Sigma-1 receptor activation inhibits osmotic swelling of rat retinal glial (Müller) cells by transactivation of glutamatergic and purinergic receptors.
Water accumulation in retinal glial (Müller) and neuronal cells resulting in cellular swelling contributes to the development of retinal edema and neurodegeneration. Sigma (σ) receptor activation is known to have neuroprotective effects in the retina. Here, we show that the nonselective σ receptor agonist ditolylguanidine, and the selective σ1 receptor agonist PRE-084, inhibit the osmotic swelling of Müller cell somata induced by superfusion of rat retinal slices with a hypoosmotic solution containing barium ions. In contrast, PRE-084 did not inhibit the osmotic swelling of bipolar cell somata. The effects of σ receptor agonists on the Müller cell swelling were abrogated in the presence of blockers of metabotropic glutamate and purinergic P2Y1 receptors, respectively, suggesting that σ receptor activation triggers activation of a glutamatergic-purinergic signaling cascade which is known to prevent the osmotic Müller cell swelling. The swelling-inhibitory effect of 17β-estradiol was prevented by the σ1 receptor antagonist BD1047, suggesting that the effect is mediated by σ1 receptor activation. The data may suggest that the neuroprotective effect of σ receptor activation in the retina is in part mediated by prevention of the cytotoxic swelling of retinal glial cells.
Paul Flechsig Institute of Brain Research, University of Leipzig, 04103 Leipzig, Germany.
Stefanie
S
Vogler
Paul Flechsig Institute of Brain Research, University of Leipzig, 04103 Leipzig, Germany.
Helge
H
Winters
Paul Flechsig Institute of Brain Research, University of Leipzig, 04103 Leipzig, Germany.
Thomas
T
Pannicke
Department of Ophthalmology and Eye Hospital, University of Leipzig, 04103 Leipzig, Germany.
Peter
P
Wiedemann
Paul Flechsig Institute of Brain Research, University of Leipzig, 04103 Leipzig, Germany.
Andreas
A
Reichenbach
Department of Ophthalmology and Eye Hospital, University of Leipzig, 04103 Leipzig, Germany. Electronic address: bria@medizin.uni-leipzig.de.
Andreas
A
Bringmann
D000818:Animals; D048429:Cell Size; D063928:Ependymoglial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009995:Osmosis; D058919:Purinergic P2 Receptor Antagonists / Q000494:pharmacology; D020318:Rats, Long-Evans; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics / Q000378:metabolism*; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015533:Transcriptional Activation
D005029:Ethylenediamines; D018691:Excitatory Amino Acid Antagonists; D009025:Morpholines; D058919:Purinergic P2 Receptor Antagonists; D017470:Receptors, Glutamate; D058472:Receptors, Purinergic P2Y1; D017480:Receptors, sigma; C071738:2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; D004958:Estradiol
Bipolar cell; Cell swelling; Estradiol; Müller cell; Retina; Sigma receptor