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Cyclooxygenase-2 inhibitor celecoxib inhibits glutamate release in rat cerebrocortical nerve terminals by suppression of presynaptic voltage-dependent calcium influx

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Lin, T. Y.; Lu, C. W.; Huang, S. K.; Wang, S. J.

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European Journal of Anaesthesiology (EJA): June 2013 - Volume 30 - Issue - p 5-6
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Background and Goal of Study: Cyclooxygenase-2 (COX-2) inhibitors have been widely utilized for the treatment of various inflammatory conditions to reduce pain and inflammation. In addition, COX-2 inhibitors have demonstrated a potential neuroprotective effect in recent studies. Considering the fact that excessive glutamatergic synaptic transmission can cause neuronal excitotoxicity, we investigated whether COX-2 inhibitors could influence glutamate release from isolated nerve terminals (synaptosomes).

Materials and Methods: Truncated nerve terminals purified from Sprague-Dawley rat cerebral cortex were used to examine the effect of a COX-2 inhibitor celecoxib on glutamate release evoked by 4-aminopyridine (4-AP). The effects of celecoxib on the membrane potential and calcium ions influx were also examined by DiSC3(5) and Fura-2, respectively. Furthermore, different calcium channel blockers were used to investigate which part of the calcium source was involved in the effect of celecoxib.

Results and Discussion: Results showed that celecoxib inhibited 4-AP-evoked release of glutamate from rat cerebrocortical nerve terminals. The effect of celecoxib was prevented by chelating the intracellular calcium ions and by the vesicular transporter inhibitor bafilomycin A1, but was insensitive to the glutamate transporter inhibitor. Celecoxib reduced the depolarization-induced increase in cytosolic free calcium ions concentration, but did not alter 4-AP-mediated depolarization.

Furthermore, the inhibitory effect of celecoxib on evoked glutamate release were abolished by blocking the N-type and P/Q-type channels, but not by blocking ryanodine receptors or mitochondrial Na+/Ca2+ exchange.

Conclusion(s): Our results suggest that celecoxib inhibits glutamate release from rat cortical nerve terminals through the suppression of presynaptic voltage-dependent calcium entry which may delineate the possible neuroprotective mechanism of COX-2 inhibitors.

Acknowledgements: This work was supported by grant from the National Science Council of Taiwan, Republic of China (NSC 101-2314-B-418-001)

© 2013 European Society of Anaesthesiology