The article "Formation and Inactivation of Endogenous Cannabinoid Anandamide in Central Neurons" by Vincenzo Di Marzo, Angelo Fontana, Hugues Cadas, et al., published in Nature in 1994, investigates the mechanisms of anandamide formation, release, and inactivation in brain neurons. Anandamide, a brain arachidonate derivative, is identified as a potential endogenous cannabinoid. The study shows that anandamide is produced and released from cultured brain neurons in a calcium ion-dependent manner when stimulated with membrane-depolarizing agents. The formation of anandamide occurs through phospholipase-mediated cleavage of a novel phospholipid precursor, N-arachidonoyl-phosphatidylethanolamine (N-acyl-PE). This process is regulated by phospholipase D activity and is independent of energy-dependent condensation of arachidonate and ethanolamine. The study also demonstrates that anandamide is rapidly cleared from neuronal cultures through a carrier-mediated uptake process, followed by hydrolytic degradation to ethanolamine and arachidonate. These findings support the role of anandamide as an endogenous neuronal messenger and suggest that it may participate in cellular signaling processes.The article "Formation and Inactivation of Endogenous Cannabinoid Anandamide in Central Neurons" by Vincenzo Di Marzo, Angelo Fontana, Hugues Cadas, et al., published in Nature in 1994, investigates the mechanisms of anandamide formation, release, and inactivation in brain neurons. Anandamide, a brain arachidonate derivative, is identified as a potential endogenous cannabinoid. The study shows that anandamide is produced and released from cultured brain neurons in a calcium ion-dependent manner when stimulated with membrane-depolarizing agents. The formation of anandamide occurs through phospholipase-mediated cleavage of a novel phospholipid precursor, N-arachidonoyl-phosphatidylethanolamine (N-acyl-PE). This process is regulated by phospholipase D activity and is independent of energy-dependent condensation of arachidonate and ethanolamine. The study also demonstrates that anandamide is rapidly cleared from neuronal cultures through a carrier-mediated uptake process, followed by hydrolytic degradation to ethanolamine and arachidonate. These findings support the role of anandamide as an endogenous neuronal messenger and suggest that it may participate in cellular signaling processes.