THE A(3) 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 As receptor in the centra l nervous system is largely unknown. We have investigated the effects of the selective A(3) receptor agonist 2-chloro-N-6-(3-iodobenzyl)-ade nosine, Cl-IB-MECA, in cells of the astroglial lineage (human astrocyt oma ADF cells). A marked reorganization of the cytoskeleton, with appe arance of stress fibers and numerous cell protrusions, was found follo wing exposure of cells to low (nM) concentrations of Cl-IB-MECA. These ''trophic'' effects were accompanied by induction of the expression o f Rho, a small GTP-binding protein, which was virtually absent in cont rol cells, and by changes of the intracellular distribution of the ant iapoptotic protein Bcl-x(L), that, in agonist-exposed cells, became sp ecifically associated to cell protrusions. This is the first demonstra tion that the intracellular organization of Bcl-x(L) can be modulated by the activation of a G-protein coupled membrane receptor, such as th e A(3) adenosine receptor. Moreover, modulation of the astrocytic cyto skeleton by adenosine may have intriguing implications in both nervous system development and in the response of the brain to trauma and isc hemia. (C) 1997 Academic Press.