title: Microglia express GABA(B) receptors to modulate interleukin release.
abstract: gamma-Aminobutyric acid (GABA) can act as a neuroprotective agent besides its well-established role as the main inhibitory neurotransmitter in the CNS. Here we report that microglial cells express GABA(B) receptors indicating that these prominent immunocompetent cells in the brain are a target for GABA. Agonists of GABA(B) receptors triggered the induction of K(+) conductance in microglial cells from acute brain slices and in culture. Both subunits of GABA(B) receptors were identified in cultured microglia by Western blot analysis and immunocytochemistry, and were detected on a subpopulation of microglia in situ by immunohistochemistry. In response to facial nerve axotomy, we observed an increase in GABA(B) receptor expressing microglial cells in the facial nucleus. We activated microglial cells in culture with lipopolysaccharide (LPS) to induce the release of interleukin-6 and interleukin-12p40. This release activity was attenuated by simultaneous activation of the GABA(B) receptors indicating that GABA can modulate the microglial immune response.
authors.affiliation: Department of Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine, D-13125 Berlin, Germany.
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Kuhn
authors.forename: Frank K H
authors.initials: FK
authors.lastname: van Landeghem
authors.forename: Robert
authors.initials: R
authors.lastname: Zacharias
authors.forename: Katrin
authors.initials: K
authors.lastname: Färber
authors.forename: Angelika
authors.initials: A
authors.lastname: Rappert
authors.forename: Sanja
authors.initials: S
authors.lastname: Pavlovic
authors.forename: Anja
authors.initials: A
authors.lastname: Hoffmann
authors.forename: Christiane
authors.initials: C
authors.lastname: Nolte
authors.forename: Helmut
authors.initials: H
authors.lastname: Kettenmann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019771:Axotomy; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020220:Facial Nerve Injuries / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D005911:Gliosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; D015221:Potassium Channels; D021122:Protein Subunits; D018080:Receptors, GABA-B; D018664:Interleukin-12; D005680:gamma-Aminobutyric Acid