Possible Interaction: Arachidonic Acid and Serotonin

“Interestingly, … AA … 5-HT was, also, blocked by the 5-HT receptor blockers cyproheptadine (IC50=22.0±7 μmol/L), ketanserin (IC50=152±23 μmol/L), phospholipase …; IC50=6.1±0.8 μmol/L), and mitogen activated protein kinase (MAPK) inhibitor (PD98059; IC50=3.8±0.5 μmol/L).”

“Moreover, the observed synergistic effect of AA with 5-HT on platelets was inhibited by different cyclooxygenase (COX) inhibitors, namely ibuprofen and celecoxib, with half maximal inhibitory effect (IC50) values of 18.0±1.8 and 15.6±3.4 μmol/L, respectively.”

“The results demonstrated that 5-HT had no or negligible effect on aggregation but it did potentiate the aggregation response of AA.”

“RESULTS Subthreshold concentration of 5- T (2 micromol/L) potentiated the effect of low dose of AA (0 .2 mmol/L) in human platelets.”

“In endothelium intact strips, arachidonic acid (AA;1 microM) potentiates the contractile response to 5-HT , whereas the response was reduced by indomethacin (INDO;10 microM).”

“Stimulation with 10(-4) M 5-HT , followed by incubation with 3 microM AA and 1 microCi [3H]AA for 5 min, resulted in a decrease in the formation of thromboxane B2 (TxB2) and 12-hydroxyheptadecatrienoic acid (HHT, P less than 0.05).”

“To examine the hypothesis that released 5-HT has a modulatory effect on the metabolism of AA by platelets, we incubated nonaggregating washed human platelets with 5-HT in the presence of [3H]AA.”

“ AA also increased the turnover of dopamine (DA), noradrenaline (NA), and serotonin ( 5-HT) in the amygdala and increased the prostaglandin (PG)E(2) level in the hippocampus.”

“The sustained calcium signal to 5-HT was partly blocked by inhibitors of arachidonic acid production (RHC-80267 and isotetrandrine) and mimicked by application of exogenous arachidonic acid.”

“Our results show that cannabinoids and arachidonic acid inhibit DA and 5-HT uptake into rat neocortical synaptosomes.”

“ Serotonin inhibited cAMP production, had no effect on inositol phosphate production, and activated phospholipase A2, causing release of arachidonic acid.”

“The effects (maximal at 5 min) lasted 1 h. By using fluorophotometry and RIA, it was seen that Pro suppressed the release of 5-HT from platelets during aggregation induced by collagen, AA , or TMVM in vitro.”

“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.”