title: Activation of mouse microglial cells affects P2 receptor signaling.
abstract: Microglial cells are the immunocompetent cells of the CNS, which are known to exist in several activation states. Here we investigated the impact of microglial activation on the P2 receptor-mediated intracellular calcium ([Ca(2+)](i)) signaling by means of fluo-3 based Ca(2+)-imaging. Cultured mouse microglial cells were treated with either astrocyte-conditioned medium to induce a ramified morphology or LPS to shift the cells toward the fully activated stage. The extracellular application of ATP (100 microM) induced a [Ca(2+)](i) elevation in 85% of both untreated and ramified microglial cells, whereas only 50% of the LPS-activated cells responded to the stimulus. To characterise the pharmacological profile of microglial P2 receptors we investigated the effects of various P2 agonists on [Ca(2+)](i) in cultured microglial cells. Untreated and ramified microglial cells demonstrated a very similar sensitivity to the different P2 agonists. In contrast, in LPS-activated microglia, a sharp decrease of responses to P2 agonist stimulation was seen. This indicates that microglial activation influences the capability of microglial cells to generate [Ca(2+)](i) signals upon P2 receptor activation.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13122, Berlin-Buch, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Möller
authors.forename: O
authors.initials: O
authors.lastname: Kann
authors.forename: A
authors.initials: A
authors.lastname: Verkhratsky
authors.forename: H
authors.initials: H
authors.lastname: Kettenmann
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000814:Aniline Compounds; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D003337:Corpus Callosum; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D008070:Lipopolysaccharides; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D014966:Xanthenes; C059715:Fluo-3; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium