Inhibition of nitric oxide synthase prevents magnesium-free-induced epileptiform activity in guinea-pig piriform cortex neurones in vitro.
The effects of N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, were examined on Mg2+-free-induced epileptiform activity, in guinea-pig piriform cortex slices in vitro. L-NAME (0.1-1 mM) had no effect on neuronal membrane properties or electrically-evoked postsynaptic potentials (PSPs). In contrast, during superfusion of the slices with Mg2+-free solution neurones exhibited spontaneous and stimulus-evoked epileptiform potentials that were suppressed in the presence of L-NAME (100 microM) or the selective NMDA receptor antagonist DL-APV (100 microM). The inhibitory effects induced by L-NAME were reversibly reduced by L-arginine (1 mM), but not D-arginine (1 mM), the latter drug not being a substrate for NO formation. It was concluded that L-NAME can suppress epileptiform activity induced by Mg2+-free exposure primarily through a decrease in presynaptic transmitter release, although additional actions on the NMDA-receptor complex were also considered.
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Department of Pharmacology, The School of Pharmacy, London, UK.
Santarelli
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D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000187:drug effects*
D019001:Nitric Oxide Synthase; D008274:Magnesium; D019331:NG-Nitroarginine Methyl Ester