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Involvement of P2 purinoceptors in the regulation ofdna synthesis in the neural retina of chick embryo
Author(s) -
Sugioka Miho,
Zhou Wenliang,
Hofmann Hansdieter,
Yamashita Masayuki
Publication year - 1999
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/s0736-5748(98)00066-5
Subject(s) - ppads , suramin , biology , retina , purinergic receptor , microbiology and biotechnology , retinal , extracellular , retinal pigment epithelium , muller glia , biochemistry , in vitro , neuroscience , progenitor cell , stem cell
The activation of P2 purinoceptors induces Ca 2 mobilization in the earlyembryonic chick neural retina. This purinergic Ca 2 response declines parallel with thedecrease in mitotic activity during retinal development. To investigate the role of P2purinoceptors in the regulation of retinal cell proliferation, we studied the effects of the P2purinoceptor antagonists suramin and pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS), and of the agonist ATP on DNA synthesis in retinal organcultures from embryonic day 3 (E3) chick. Suramin inhibited [ 3 H]‐thymidineincorporation in a dose‐dependent manner (IC 50 : ∼70 μ M). PPADS alsoreduced [ 3 H]‐thymidine incorporation with maximum inhibition of 46% at 100 μ M. Exogenous ATP enhanced [ 3 H]‐thymidine incorporation in adose‐dependent manner to maximally 200% of control (EC 50 : ∼70 μ M). Indissociated retinal cultures from E7 chick, both antagonists showed similar inhibitory effects on [ 3 H]‐thymidine incorporation without affecting cell viability. In line with theseobservations, the presence of extracellular ATP was demonstrated both in vitro and in vivo . In the medium of E3 retinal organ cultures, the concentration of ATP increased25‐fold within 1 h of incubation and this concentration was kept for at least 24 h. In the chickamniotic fluid, the ATP concentration was nearly 3 μ M at E3 and declined to 0.15 μ M at E7. The results indicate that P2 purinoceptors activated by autocrine or paracrinerelease of ATP are involved in the regulation of DNA synthesis in the neural retina at earlyembryonic stages.