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  • Title: Activation of serotonergic 5-HT1A receptor reduces Ca(2+)- and glutamatergic receptor-evoked arachidonic acid and No/cGMP release in adult hippocampus.
    Author: Strosznajder J, Chalimoniuk M, Samochocki M.
    Journal: Neurochem Int; 1996 Apr; 28(4):439-44. PubMed ID: 8740452.
    Abstract:
    Stimulation of glutamatergic NMDA receptor in adult rat hippocampal synaptoneurosomes induces statistically significant Ca(2+)-dependent liberation of arachidonic acid (AA) and nitric oxide (NO)-activated cGMP synthesis. NMDA acting for 5 min at 100 microM markedly increases, by approx. 25%, Ca(2+)-mediated AA release from phospholipids of hippocampal synaptoneurosomes. Prolonged stimulation of NMDA receptor up to 10 min has smaller stimulatory effect and enhances AA release by about 6%. Moreover, NMDA activates NO-dependent cGMP production by approx. 5 times more than the Ca2+ itself. Release of both these second messengers is completely blocked by the competitive NMDA antagonist, APV (100 microM). The NMDA-mediated cGMP elevation completely depends on NO action, and is abolished by the specific inhibitor of NO synthase, NG-nitro-L-arginine. Moreover, serotonin at 10 microM in the presence of 10 microM pargyline, potently decreases both Ca(2+)- and NMDA receptor-mediated AA and cGMP release in hippocampal synaptoneurosomes. The agonist of 5-HT1A receptor, buspirone, in a way similar to serotonin itself, counteracts the Ca(2+)- and also NMDA receptor-evoked AA release and cGMP accumulation. An antagonist of 5-HT1A receptor, NAN-190, eliminates the effect of serotonin and buspirone on AA and NO/cGMP liberation. An antagonist of serotonergic 5-HT2 receptor, ketanserin, has no effect on the Ca2+ and serotonin action. These results indicate that serotonin, through 5-HT1A receptor, potently antagonizes the action of excitatory amino acid for AA release and NO/cGMP synthesis in the adult rat hippocampus. In conclusion, the interaction of serotonin with the glutamatergic system in the hippocampus may play an important role in the modulation of a signal transduction pathway, and by this molecular mechanism serotonin may exert a neuroprotective effect on hippocampal neurons.
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