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.
Johnston
H M
HM
Department of Pharmacology, University of Glasgow, U.K.
Morris
B J
BJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D004745:Enkephalins / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D008981:Molsidomine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D014665:Vasodilator Agents; C029992:proenkephalin; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C002385:linsidomine; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C033660:preproenkephalin; D008981:Molsidomine; D006152:Cyclic GMP