The negative coupling between serotonin and muscarinic receptor(s) for arachidonic acid and inositol phosphates release in brain cortex synaptoneurosomes. Effect of aging.

In the present study we have investigated the relationship between serotonergic receptor(s) (5-HTR) and muscarinic cholinergic receptor (mAChR) activation, leading to the arachidonic acid (AA) release and inositol phosphates (IPs) formation in adult and aged brain cortex synaptoneurosomes. It was observed that serotonin (5-HT) almost completely inhibits carbachol-stimulated AA release in adult brain. This negative coupling between 5-HTR and mAChR probably depends on the direct stimulation of the acylation reaction coupled with 5-HT1AR. In the aged brain this type of interaction does not occur because aging eliminates carbachol and 5-HT effect. On the other hand, in aged brain, both 5-HT and carbachol more actively stimulate IPs accumulation than in adult brain. Serotonin inhibits carbachol-stimulated IPs release to the level observed during 5-HT2R activation. Our study indicates for the first time, the negative coupling between 5-HTR and mAChR for AA liberation in adult brain and a lack of this kind of receptors interaction in senescent brain. In adult brain, 5-HT1AR-stimulated AA incorporation is responsible for this coupling. Moreover, serotonin through the stimulation of 5-HT2R, suppresses mAChR-dependent IPs liberation in adult and aged brain similarly. The interactions between these two neurotransmitter receptors lead to the modification of lipid mediators formation and may have important implications in alteration of signal transduction in adult and in aged brain.