title: Glutamate release by neurons evokes a purinergic inhibitory mechanism of osmotic glial cell swelling in the rat retina: activation by neuropeptide Y.
abstract: Glial cell swelling is a central cause of ischemic edema in the brain and retina; however, the regulation of glial cell volume by endogenous factors in situ is largely unknown. In slices of the postischemic retina of the rat, the somata of glial (Müller) cells swell upon hypotonic stress that is not observed in slices of control retinas. We describe an endogenous signaling pathway that leads to inhibition of the osmotic glial cell swelling, and that is evoked by the release of glutamate from retinal neurons upon application of neuropeptide Y. Glutamate activates metabotropic glutamate receptors on swollen glial cells, which evokes a Ca2+ -independent purinergic signaling cascade that involves release of ATP, P2Y1 receptor activation, and transporter-mediated release of adenosine. Activation of A1 receptors causes the inhibition of osmotic glial cell swelling, by a protein kinase A-dependent activation of K+ and Cl- channels. It is proposed that the glutamate-evoked purinergic receptor signaling of glial cells is crucially involved in the cell volume homeostasis of the retina, and that this mechanism may contribute to the protective effect of adenosine in the ischemic tissue.
authors.affiliation: Paul Flechsig Institute of Brain Research, Medical Faculty of the University of Leipzig, Leipzig, Germany.
authors.forename: Ortrud
authors.initials: O
authors.lastname: Uckermann
authors.forename: Antje
authors.initials: A
authors.lastname: Wolf
authors.forename: Franziska
authors.initials: F
authors.lastname: Kutzera
authors.forename: Folke
authors.initials: F
authors.lastname: Kalisch
authors.forename: Annette G
authors.initials: AG
authors.lastname: Beck-Sickinger
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.forename: Andreas
authors.initials: A
authors.lastname: Bringmann
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D003627:Data Interpretation, Statistical; D018698:Glutamic Acid / Q000378:metabolism*; D007511:Ischemia / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000648:ultrastructure*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017470:Receptors, Glutamate / Q000187:drug effects; D011983:Receptors, Purinergic / Q000187:drug effects*; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure*; D012171:Retinal Vessels / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D009478:Neuropeptide Y; D017470:Receptors, Glutamate; D011983:Receptors, Purinergic; D018698:Glutamic Acid; D002118:Calcium