P2 purinoceptor expression and functional changes of hypoxia-activated cultured rat retinal microglia

P2 purinoceptors appear to modulate microglia function, but their role in h ypoxic microglia has not been investigated. We examined in postnatal rat re tinal microglia cultured under hypoxic (1% oxygen) condition, their P2 expr ession, proliferation and cytokine release in the presence or absence of th e P2 receptor agonists and antagonists. Fura-2 fluorescence measurements of intracellular Ca2+ rises to P2 receptor agonists and antagonists indicated that both P-2U and P-2Z were expressed in hypoxic microglia. Hypoxia induc ed BrdU incorporation and release of interleukin-1 beta (IL-1 beta) and tum or necrosis factor-alpha (TNF-alpha) as well. The P-2U agonist, UTP, mainta ined the BrdU incorporation, whereas the P2Z agonist, BzATP, suppressed it, but significantly enhanced IL-1 beta and TNF-alpha release, suggesting tha t the P-2U response may underlie the mitotic activity, a nd that of P-2Z, t he IL-1 beta and TNF-alpha release of hypoxia-activated microglia. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.