Nitric oxide alters proenkephalin and prodynorphin gene expression in hippocampal granule cells.

Application of N-methyl-D-aspartate on to the dendrites of hippocampal granule cells dramatically decreased prodynorphin messenger RNA levels in the affected cells while increasing proenkephalin messenger RNA levels. Sin-1 molsidomine (an agent which releases nitric oxide) and 8-bromo-cyclic GMP were similarly effective, and the actions of sin-1 molsidomine were blocked by inhibition of cyclic GMP-dependent protein kinase. Since, in this region, dynorphins act to inhibit potentiation of synaptic transmission, while enkephalins have excitatory effects, this switch in opioid gene expression is likely to have a prolonged effect on the efficiency of the mossy fibre synapses. In addition, the results demonstrate a powerful role for nitric oxide in the long-term regulation of hippocampal excitability.