title: Modulation of pineal melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through NF-κB activation.
abstract: The glutamatergic modulation of melatonin synthesis is well known, along with the importance of astrocytes in mediating glutamatergic signaling in the central nervous system. Pinealocytes and astrocytes are the main cell types in the pineal gland. The objective of this work was to investigate the interactions between astrocytes and pinealocytes as a part of the glutamate inhibitory effect on melatonin synthesis. Rat pinealocytes isolated or in coculture with astrocytes were incubated with glutamate in the presence of norepinephrine, and the melatonin content, was quantified. The expression of glutamate receptors, the intracellular calcium content and the NF- κ B activation were analyzed in astrocytes and pinealocytes. TNF- α 's possible mediation of the effect of glutamate was also investigated. The results showed that glutamate's inhibitory effect on melatonin synthesis involves interactions between astrocytes and pinealocytes, possibly through the release of TNF- α . Moreover, the activation of the astrocytic NF- κ B seems to be a necessary step. In astrocytes and pinealocytes, AMPA, NMDA, and group I metabotropic glutamate receptors were observed, as well as the intracellular calcium elevation. In conclusion, there is evidence that the modulation of melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through the activation of the astrocytic NF- κ B transcription factor and possibly by subsequent TNF- α release.
authors.affiliation: Laboratory of Pharmacology, Butantan Institute, Avenida Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil.
authors.forename: Darine
authors.initials: D
authors.lastname: Villela
authors.forename: Victoria Fairbanks
authors.initials: VF
authors.lastname: Atherino
authors.forename: Larissa de Sá
authors.initials: Lde S
authors.lastname: Lima
authors.forename: Anderson Augusto
authors.initials: AA
authors.lastname: Moutinho
authors.forename: Fernanda Gaspar
authors.initials: FG
authors.lastname: do Amaral
authors.forename: Rafael
authors.initials: R
authors.lastname: Peres
authors.forename: Thais
authors.initials: T
authors.lastname: Martins de Lima
authors.forename: Andréa da Silva
authors.initials: Ada S
authors.lastname: Torrão
authors.forename: José
authors.initials: J
authors.lastname: Cipolla-Neto
authors.forename: Cristóforo
authors.initials: C
authors.lastname: Scavone
authors.forename: Solange Castro
authors.initials: SC
authors.lastname: Afeche
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D019899:Paracrine Communication / Q000187:drug effects*; D010870:Pineal Gland / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; D017470:Receptors, Glutamate; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D018698:Glutamic Acid; D011392:Proline; D008550:Melatonin; D002118:Calcium