title: Glutamate Release from Chick Retina Explants in Response to Domoic Acid.
abstract: Release of endogenous glutamate (GLU) evoked by an exogenous excitotoxin such as kainate can contribute to central nervous system (CNS) excitotoxicity. In this study, the possibility that this mechanism accounts for reported domoic acid (DOM) toxicity was investigated using the isolated chick retina. Exposing retinas to 0-100 µM DOM for 40 min caused an increased efflux of lactate dehydrogenase (LDH) and a dose-related release of GLU into the incubation medium. Neuronal damage following exposure to DOM was confirmed by histologic examination of the retina. DOM-induced GLU release occurred at 27 and 37 degrees C and was more pronounced in medium containing a low calcium concentration (0.1 mM). In contrast, K(+) evoked GLU release occurred only at 37 degrees C in 2 mM calcium, but not at 27 degrees C. DOM-induced GLU release was reduced in hyperosmolar medium (medium 1 100 mM sucrose). Similar to GLU release, the LDH release occurred at both 27 and 37 degrees C and was reduced in hyperosmolar medium. These results suggest that an increase in membrane permeability secondary to osmotic swelling and lysis rather than a calcium-dependent vesicular exocytosis mechanism is responsible for GLU and LDH release. GYKI 52466, a selective noncompetitive antagonist of the non-NMDA receptor, prevented neuronal degeneration and GLU/LDH release. MK-801, a highly potent noncompetitive NMDA receptor blocker, reduced neuronal injury (33% decrease in LDH release), but did not reduce DOM-evoked GLU release significantly. Typical excitotoxic lesions were produced at all concentrations tested, with amacrine cells in the inner nuclear layer being the most severely affected. Released GLU contributed to further excitotoxic injury, exacerbating the neurotoxic action of DOM in isolated embryonic chick retina.
authors.affiliation: Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059.
authors.initials: CI
authors.lastname: Nduaka
authors.initials: RE
authors.lastname: Taylor
authors.initials: S
authors.lastname: Green
authors.initials: T
authors.lastname: Flynn
authors.initials: V
authors.lastname: Sathyamoorthy
authors.initials: RL
authors.lastname: Sprando
authors.initials: JN
authors.lastname: Johannessen