Characterisation of human melatonin mt1 and MT2 receptors by CRE-luciferase reporter assay

Conway, Shaun; Canning, Sarah J.; Howell, H. E.; Mowat, Elaine S.; Barrett, Perry; Drew, Janice E.; Delagrange, P; Lesieur, D.; Morgan, Peter J.

doi:10.1016/s0014-2999(99)00914-0

Cited by 61 publications

(42 citation statements)

References 29 publications

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“…Neuropsychopharmacology Antidepressant activity of agomelatine in chronic mild stress M Papp et al effects in control animals), and time course (4-5 weeks of treatment required to reverse the deficit in sucrose consumption). However, the main finding of the present study is that the CMS-induced reduction in the intake of sweet solution can be normalized by chronic administration of agomelatine (S 20098), a potent agonist of melatonin MT 1 and MT 2 receptors (Yous et al, 1992;Ying et al, 1996;Conway et al, 2000) and an antagonist of the 5-HT 2C receptors (Cussac et al, 2002).…”

Section: Discussionmentioning

confidence: 69%

“…As mentioned earlier, apart from its agonistic properties at melatonin MT 1 and MT 2 receptors (Yous et al, 1992;Ying et al, 1996;Conway et al, 2000), agomelatine has also a potent antagonistic activity at 5-HT 2C receptors (Cussac et al, 2002) and numerous findings indicate that reduced function of 5-HT 2C receptors may be involved in the mechanism by which antidepressants alleviate depression (see Sanchez and Hyttel, 1999). Moreover, the unselective 5-HT 2 antagonist mianserin is an effective antidepressant (Brogden et al, 1978;Montgomery, 1980;De Ridder, 1982), and efficacy of the 5-HT 2A/2C antagonist ritanserin has also been shown in some clinical trials (Strauss and Klieser, 1991).…”

Section: Discussionmentioning

confidence: 96%

“…Agomelatine (S 20098; N(2-(7-methoxy-1-naphthyl)ethyl) acetamide) is a potent agonist of melatonin receptors (Yous et al, 1992;Ying et al, 1996;Conway et al, 2000) and an antagonist of the 5-HT 2C receptor subtype (Cussac et al, 2002). Agomelatine shows a high affinity for cloned human receptors MT 1 and MT 2 subtypes (K i ¼ 6.15 Â 10 À11 and 2.68 Â 10 À10 M, respectively) as well as for the 5-HT 2C receptor (IC 50 ¼ 2.7 Â 10 À7 M on human cloned 5-HT 2C receptors).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Agomelatine in the Chronic Mild Stress Model of Depression in the Rat

Papp

Gruca

Boyer

et al. 2002

Neuropsychopharmacol

243

166

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Chronic mild stress (CMS), a well-validated model of depression, was used to study the effects of the melatonin agonist and selective 5-HT 2C antagonist agomelatine (S 20098) in comparison with melatonin, imipramine, and fluoxetine. All drugs were administered either 2 h before (evening treatment) or 2 h after (morning treatment) the dark phase of the 12-h light/dark cycle. Chronic (5 weeks) evening treatment with agomelatine or melatonin (both at 10 and 50 mg/kg i.p.) dose-dependently reversed the CMS-induced reduction in sucrose consumption. The magnitude and time course of the action of both drugs was comparable to that of imipramine and fluoxetine (both at 10 mg/kg i.p.); however, melatonin was less active than agomelatine at this dose. The effect of evening administration of agomelatine and melatonin was completely inhibited by an acute injection of the MT 1 /MT 2 antagonist, S 22153 (20 mg/kg i.p.), while the antagonist had no effect in animals receiving fluoxetine or imipramine. When the drugs were administered in the morning, agomelatine caused effects similar to those observed after evening treatment (with onset of action faster than imipramine) but melatonin was ineffective. Moreover, melatonin antagonist, S 22153, did not modify the intakes in stressed animals receiving morning administration of agomelatine and in any other control and stressed groups tested in this study. These data demonstrate antidepressant-like activity of agomelatine in the rat CMS model of depression, which was independent of the time of drug administration. The efficacy of agomelatine is comparable to that of imipramine and fluoxetine, but greater than that of melatonin, which had no antidepressant-like activity after morning administration. While the evening efficacy of agomelatine can be related to its melatonin receptors agonistic properties, its morning activity, which was not inhibited by a melatonin antagonist, indicates that these receptors are certainly required, but not sufficient to sustain the agomelatine efficacy. It is therefore suggested that the antidepressant-like activity of agomelatine depends on some combination of its melatonin agonist and 5-HT 2C antagonist properties.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Agomelatine in the Chronic Mild Stress Model of Depression in the Rat

Papp

Gruca

Boyer

et al. 2002

Neuropsychopharmacol

243

166

View full text Add to dashboard Cite

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“…sion and/or oligomerization may influence secondmessenger signaling (Brydon et al, 1999;Conway et al, 2000;Masana and Dubocovich, 2001).…”

Section: Discussionmentioning

confidence: 99%

Functional melatonin receptors and metabolic coupling in cultured chick astrocytes

Adachi

Natesan

Whitfield-Rucker

et al. 2002

Glia

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Melatonin is an important hormone regulating circadian clocks in birds, but the specific cellular sites of action are not completely known. The present study was designed to determine whether astrocytes derived from chick brain contained functional melatonin receptors. Primary cell cultures of diencephalon astrocytes that express glial fibrillary acidic protein (GFAP), but not neuron-specific enolase (NSE) immunoreactivity, were employed to determine the cellular distribution and physiological role for the three known receptor subtypes. Saturation and Scatchard analysis of 2-[(125)I]iodomelatonin binding demonstrated melatonin receptor binding with a high affinity and a pharmacological profile similar to that obtained from brain. In situ hybridization for receptor subtypes revealed Mel(1A) and Mel(1C) receptor mRNA, but not Mel(1B). Administration of pharmacological levels of melatonin acutely inhibited forskolin-stimulated 2-deoxyglucose (2DG) uptake, while rhythmic administration of physiological levels of melatonin gradually imposed a rhythm in 2DG uptake and of the release of both lactate and pyruvate into the medium. These results indicate that (1) there are functional Mel(1A) and Mel(1C) melatonin receptors in astrocyte-rich cultures, and (2) rhythmic administration of melatonin plays an important role in the regulation of astrocytic metabolic activity. Together, the data suggest that the circadian secretion of melatonin probably plays a role in the global metabolic economy of the avian brain through rhythmic regulation of metabolism in astrocytes.

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“…Firefly luciferase gene (luc) is one of the most commonly used for this purpose, since it provides a high detectability and can be measured in living cells. Luminescent cell-based assays have been used to assess the activity of compounds targeted at various receptors [17,18,19,20,21,22]. We have developed an assay that allows screening the activity of bile acids on the farnesoid X receptor (FXR), which is involved in bile acid and cholesterol homeostasis [23,24].…”

Section: Cell-based Assaysmentioning

confidence: 99%

Bioluminescence and chemiluminescence in drug screening

Roda

Guardigli

Pasini

et al. 2003

Analytical and Bioanalytical Chemistry

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Drug screening, that is, the evaluation of the biological activity of candidate drug molecules, is a key step in the drug discovery and development process. In recent years, high-throughput screening assays have become indispensable for early stage drug discovery because of the developments in synthesis technologies, such as combinatorial chemistry and automated synthesis, and the discovery of an increasing number of new pharmacological targets. Bioluminescence and chemiluminescence represent suitable detection techniques for high-throughput screening because they allow rapid and sensitive detection of the analytes and can be applied to small-volume samples. In this paper we report on recent applications of bioluminescence and chemiluminescence in drug screening, both for in vitro and in vivo assays. Particular attention is devoted to the latest and most innovative bioluminescence and chemiluminescence-based technologies for drug screening, such as assays based on genetically modified cells, bioluminescence resonance energy transfer (BRET)-based assays, and in vivo imaging assays using transgenic animals or bioluminescent markers. The possible relevance of bioluminescence and chemiluminescence techniques in the future developments of high-throughput screening technologies is also discussed.

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Characterisation of human melatonin mt1 and MT2 receptors by CRE-luciferase reporter assay

Cited by 61 publications

References 29 publications

Effect of Agomelatine in the Chronic Mild Stress Model of Depression in the Rat

Effect of Agomelatine in the Chronic Mild Stress Model of Depression in the Rat

Functional melatonin receptors and metabolic coupling in cultured chick astrocytes

Bioluminescence and chemiluminescence in drug screening

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