Sequential activation of soluble guanylate cyclase, protein kinase G and cGMP-degrading phosphodiesterase is necessary for proper induction of long-term potentiation in CA1 of hippocampus. Alterations in hyperammonemia.

摘要: Abstract Long-term potentiation (LTP) is a long-lasting enhancement of synaptic transmission efficacy and considered the base for some forms learning memory. Nitric oxide (NO)-induced formation cGMP involved in hippocampal LTP. We have studied slices effects application tetanus to induce LTP on metabolism mechanisms by which modulates Tetanus induced transient rise cGMP, reaching maximum at 10 s decreasing below basal levels 5 min after tetanus, remaining 60 min. Soluble guanylate cyclase (sGC) activity increased returned The decrease was due sustained tetanus-induced increase cGMP-degrading phosphodiesterase activity, remained activated 60 min tetanus. Tetanus-induced activation PDE were prevented inhibiting protein kinase G (PKG). This indicates that initial activates PKG phosphorylates (and activates) PDE, which, turn, degrades cGMP. Inhibition sGC, or impairs LTP, indicating proper induction involves sGC followed cGMP-dependent kinase, phosphodiesterase, resulting reduction content. Hyperammonemia main responsible neurological alterations found liver disease hepatic encephalopathy, including impaired intellectual function. hippocampus altering modulation this sGC-PKG-cGMP-degrading pathway. Exposure 1 mM ammonia completely prevents impairing PKG-mediated phosphodiesterase. impairment loss maintenance hyperammonemia, may be also cognitive patients with hyperammonemia encephalopathy.