The A₃ adenosine receptor mediates cell spreading, reorganization of actin cytoskeleton, and distribution of Bcl-x(L): Studies in human astroglioma cells

The pathophysiological role of the adenosine A₃ receptor in the central nervous system is largely unknown. We have investigated the effects of the selective A₃ receptor agonist 2-chloro-N⁶-(3-iodobenzyl)-adenosine, CI-IB-MECA, in cells of the astroglial lineage (human astrocytoma ADF cells). A marked reorganization of the cytoskeleton, with appearance of stress fibers and numerous cell protrusions, was found following exposure of cells to low (nM) concentrations of CI-IB-MECA. These 'trophic' effects were accompanied by induction of the expression of Rho, a small GTP-binding protein, which was virtually absent in control cells, and by changes of the intracellular distribution of the antiapoptotic protein Bcl-x(L), that, in agonist-exposed cells, became specifically associated to cell protrusions. This is the first demonstration that the intracellular organization of Bcl-x(L) can be modulated by the activation of a G-protein-coupled membrane receptor, such as the A₃ adenosine receptor. Moreover, modulation of the astrocytic cytoskeleton by adenosine may have intriguing implications in both nervous system development and in the response of the brain to trauma and ischemia.