Protective effect of GV150526A on the glutamate-induced changes in basal and electrically-stimulated cytosolic Ca ++ in primary cultured cerebral cortical cells

Glutamate-induced changes in intracellular free Ca ++ concentration ([Ca ++] i) were recorded in resting and electrically-stimulated primary cultures of rat cerebral cortical cells, employing the Ca ++ indicator Fura 2. A brief (10 min) exposure to glutamate led to a concentration-dependent basal [C...

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Published in:	Neurochemistry international 1998-04, Vol.32 (4), p.345-351
Main Authors:	Tomasini, M.C., Antonelli, T., Trist, D.G., Reggiani, A., Beani, L., Bianchi, C.
Format:	Article
Language:	eng
Subjects:	Animals Biological and medical sciences Calcium - metabolism Cells, Cultured Cerebral Cortex - drug effects Cerebral Cortex - metabolism Drug Interactions Electric Stimulation Excitatory Amino Acid Antagonists - pharmacology Glutamic Acid - toxicity Indoles - pharmacology Medical sciences Neuropharmacology Neuroprotective agent Pharmacology. Drug treatments Piperidines - pharmacology Quinoxalines - pharmacology Rats Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
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Summary:	Glutamate-induced changes in intracellular free Ca ++ concentration ([Ca ++] i) were recorded in resting and electrically-stimulated primary cultures of rat cerebral cortical cells, employing the Ca ++ indicator Fura 2. A brief (10 min) exposure to glutamate led to a concentration-dependent basal [Ca ++] i increase, measured 30 min after glutamate removal. In order to unmask more subtle modifications in [Ca ++] i movements associated with neurosecretion, the glutamate effect was also studied in electrically-stimulated cells. The application of trains (10 s) of electrical pulses (intensity 30 mA, duration 1 ms) induced frequency-related Na +- and Ca ++-dependent [Ca ++] i transients. A 5 min treatment with 50 μM glutamate reduced to 48% the electrically-evoked [Ca ++] i transients, evaluated 30 min after glutamate challenge. The neuroprotective effect of sodium 4-6-dichloro-3-[(E)]-3-( N-phenyl)propenamide]indole-2-carboxylate (GV150526A), a new indole derivative with high affinity and selectivity for the glycine site of the NMDA receptor-channel complex, was compared with that of dl-2-amino-5-phosphonopentanoic acid (AP5), infenprodil, 7-chlotokynurenic acid and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)-quinoxaline (NBOX) on glutamate-induced [Ca ++] i changes in resting and electrically-stimulated cells. In both experimental conditions, GV150526A showed to be the most potent compound. Moreover, GV150526A and 7-chlorokynurenic acid were 2–3 times more active in stimulated neurons than in resting neurons, indicating a major involvement of the glycine site in the protection of the cells kept in an active state.
ISSN:	0197-0186 1872-9754