P2 receptor-types involved in astrogliosis in vivo

1 In the nucleus accumbens (NAc) of rats, the involvement of P2X and P2Y re ceptors in the generation of astrogliosis in vivo, was investigated by loca l application of their respective ligands. The agonists used had selectivit ies for P2X(1.3) (alpha,beta -methylene adenosine 5'-triphosphate; alpha,be ta -meATP),P2Y(1,12) (adenosine 5'-O-(2-thiodiphosphate, ADP-beta -S) and P 2Y(2,4,6) receptors (uridine 5'-O-(3-thiotriphosphate; UTP-gamma -S). Pyrid oxalphosphate-6-azophenyl-2,4-disulphonic acid (PPADS) was used as a non-se lective antagonist. The astroglial reaction was studied by means of immunoc ytochemical double-labelling with antibodies to glial fibrillary acidic pro tein (GFAP) and 5-bromo-2'-deoxyuridine (BrdU). 2 The agonist-induced changes in comparison to the artificial cerebrospinal fluid (aCSF)-treated control side reveal a strong mitogenic potency of ADP -beta -S and alpha,beta -meATP, whereas UTP-gamma -S was ineffective. The P 2 receptor antagonist PPADS decreased the injury-induced proliferation when given alone and in addition inhibited all agonist effects. 3 The observed morphogenic changes included hypertrophy of astrocytes, elon gation of astrocytic processes and up-regulation of GFAP. A significant inc rease of both GFAP-immunoreactivity (IR) and GFA-protein content (by using Western blotting) was found after microinfusion of alpha,beta -meATP or ADP -beta -S. In contrast, UTP-gamma -S failed to increase the GFAP-IR. The mor phogenic effects were also inhibited by pre-treatment with PPADS. 4 A double immunofluorescence approach with confocal laser scanning microsc opy showed the localisation of P2X(3) and P2Y(1) receptors on the GFAP- lab elled astrocytes. 5 In conclusion, the data suggest that P2Y (P2Y(1) or P2Y(12)) receptor sub types are involved in the generation of astrogliosis in the NAc of rats, wi th a possible minor contribution of P2X receptor subtypes.