title: Endogenous purinergic signaling is required for osmotic volume regulation of retinal glial cells.
abstract: 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.
authors.affiliation: Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Wurm
authors.forename: Stephan
authors.initials: S
authors.lastname: Lipp
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.forename: Regina
authors.initials: R
authors.lastname: Linnertz
authors.forename: Ute
authors.initials: U
authors.lastname: Krügel
authors.forename: Angela
authors.initials: A
authors.lastname: Schulz
authors.forename: Katrin
authors.initials: K
authors.lastname: Färber
authors.forename: Dirk
authors.initials: D
authors.lastname: Zahn
authors.forename: Johannes
authors.initials: J
authors.lastname: Grosse
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
authors.forename: Torsten
authors.initials: T
authors.lastname: Schöneberg
authors.forename: Peter
authors.initials: P
authors.lastname: Illes
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.forename: Andreas
authors.initials: A
authors.lastname: Bringmann
mesh_terms: 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
chemical_list: 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