P2 Purinoceptor expression and functional changes of hypoxia-activated cultured rat retinal microglia.
P(2) purinoceptors appear to modulate microglia function, but their role in hypoxic microglia has not been investigated. We examined in postnatal rat retinal microglia cultured under hypoxic (1% oxygen) condition, their P2 expression, proliferation and cytokine release in the presence or absence of the P2 receptor agonists and antagonists. Fura-2 fluorescence measurements of intracellular Ca(2+) rises to P2 receptor agonists and antagonists indicated that both P(2U) and P(2Z) were expressed in hypoxic microglia. Hypoxia induced BrdU incorporation and release of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as well. The P(2U) agonist, UTP, maintained the BrdU incorporation, whereas the P(2Z) agonist, BzATP, suppressed it, but significantly enhanced IL-1beta and TNF-alpha release, suggesting that the P(2U) response may underlie the mitotic activity, and that of P(2Z), the IL-1beta and TNF-alpha release of hypoxia-activated microglia.
Morigiwa
K
K
Department of Physiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. km@phys2.med.osaka-u.ac.jp
Quan
M
M
Murakami
M
M
Yamashita
M
M
Fukuda
Y
Y
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D015687:Cell Hypoxia; D002478:Cells, Cultured; D007375:Interleukin-1 / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D058473:Receptors, Purinergic P2Y2; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; C546470:P2rx7 protein, rat; C546387:P2ry2 protein, rat; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D058473:Receptors, Purinergic P2Y2; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium