Metabolism of anandamide and 2-arachidonoylglycerol: An historical overview and some recent developments
Tóm tắt
Anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol are the two endogenous agonists of cannabinoid receptors discovered to date. Like other eicosanoids, and unlike classical neuromodulators, these two compounds are synthesized by neurons on demand, i.e., their biosynthesis, rather than release, is stimulated by Ca2+ influx and cell membrane depolarization. Both endocannabinoids can be produced from membrane phosphoglycerides through the action of phospholipases, althoughde novo pathways have also been suggested. Once released by cells, the action of both anandamide and 2-arachidonoylglycerol is terminated—after their diffusion through the cell membrane—by the hydrolysis of the amide or ester bonds to yield arachidonic acid, which is then immediately reincorporated into phospholipids. One enzyme, fatty acid amide hydrolase, catalyzes the hydrolysis of both endocannabinoids in nervous and nonnervous cells. This enzyme also recognizesN-palmitoylethanolamine, an antiinflammatory congener of anandamide, with a catalytic efficiency that depends on the cell type under study. However, the existence of different isozymes with different affinity for anandamide andN-palmitoylethanolamine has not been investigated. Moreover, little work has been performed on the regulation of anandamide formation and breakdown, and several open questions remain as to the possible biosynthetic and degradative mechanisms of cannabimimetic 2-arachidonoylglycerol in nucleated blood cells such as macrophages. Finally, the co-existence of both endocannabinoids in invertebrates has not been fully established. Here we briefly review the state of the art, and present new data from our laboratory, on these four largely unexplored aspects of endocannabinoid metabolism.
Tài liệu tham khảo
Devane, W.A., Hanus, L., Breuer, A., Pertwee, R.G., Stevenson, L.A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., and Mechoulam, R. (1992) Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor,Science 258, 1946–1949.
Schmid, H.H.O., Schmid, P.C., and Natarajan, V. (1990)N-Acylated Glycerophospholipids and Their Derivatives,Prog. Lipid Res. 29, 1–43.
Mechoulam, R., Ben-Shabat, S., Hanus, L., Ligumsky, M., Kaminski, N.E., Schatz, A.R., Gopher, A., Almog, S., Martin, B.R., Compton, D.R., Pertwee, R.G., Griffin, G., Bayewitch, M., Barg, J., and Vogel, Z. (1995) Identification of an Endogenous 2-Monoglyceride, Present in Canine Gut, That Binds to Cannabinoid Receptors,Biochem. Pharmacol. 50, 83–90.
Sugiura, T., Kondo, S., Sukagawa, A., Nakane, S., Shinoda, A., Itoh, K., Yamashita, A., and Waku, K. (1995) 2-Arachidonoylglycerol: A Possible Endogenous Cannabinoid Receptor Ligand in Brain,Biochem. Biophys. Res. Commun. 215, 89–97.
Di Marzo, V., Melck, D., Bisogno, T., and De Petrocellis, L. (1998) Endocannabinoids: Endogenous Cannabinoid Receptor Ligands with Neuromodulatory Action,Trends Neurosci. 21, 521–528.
Di Marzo, V. (1998) Endocannabinoids and Other Fatty Acid Derivatives with Cannabimimetic Properties: Biochemistry and Possible Physiopathological Relevance,Biochim. Biophys. Acta 1392, 153–175.
Di Marzo, V., Fontana, A., Cadas, H., Schinelli, S., Cimino, G., Schwartz, J.-C., and Piomelli, D. (1994) Formation and Inactivation of Endogenous Cannabinoid Anandamide in Central Neurons,Nature 372, 686–691.
Sugiura, T., Kondo, S., Sukagawa, A., Tonegawa, T., Nakane, S., Yamashita, A., Ishima, Y., and Waku, K. (1996) Transacylase-Mediated and Phosphodiesterase-Mediated Synthesis ofN-Arachidonoylethanolamine, an Endogenous Cannabinoid-Receptor Ligand, in Rat Brain Microsomes. Comparison with the Synthesis from Free Arachidonic Acid and Ethanolamine,Eur. J. Biochem. 240, 53–62.
Bisogno, T., Maurelli, S., Melck, D., De Petrocellis, L., and Di Marzo, V. (1997) Biosynthesis, Uptake, and Degradation of Anandamide and Palmitoylethanolamide in Leukocytes,J. Biol. Chem. 272, 3315–3323.
Kuwae, T., Schmid, P.C., and Schmid, H.H.O. (1997) Alterations of Fatty Acyl Turnover in Macrophage Glycerolipids Induced by Stimulation. Evidence for Enhanced Recycling of Arachidonic Acid,Biochim. Biophys. Acta 1344, 74–86.
Cadas, H., Gaillet, S., Beltramo, M., Venance, L., and Piomelli, D. (1996) Biosynthesis of an Endogenous Cannabinoid Precursor in Neurons and Its Control by Calcium and cAMP,J. Neurosci. 16, 3934–3942.
Ueda, N., Kurahashi, Y., Yamamoto, S., and Tokunaga, T. (1995) Partial Purification and Characterization of the Porcine Brain Enzyme Hydrolyzing and Synthesizing Anandamide,J. Biol. Chem. 270, 23823–23827.
Cravatt, B.F., Giang, D.K., Mayfield, S.P., Boger, D.L., Lerner, R.A., and Gilula, N.B. (1996) Molecular Characterization of an Enzyme That Degrades Neuromodulatory Fatty Acid Amides,Nature 384, 83–87.
Thomas, E.A., Cravatt, B.F., Danielson, P.E., Gilula, N.B., and Sutcliffe, J.G. (1997) Fatty Acid Amide Hydrolase, the Degradative Enzyme for Anandamide and Oleamide, Has Selective Distribution in Neurons Within the Rat Central Nervous System,J. Neurosci. Res. 50, 1047–1052.
Bisogno, T., Sepe, N., Melck, D., Maurelli, S., De Petrocellis, L., and Di Marzo, V. (1997) Biosynthesis, Release and Degradation of the Novel Endogenous Cannabimimetic Metabolite 2-Arachidonoyl-glycerol in Mouse Neuroblastoma Cells,Biochem. J. 322, 671–677.
Stella, N., Schweitzer, P., and Piomelli, D. (1997) A Second Endogenous Cannabinoid That Modulates Long-Term Potentiation,Nature 388, 773–778.
Gammon, C.M., Allen, C., and Morell, P. (1989) Bradykinin Stimulates Phosphoinositide Hydrolysis and Mobilization of Arachidonic Acid in Dorsal Root Ganglion Neurons,J. Neurochem. 53, 95–101.
Prescott, S.M., and Majerus, P.M. (1983) Characterization of 1,2-Diacylglycerol Hydrolysis in Human Platelets. Demonstration of an Arachidonoyl-monoacylglycerol Intermediate,J. Biol. Chem. 258, 764–769.
Varga, K., Wagner, J.A., Bridgen, D.T., and Kunos, G. (1998) Platelet- and Macrophage-Derived Endogenous Cannabinoids Are Involved in Endotoxin-Induced Hypothension,FASEB J. 12, 1035–1044.
Di Marzo, V., Bisogno, T., Sugiura, T., Melck, D., and De Petrocellis, L. (1998) The Novel Endogenous Cannabinoid 2-Arachidonoylglycerol Is Inactivated by Neuronal and Basophillike Cells: Connections with Anandamide,Biochem. J. 331, 15–19.
Goparaju, S.K., Ueda, N., Yamaguchi, H., and Yamamoto, S. (1998) Anandamide Amidohydrolase Reacting with 2-Arachidonoylglycerol, Another Cannabinoid Receptor Ligand,FEBS Lett. 422, 69–73.
Wagner, J.A., Varga, K., Ellis, E.F., Rzigalinski, B.A., Martin, B.R., and Kunos, G. (1997) Activation of Peripheral CB1 Cannabinoid Receptors in Haemorrhagic Shock,Nature 390, 518–521.
Schmid, P.C., Paria, B.C., Krebsbach, R.J., Schmid, H.H.O., and Dey, S.K. (1997) Changes in Anandamide Levels in Mouse Uterus Are Associated with Uterine Receptivity for Embryo Implantation,Proc. Natl. Acad. Sci. USA 94, 4188–4192.
Katayama, K., Ueda, N., Kurahashi, Y., Suzuki, H., Yamamoto, S., and Kato, I. (1997) Distribution of Anandamide Amidohydrolase in Rat Tissues with Special Reference to Small Intestine,Biochim. Biophys. Acta 1347, 212–218.
Bisogno, T., Melck, D., De Petrocellis, L., and Di Marzo, V. (1999) Phosphatidic Acid as the Biosynthetic Precursor of the Endocannabinoid 2-Arachidonoylglycerol in Intact Mouse Neuroblastoma Cells Stimulated with Ionomycin,J. Neurochem. 72, 2113–2119.