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 ser otonergic receptor(s) (5-HTR) and muscarinic cholinergic receptor (mAC hR) activation, leading to the arachidonic acid (AA) release and inosi tol phosphates (IPs) formation in adult and aged brain cortex synapton eurosomes. It was observed that serotonin (5-HT almost completely inhi bits carbachol-stimulated AA release in adult brain. This negative cou pling between 5-HTR and mAChR probably depends on the direct stimulati on of the acylation reaction coupled with 5-HT(1A)R. In the aged brain this type of interaction does not occur because aging eliminates carb achol and 5-HT effect. On the other hand, in aged brain, both 5-HT and carbachol more actively stimulate IPs accumulation than in adult brai n. Serotonin inhibits carbachol-stimulated IPs release to the level ob served during 5-HT(2)R activation. Our study indicates for the first t ime, the negative coupling between 5-HTR and mAChR for AA liberation i n adult brain and a lack of this kind of receptors interaction in sene scent brain. In adult brain, 5-HT(1A)R-stimulated AA incorporation is responsible for this coupling. Moreover, serotonin through the stimula tion of 5-HT(2)R, suppresses mAChR-dependent IPs liberation in adult a nd aged brain similarly. The interactions between these two neurotrans mitter receptors lead to the modification of lipid mediators formation and may have important implications in alteration of signal transduct ion in adult and in aged brain.