Serotonin, a potent modulator of arachidonic acid turnover, interaction with glutamatergic receptor in brain cortex

Brain cortex synaptoneurosomes actively incorporated [14C]arachidonic acid (AA) into lipids. Serotonin (5-HT), at a concentration range of 10 microM-1 mM, significantly stimulates the incorporation of AA mainly into phosphatidylinositol (PI) of brain cortex synaptoneurosomes. The stimulation rate of AA incorporation by 5-HT was the same in the presence and absence of lysophosphatidylinositol (LPI). However, in the absence of LPI some stimulation of AA uptake was also observed into phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid. Buspirone, an agonist of 5-HT1A receptor, has a similar effect on AA incorporation into membrane lipids as serotonin itself. Moreover, ketanserin, an antagonist of 5-HT2 receptor, also induces activation of AA incorporation into membrane lipids. On the other hand, glutamate, in a concentration dependent manner, significantly inhibits AA uptake into PI and also has some inhibitory action on AA uptake into the other lipids. Serotonin itself and the agonist of 5-HT1A receptor through the activation of AA turnover counteract glutamate-induced inhibition of AA uptake into lipids of brain cortex. Our results indicated that serotonin directly, through the specific receptors, or indirectly, through the interaction with glutamatergic receptors, modulates turnover and the level of arachidonic acid in the brain.