Endothelin-1 enhances glutamate-induced retinal cell death, possibly through ETA receptors.
PURPOSE: To determine the modification of the glutamate-induced death of retinal neurons by endothelin (ET)-1. METHODS: Cultured retinal neurons from fetal rats were exposed to glutamate (1.0 mM) alone or glutamate with ET-1 (10(-10)-10(-7)M) for 10 minutes. Neuronal death was assessed by the trypan blue exclusion or TUNEL assays at 2, 6, and 24 hours after the exposure. The effects of adding BQ-123 or BQ-788, ET(A), and ET(B) receptor antagonists, respectively, in combination with ET-1 was also assessed. RESULTS: Immunohistochemical analyses showed that the ETs as well as ET(A) and ET(B) receptors were expressed on cultured retinal neurons consisting mainly of amacrine cells. A brief exposure of the cultured retinal neurons to glutamate alone significantly increased the number of dead cells, and the addition of ET-1 with glutamate caused a further significant increase in retinal neuronal death compared with the cells exposed to glutamate alone. A significant increase in neuronal death was detected at doses of 10 nM of ET-1 and higher after a 24-hour exposure (P < 0.05, Dunnett), whereas brief exposure of neurons to up to 1 microM ET-1 alone did not cause delayed cell death of neurons. BQ-123 (10 nM) suppressed the enhancement of retinal toxicity caused by ET-1 (10 nM), whereas BQ-788 had no significant effect. CONCLUSIONS: These results indicate that ET-1 enhances glutamate-induced retinal cell death, possibly through ET(A) receptors. ET-1 may act synergistically with glutamate to damage retinal neurons under hypoxic conditions.[1]References
- Endothelin-1 enhances glutamate-induced retinal cell death, possibly through ETA receptors. Kobayashi, T., Oku, H., Fukuhara, M., Kojima, S., Komori, A., Ichikawa, M., Katsumura, K., Kobayashi, M., Sugiyama, T., Ikeda, T. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
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