Effect of SA4503, a novel σ1 receptor agonist, against glutamate neurotoxicity in cultured rat retinal neurons
We examined the effects of σ1 receptor agonists against glutamate-induced neurotoxicity in cultured retinal neurons. Primary cultures obtained from fetal rat retinas (16–19 d gestation) were used. The neurotoxic effect of glutamate was quantitatively assessed using the trypan blue exclusion method....
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Published in | European journal of pharmacology Vol. 342; no. 1; pp. 105 - 111 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Amsterdam
Elsevier B.V
19.01.1998
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | We examined the effects of σ1 receptor agonists against glutamate-induced neurotoxicity in cultured retinal neurons. Primary cultures obtained from fetal rat retinas (16–19 d gestation) were used. The neurotoxic effect of glutamate was quantitatively assessed using the trypan blue exclusion method. A brief exposure of retinal cultures to glutamate (500 μM) led to delayed neuronal cell death. The glutamate-induced neurotoxicity was inhibited by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,b]-cyclohepten-5,10-imine hydrogen maleate (MK-801). The σ1 receptor agonists, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)-piperazine dihydrochloride (SA4503) and (+)-pentazocine at a concentration range of 0.1~100 μM reduced the glutamate-induced neurotoxicity in a dose-dependent manner. In addition, the neuroprotective effects of both SA4503 and (+)-pentazocine were antagonized by co-treatment with N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine monohydrochloride (NE-100), a putative σ1 receptor antagonist. These findings suggest that σ1 receptor agonists protect retinal cells against glutamate-induced neurotoxicity. |
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ISSN: | 0014-2999 1879-0712 |
DOI: | 10.1016/S0014-2999(97)01450-7 |