Afobazole Modulates Microglial Function via Activation of Both σ-1 and σ-2 Receptors

• DOI: 10.1124/jpet.111.182816
• Publication Date: 2011-06-30T02:18:27Z
• Authors: Javier Cuevas; Alex Rodriguez; Adam Behensky; Chris Katnik
• Keywords: Cytoprotection

Microglial cells play a critical role in the neuroinflammatory response that accompanies various diseases of central nervous system, such as ischemic stroke, and ATP is major signaling molecule regulating these to pathophysiological conditions. Experiments were carried out determine effects afobazole on microglial function identify molecular mechanisms by which affects cells. Afobazole was found inhibit migration UTP chemoattraction concentration-dependent manner. Inhibition either σ-1 or σ-2 receptors decreased microglia. In addition inhibiting cell migration, activation σ intracellular calcium elevation produced focal application isolated Furthermore, blocked membrane currents elicited rapid Taken together, our data indicate inhibits P2Y P2X purinergic receptor functioning pan-selective σ-receptor agonist. modulating activation, survival during vitro ischemia assessed. Application death episode after 24-h recovery period. Moreover, when only applied episode, significant enhancement still observed. Thus, acts via decrease provides cytoprotection ischemia.