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 these receptors during pathological conditions may indicate an involvement in the induction and/or maintenance of reactive astrogliosis. In fact, astrocytic proliferation was induced in the NAc by the application of different P2X and P2Y receptor agonists, such as 2-methylthio ATP (2-MeSATP), alpha,beta -methylene adenosine 5'-triphosphate (alpha,beta -meATP) and adenosine 5'-O-(2-thiodiphosphate (ADP-beta -S). An increased content of glial fibrillary acidic protein, astrocytic hypertrophy, and proliferation as indicated by enhanced incorporation of 5-bromo-2'-deoxyuridine (BrdU) was found under these conditions; an enhanced BrdU incorporation signalizes a higher rate of DNA synthesis. Moller glial cells of the human retina express both metabotropic P2Y and ionotropic P2X(7) receptors. Application of the P2X(7) receptor agonist benzoyl-benzoyl ATP (BzATP) evoked a cationic conductance increase that led to the depolarization of cells and to Ca2+ entry from the extracellular space. Long-lasting application of BzATP, however, did not cause the formation of pores permeable for large molecules, excluding the presence of classic P2X(7) receptors. Moller glial cells of the human retina show increased P2X(7) receptor-mediated cationic currents during proliferative gliosis. A role of P2X(7) receptors in glial proliferation is also indicated 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 incorporation. The data indicate that activation of P2 receptors may exert both short- and long-term effects in macroglial cells, and that these receptors may be involved in glial responses to pathological conditions. (C) 2001 Wiley-Liss, Inc.