dans le contrôle du rythme circadien, dans des phénomènes vasoactifs et également dans la reproduction. La forte homologie de GPR50 avec les récepteurs MT 1 et MT 2 de la mélatonine a permis de classer ce récepteur au sein de cette famille et suggérait un ligand naturel proche de la méla-tonine pour ce récepteur [37]. Cependant, les études pharmacologiques n'ont montré aucune spécificité de liaison pour les différents ligands mélatoninergiques connus, lui conférant ainsi son caractère orphelin.…”

Section: Gpr50 : Un Récepteur Orphelin à 7tm De La Famille Rhodopsineunclassified

L’hétérodimérisation des récepteurs couplés aux protéines G

Levoye

Jockers

2007

Med Sci (Paris)

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Cloning of a melatonin‐related receptor from human pituitary

Cited by 149 publications

References 19 publications

Sex-specific association between bipolar affective disorder in women and GPR50, an X-linked orphan G protein-coupled receptor

Sex-specific association between bipolar affective disorder in women and GPR50, an X-linked orphan G protein-coupled receptor

Daily morphological variations in the viscacha (Lagostomus maximus maximus) retina. Probable local modulatory action of melatonin

L’hétérodimérisation des récepteurs couplés aux protéines G

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