Endogenous purinergic signaling is required for osmotic volume regulation of retinal glial cells.
Intense neuronal activity in the sensory retina is associated with a volume increase of neuronal cells (Uckermann et al., J. Neurosci. 2004, 24:10149) and a decrease in the osmolarity of the extracellular space fluid (Dmitriev et al., Vis. Neurosci. 1999, 16:1157). Here, we show the existence of an endogenous purinergic mechanism that prevents hypoosmotic swelling of retinal glial (Müller) cells in mice. In contrast to the cells from wild-type mice, hypoosmotic stress induced rapid swelling of glial cell somata in retinal slices from mice deficient in P2Y(1), adenosine A(1) receptors, or ecto-5'-nucleotidase (CD73). Consistently, glial cell bodies in retinal slices from wild-type mice displayed osmotic swelling when P2Y(1) or A(1) receptors, or CD73, were pharmacologically blocked. Exogenous ATP, UTP, and UDP inhibited glial swelling in retinal slices, while the swelling of isolated glial cells was prevented by ATP but not by UTP or UDP, suggesting that uracil nucleotides indirectly regulate the glial cell volume via activation of neuronal P2Y(4/6) and neuron-to-glia signaling. It is suggested that autocrine/paracrine activation of purinergic receptors and enzymes is crucially involved in the regulation of the glial cell volume.
Wurm
Antje
A
Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
Lipp
Stephan
S
Pannicke
Thomas
T
Linnertz
Regina
R
Krügel
Ute
U
Schulz
Angela
A
Färber
Katrin
K
Zahn
Dirk
D
Grosse
Johannes
J
Wiedemann
Peter
P
Chen
Ju
J
Schöneberg
Torsten
T
Illes
Peter
P
Reichenbach
Andreas
A
Bringmann
Andreas
A
D015720:5'-Nucleotidase / Q000172:deficiency; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017609:Barium Compounds / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D009995:Osmosis; D026902:Potassium Channel Blockers / Q000494:pharmacology; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D011742:Pyrimidine Nucleotides / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000172:deficiency / Q000378:metabolism*; D012160:Retina / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D014631:Valerates / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
C528918:2,2-dimethylpropionic acid 3-(2-chloro-6-methylaminopurin-9-yl)-2-(2,2-dimethylpropionyloxymethyl)propyl ester; D017609:Barium Compounds; D002712:Chlorides; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D026902:Potassium Channel Blockers; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D011742:Pyrimidine Nucleotides; D000644:Quaternary Ammonium Compounds; D011983:Receptors, Purinergic; D013873:Thionucleotides; D014631:Valerates; D014970:Xanthines; C024986:barium chloride; C018444:adenosine 5'-O-(1-thiodiphosphate); D000244:Adenosine Diphosphate; C022799:clofilium; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000242:Cyclic AMP; D015720:5'-Nucleotidase; D000225:Adenine; D002118:Calcium