Involvement of P2 purinoceptors in the regulation of DNA synthesis in the neural retina of chick embryo

The activation of P2 purinoceptorS induces Ca2+ mobilization in the early e mbryonic chick neural retina. This purinergic Ca2+ response declines parall el with the decrease in mitotic activity retinal development. To investigat e the role of P2 purinoceptors in the regulation of retinal cell proliferat ion. we studied the effects of the P2 purinoceptor antagonists suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), and of the a gonist ATP on DNA synthesis in retinal organ cultures from embryonic day 3 (E3) chick. Suramin inhibited [H-3]-thymidine incorporation in a dose-depen dent manner (IC50: similar to 70 mu M). PPADS also reduced [H-3]-thymidine incorporation with maximum inhibition of 46% at 100 mu M. Exogenous ATP enh anced [H-3]-thymidine incorporation in a dose-dependent manner to maximally 200% of control (EC50: similar to 70 mu M). In dissociated retinal culture s from E7 chick, both antagonists showed similar inhibitory effects on [H-3 ]-thymidine incorporation without affecting cell viability. In line with th ese observations, the presence of extracellular ATP was demonstrated both i n vitro and in vivo. In the medium of E3 retinal organ cultures, the concen tration of ATP increased 25-fold within 1 h of incubation and this concentr ation was kept for at least 24 h. In the chick amniotic fluid, the ATP conc entration was nearly 3 mu M at E3 and declined to 0.15 mu M at E7. The resu lts indicate that P2 purinoceptors activated by autocrine or paracrine rele ase of ATP are involved in the regulation of DNA synthesis in the neural re tina at early embryonic stages. (C) 1999 ISDN. Published by Elsevier Scienc e Ltd. All rights reserved.