Aged-related changes in endocannabinoid hydrolysis in rat cerebral cortex synaptosomes

PASCUAL, A.C.; GIUSTO, N.M.; PASQUARÉ, S.J.

Potrero de los Funes, San Luis

Congreso; XLIVII Reunión Anual de la Sociedad de Investigación en Bioquímica y Biología Molecular (SAIB); 2011

The enzymes monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) are both involved in the hydrolysis of endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA), respectively. The aim of this study was to evaluate how the breakdown of 2-AG and AEA was modified by agonists and antagonists of CB1 and CB2 receptors during physiological aging. Cerebral cortex synaptosomes from adult (3 mo) and aged (28 mo) rats were isolated by differential centrifugation and purified in ficoll gradients. MAGL and FAAH activities were assayed using 2-arachidonoyl-[3H]glycerol or arachidonoyl-[3H]etanolamine, respectively; and their products, [3H]glycerol and [3H]etanolamine, were quantified from aqueous phase by liquid scintillation. The presence and activity of both enzymes was observed in synaptosomes. MAGL activity was increased and FAAH activity was decreased by aging. MAGL and FAAH activities in aged synaptosomes were abolished by the action of their respective inhibitors. CB1 and CB2 agonist (WIN) did not modify MAGL activity although CB1 antagonist (SR1) increased MAGL activity in adults and decreased it in aged synaptosomes. Our results show important differences in endocannabinoid metabolism during aging, which are modulated through cannabinoid receptors.