P2 receptors on macroglial cells: Functional implications for gliosis

The present review summarizes data about the expression of P2 receptors in two types of macroglial cells, i.e., in astrocytes of the nucleus accumbens (NAc) and Moller glial cells of the retina. Changes in the expression of t hese receptors during pathological conditions may indicate an involvement i n the induction and/or maintenance of reactive astrogliosis. In fact, astro cytic proliferation was induced in the NAc by the application of different P2X and P2Y receptor agonists, such as 2-methylthio ATP (2-MeSATP), alpha,b eta -methylene adenosine 5'-triphosphate (alpha,beta -meATP) and adenosine 5'-O-(2-thiodiphosphate (ADP-beta -S). An increased content of glial fibril lary acidic protein, astrocytic hypertrophy, and proliferation as indicated by enhanced incorporation of 5-bromo-2'-deoxyuridine (BrdU) was found unde r these conditions; an enhanced BrdU incorporation signalizes a higher rate of DNA synthesis. Moller glial cells of the human retina express both meta botropic P2Y and ionotropic P2X(7) receptors. Application of the P2X(7) rec eptor agonist benzoyl-benzoyl ATP (BzATP) evoked a cationic conductance inc rease that led to the depolarization of cells and to Ca2+ entry from the ex tracellular space. Long-lasting application of BzATP, however, did not caus e the formation of pores permeable for large molecules, excluding the prese nce of classic P2X(7) receptors. Moller glial cells of the human retina sho w increased P2X(7) receptor-mediated cationic currents during proliferative gliosis. A role of P2X(7) receptors in glial proliferation is also indicat ed by the observation that the DNA synthesis rate of cultured Moller cells is enhanced in the presence of BzATP, as shown by the measurement of BrdU i ncorporation. The data indicate that activation of P2 receptors may exert b oth short- and long-term effects in macroglial cells, and that these recept ors may be involved in glial responses to pathological conditions. (C) 2001 Wiley-Liss, Inc.