Activation of mouse microglial cells affects P2 receptor signaling

Microglial cells are the immunocompetent cells of the CNS, which are known to exist in several activation states. Here we investigated the impact of m icroglial activation on the P2 receptor-mediated intracellular calcium ([Ca 2+]ii) signaling by means of fluo-3 based Ca2+-imaging. Cultured mouse micr oglial cells were treated with either astrocyte-conditioned medium to induc e a ramified morphology or LPS to shift the cells toward the fully activate d stage. The extracellular application of ATP (100 mu M) induced a [Ca2+], elevation in 85% of both untreated and ramified microglial cells, whereas o nly 50% of the LPS-activated cells responded to the stimulus. To characteri se the pharmacological profile of microglial P2 receptors we investigated t he effects of various P2 agonists on [Ca2+](i) in cultured microglial cells . Untreated and ramified microglial cells demonstrated a very similar sensi tivity to the different P2 agonists. In contrast, in LPS-activated microgli a, a sharp decrease of responses to P2 agonist stimulation was seen. This i ndicates that microglial activation influences the capability of microglial cells to generate [Ca2+]i signals upon P2 receptor activation. (C) 2000 El sevier Science B.V. All rights reserved.