Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Br J Pharmacol
1999 Mar 01;1265:1237-45. doi: 10.1038/sj.bjp.0702404.
Show Gene links
Show Anatomy links
The putative melatonin receptor antagonist GR128107 is a partial agonist on Xenopus laevis melanophores.
Teh MT
,
Sugden D
.
???displayArticle.abstract???
1. GR128107 (3-(1-acetyl-3-methyl-piperidine)-5-methoxyindole) has previously been reported to be a competitive melatonin receptor antagonist in blocking melatonin inhibition of [3H]-dopamine release from rabbit retina, a response mediated by the MT2 receptor subtype. 2. GR128107, like melatonin, induced a rapid (maximum response in 60-90 min) pigment aggregation in a clonal line of Xenopus laevis melanophores. GR128107 behaved as a partial agonist (pEC50 8.58+/-0.03, n=3) with an Emax of 0.83 (relative to melatonin, pEC50 10.09+/-0.03, n=3). 3. The concentration-response curve for pigment granule aggregation to both melatonin and GR128107 was displaced in a parallel, rightward manner by melatonin receptor antagonists with very similar potencies; estimated pKB RJ252 (against melatonin 4.60/against GR128107 4.54) < GR135533 (6.40/6.14) < Luzindole (6.45/6.49) < S20929 (6.58/6.65) < 4-P-PDOT (6.73/6.85). 4. Both melatonin- and GR128107-induced pigment granule aggregation was prevented by pretreatment of melanophores with pertussis toxin (10-1000 ng ml(-1)). 5. Prolonged pre-treatment of melanophores with melatonin desensitized the pigment aggregation response to GR128107. In desensitized cells, the maximal aggregation produced by GR128107 was only 0.27+/-0.01 (n=4) and the pEC50 was reduced (vehicle 8.57+/-0.12; melatonin pre-treated 7.84+/-0.09, n=4). The maximal response to melatonin in desensitized melanophores was unchanged but the pEC50 was reduced (vehicle 10.49+/-0.03; melatonin pre-treated 9.83+/-0.04, n=4). 6. These results demonstrate that GR128107 induces pigment granule aggregation in Xenopus melanophores by activating a cell membrane melatonin receptor coupled via a pertussis toxin-sensitive G-protein. 7. The partial agonist activity of GR128107 in melanophores may be apparent because of the very high density of melatonin receptors in these cells (Bmax 1223 fmol mg protein(-1)) compared to the low density of sites in rabbit retina (Bmax 3.1 fmol mg protein(-1)). This suggestion is supported by the finding that GR128107, like melatonin, acted as a full agonist and inhibited forskolin-stimulation of cyclic AMP accumulation in NIH-3T3 cells expressing a high density of human mt1 or MT2 receptors.
Arendt,
Melatonin and the pineal gland: influence on mammalian seasonal and circadian physiology.
1998, Pubmed
Arendt,
Melatonin and the pineal gland: influence on mammalian seasonal and circadian physiology.
1998,
Pubmed
Armstrong,
Melatonin and circadian control in mammals.
1989,
Pubmed
Attenburrow,
Melatonin phase advances circadian rhythm.
1995,
Pubmed
Bittman,
The distribution of melatonin binding sites in neuroendocrine tissues of the ewe.
1990,
Pubmed
Blazynski,
Localization of 2-[125I]iodomelatonin binding sites in mammalian retina.
1991,
Pubmed
Bradford,
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
1976,
Pubmed
Daniolos,
Action of light on frog pigment cells in culture.
1990,
Pubmed
,
Xenbase
Dollins,
Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance.
1994,
Pubmed
Dubocovich,
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.
1997,
Pubmed
Dubocovich,
Luzindole (N-0774): a novel melatonin receptor antagonist.
1988,
Pubmed
Dubocovich,
Melatonin receptors: are there multiple subtypes?
1995,
Pubmed
Ebisawa,
Expression cloning of a high-affinity melatonin receptor from Xenopus dermal melanophores.
1994,
Pubmed
,
Xenbase
Garratt,
Mapping the melatonin receptor. 3. Design and synthesis of melatonin agonists and antagonists derived from 2-phenyltryptamines.
1995,
Pubmed
,
Xenbase
Geary,
Melatonin directly constricts rat cerebral arteries through modulation of potassium channels.
1997,
Pubmed
Harper,
Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2'0 acetylation by acetic anhydride in aqueous solution.
1975,
Pubmed
Hill,
Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF-7) in culture.
1988,
Pubmed
Holmes,
Effects of melatonin on sleep and neurochemistry in the rat.
1982,
Pubmed
Kenakin,
Effects of in vivo beta-adrenoceptor down-regulation on cardiac responses to prenalterol and pirbuterol.
1983,
Pubmed
Kenakin,
The relative contribution of affinity and efficacy to agonist activity: organ selectivity of noradrenaline and oxymetazoline with reference to the classification of drug receptors.
1984,
Pubmed
Kenakin,
The classification of drugs and drug receptors in isolated tissues.
1984,
Pubmed
Mazzucchelli,
The melatonin receptor in the human brain: cloning experiments and distribution studies.
1996,
Pubmed
McClintock,
Melanophore pigment dispersion responses to agonists show two patterns of sensitivity to inhibitors of cAMP-dependent protein kinase and protein kinase C.
1996,
Pubmed
,
Xenbase
Morgan,
Melatonin receptors: localization, molecular pharmacology and physiological significance.
1994,
Pubmed
Morrey,
Activation of human monocytes by the pineal hormone melatonin.
1994,
Pubmed
Pappolla,
Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide.
1997,
Pubmed
Pickering,
Analogues of diverse structure are unable to differentiate native melatonin receptors in the chicken retina, sheep pars tuberalis and Xenopus melanophores.
1996,
Pubmed
,
Xenbase
Potenza,
A rapid quantitative bioassay for evaluating the effects of ligands upon receptors that modulate cAMP levels in a melanophore cell line.
1992,
Pubmed
,
Xenbase
Reiter,
A review of the evidence supporting melatonin's role as an antioxidant.
1995,
Pubmed
Reppert,
Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor.
1995,
Pubmed
Reppert,
Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses.
1994,
Pubmed
,
Xenbase
Reppert,
Melatonin receptors are for the birds: molecular analysis of two receptor subtypes differentially expressed in chick brain.
1995,
Pubmed
,
Xenbase
Sugden,
Melatonin receptor pharmacology: toward subtype specificity.
1997,
Pubmed
,
Xenbase
Ting,
Studies on the vasoconstrictor action of melatonin and putative melatonin receptor ligands in the tail artery of juvenile Wistar rats.
1997,
Pubmed
Vanecek,
Atypical synergistic alpha 1- and beta-adrenergic regulation of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in rat pinealocytes.
1985,
Pubmed
White,
Pertussis toxin blocks melatonin-induced pigment aggregation in Xenopus dermal melanophores.
1987,
Pubmed
,
Xenbase