title: Synergistic action of hypoosmolarity and glutamine in inducing acute swelling of retinal glial (Müller) cells.
abstract: High blood ammonia, elevated glutamine, and hyponatremia are pathogenic factors contributing to astrocytic swelling and brain edema in liver failure. We investigated the effects of hypoosmolarity, ammonia, and glutamine on the induction of glial cell swelling in freshly isolated slices of the rat retina. Glutamine, but not ammonia or hypoosmolarity per se, evoked a rapid (within one minute) swelling of retinal glial (Müller) cell bodies under hypoosmotic conditions. Under isoosmotic conditions, glutamine evoked a delayed swelling after 10 min of exposure. The effect of glutamine was concentration-dependent, with half-maximal and maximal effects at ∼ 0.1 and 0.5 mM. Glutamine in hypoosmotic solution induced a dissipation of the mitochondrial membrane potential. The effects on the mitochondrial membrane potential and the glial soma size were reduced by (i) agents which inhibit the transfer of glutamine into mitochondria and its hydrolysis there, (ii) inhibition of the mitochondrial permeability transition, (iii) inhibitors of oxidative-nitrosative stress, and (iv) inhibitors of phospholipase A(2) and cyclooxygenase. Glutamine-induced glial swelling was also prevented by ATP and adenosine, acting at adenosine A(1) receptors. The data suggest that hypoosmolarity accelerates the swelling-inducing effect of glutamine on retinal glial cells, and that swelling induction by glutamine is mediated by inducing oxidative-nitrosative stress, inflammatory lipid mediators, and mitochondrial dysfunction.
authors.affiliation: Department Pathophysiology of Neuroglia, Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Anett
authors.initials: A
authors.lastname: Karl
authors.forename: Antje
authors.initials: A
authors.lastname: Wurm
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.forename: Katja
authors.initials: K
authors.lastname: Krügel
authors.forename: Marta
authors.initials: M
authors.lastname: Obara-Michlewska
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.forename: Jan
authors.initials: J
authors.lastname: Albrecht
authors.forename: Andreas
authors.initials: A
authors.lastname: Bringmann
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects*; D003980:Diazooxonorleucine / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005973:Glutamine / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects*; D009995:Osmosis / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D004791:Enzyme Inhibitors; D014970:Xanthines; D003980:Diazooxonorleucine; D005973:Glutamine; D016718:Arachidonic Acid; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D006861:Hydrogen Peroxide; D000241:Adenosine; D015232:Dinoprostone