Melatonin desensitizes endogenous MT 2 melatonin receptors in the rat suprachiasmatic nucleus: relevance for defining the periods of sensitivity of the mammalian circadian clock to melatonin
| Autor: | Monica I. Masana, Moisés A. Rivera-Bermúdez, Margarita L. Dubocovich, Randall L. Hudson, David J. Earnest, Martha U. Gillette, Matthew J. Gerdin |
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| Rok vydání: | 2004 |
| Předmět: |
endocrine system
medicine.medical_specialty Circadian clock Down-Regulation Biology Biochemistry Melatonin receptor Cell Line Pinealocyte Melatonin Cricetinae Internal medicine Genetics medicine Animals Humans Circadian rhythm Receptor Molecular Biology Neurons Receptor Melatonin MT2 Suprachiasmatic nucleus Brain Circadian Rhythm Rats Protein Transport Endocrinology Light effects on circadian rhythm Suprachiasmatic Nucleus hormones hormone substitutes and hormone antagonists Biotechnology medicine.drug |
| Zdroj: | The FASEB Journal. 18:1646-1656 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.03-1339com |
| Popis: | The hormone melatonin phase shifts circadian rhythms generated by the mammalian biological clock, the suprachiasmatic nucleus (SCN) of the hypothalamus, through activation of G protein-coupled MT2 melatonin receptors. This study demonstrated that pretreatment with physiological concentrations of melatonin (30-300 pM or 7-70 pg/mL) decreased the number of hMT2 melatonin receptors heterologously expressed in mammalian cells in a time and concentration-dependent manner. Furthermore, hMT2-GFP melatonin receptors heterologously expressed in immortalized SCN2.2 cells or in non-neuronal mammalian cells were internalized upon pretreatment with both physiological (300 pM or 70 pg/mL) and supraphysiological (10 nM or 2.3 ng/mL) concentrations of melatonin. The decrease in MT2 melatonin receptor number induced by melatonin (300 pM for 1 h) was reversible and reached almost full recovery after 8 h; however, after treatment with 10 nM melatonin full recovery was not attained even after 24 h. This recovery process was partially protein synthesis dependent. Furthermore, exposure to physiological concentrations of melatonin (300 pM) for a time mimicking the nocturnal surge (8 h) desensitized functional responses mediated through melatonin activation of endogenous MT2 receptors, i.e., stimulation of protein kinase C (PKC) in immortalized SCN2.2 cells and phase shifts of circadian rhythms of neuronal firing in the rat SCN brain slice. We conclude that in vivo the nightly secretion of melatonin desensitizes endogenous MT2 melatonin receptors in the mammalian SCN thereby providing a temporally integrated profile of sensitivity of the mammalian biological clock to a melatonin signal. |
| Databáze: | OpenAIRE |
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