NO-producing compounds transform neuron responses to glutamate.

We have previously shown that NO increases the excitatory effects of glutamate and blocks the desensitization of neurons to glutamate in the brain of the common snail. The aim of the present work was to identify the possible effect of NO on inhibitory responses to glutamate in the neurons of this mollusk. Electrophysiological investigations were performed on three identified neurons. The results showed that glutamate (0.05-0.1 mM) initially induced hyperpolarization and blocked the spike activity of these neurons. Simultaneous exposure to glutamate and the NO donor nitroprusside or preincubation with an NO donor had the effect that cells again responded to glutamate with depolarization and excitation. The transformed excitatory response lasted several minutes and could be reproduced even after 24 h of washing. The NO synthase blocker monomethylarginine blocked the excitatory response to glutamate. Another agonist of glutamate receptors, N-methyl-D-aspartate (NMDA, 0.1-1 mM), initially had excitatory effects on these neurons; this effect was significantly enhanced after transformation of the response to glutamate by NO donors. The results obtained here show that NO is involved in transforming the inhibitory responses to glutamate to excitatory responses, and that this effect may be mediated by NMDA-type receptors.