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Cannabinoid receptor-dependent metabolism of 2-arachidonoylglycerol during aging.
Exp Gerontol. 2014 Jul; 55:134-42.EG

Abstract

2-Arachidonoylglycerol (2-AG) is one of the principal endocannabinoids involved in the protection against neurodegenerative processes. Cannabinoids primarily interact with the seven-segment transmembrane cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), both of which are expressed in the central nervous system (CNS). The level of 2-AG is controlled through key enzymes responsible for its synthesis or degradation. We have previously observed a deregulation of 2-AG metabolism in physiological aging. The aim of this study was to analyze how 2-AG metabolism is modulated by CB1/CB2 receptors during aging. To this end, both CB1 and CB2 receptor expression and the enzymatic activities (diacylglycerol lipase (DAGL), lysophosphatidate phosphohydrolase (LPAase) and monoacylglycerol lipase (MAGL)) involved in 2-AG metabolism were analyzed in the presence of cannabinoid receptor (CBR) agonists (WIN and JWH) and/or antagonists (SR1 and SR2) in synaptosomes from adult and aged rat cerebral cortex (CC). Our results demonstrate that: (a) aging decreases the expression of both CBRs; (b) LPAase inhibition, due to the individual action of SR1 or SR2, is reverted in the presence of both antagonists together; (c) LPAase activity is regulated mainly by the CB1 receptor in adult and in aged synaptosomes while the CB2 receptor acquires importance when CB1 is blocked; (d) modulation via CBRs of DAGL and MAGL by both antagonists occurs only in aged synaptosomes, stimulating DAGL and inhibiting MAGL activities; (e) only DAGL stimulation is reverted by WIN. Taken together, the results of the present study show that CB1 and/or CB2 receptor antagonists trigger a significant modulation of 2-AG metabolism, underlining their relevance as therapeutic strategy for controlling endocannabinoid levels in physiological aging.

Authors+Show Affiliations

Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional del Sur - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Edificio E1. Camino La Carrindanga Km 7, 8000 Bahía Blanca, Argentina.Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional del Sur - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Edificio E1. Camino La Carrindanga Km 7, 8000 Bahía Blanca, Argentina.Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional del Sur - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Edificio E1. Camino La Carrindanga Km 7, 8000 Bahía Blanca, Argentina.Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional del Sur - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Edificio E1. Camino La Carrindanga Km 7, 8000 Bahía Blanca, Argentina. Electronic address: pasquare@criba.edu.ar.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24768821

Citation

Pascual, Ana C., et al. "Cannabinoid Receptor-dependent Metabolism of 2-arachidonoylglycerol During Aging." Experimental Gerontology, vol. 55, 2014, pp. 134-42.
Pascual AC, Gaveglio VL, Giusto NM, et al. Cannabinoid receptor-dependent metabolism of 2-arachidonoylglycerol during aging. Exp Gerontol. 2014;55:134-42.
Pascual, A. C., Gaveglio, V. L., Giusto, N. M., & Pasquaré, S. J. (2014). Cannabinoid receptor-dependent metabolism of 2-arachidonoylglycerol during aging. Experimental Gerontology, 55, 134-42. https://doi.org/10.1016/j.exger.2014.04.008
Pascual AC, et al. Cannabinoid Receptor-dependent Metabolism of 2-arachidonoylglycerol During Aging. Exp Gerontol. 2014;55:134-42. PubMed PMID: 24768821.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid receptor-dependent metabolism of 2-arachidonoylglycerol during aging. AU - Pascual,Ana C, AU - Gaveglio,Virginia L, AU - Giusto,Norma M, AU - Pasquaré,Susana J, Y1 - 2014/04/24/ PY - 2014/01/06/received PY - 2014/03/27/revised PY - 2014/04/16/accepted PY - 2014/4/29/entrez PY - 2014/4/29/pubmed PY - 2015/1/13/medline KW - 2-Arachidonoylglycerol KW - Aging KW - Cannabinoid receptors KW - Diacylglycerol lipase KW - Lysophosphatidate phosphohydrolase KW - Monoacylglycerol lipase SP - 134 EP - 42 JF - Experimental gerontology JO - Exp Gerontol VL - 55 N2 - 2-Arachidonoylglycerol (2-AG) is one of the principal endocannabinoids involved in the protection against neurodegenerative processes. Cannabinoids primarily interact with the seven-segment transmembrane cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), both of which are expressed in the central nervous system (CNS). The level of 2-AG is controlled through key enzymes responsible for its synthesis or degradation. We have previously observed a deregulation of 2-AG metabolism in physiological aging. The aim of this study was to analyze how 2-AG metabolism is modulated by CB1/CB2 receptors during aging. To this end, both CB1 and CB2 receptor expression and the enzymatic activities (diacylglycerol lipase (DAGL), lysophosphatidate phosphohydrolase (LPAase) and monoacylglycerol lipase (MAGL)) involved in 2-AG metabolism were analyzed in the presence of cannabinoid receptor (CBR) agonists (WIN and JWH) and/or antagonists (SR1 and SR2) in synaptosomes from adult and aged rat cerebral cortex (CC). Our results demonstrate that: (a) aging decreases the expression of both CBRs; (b) LPAase inhibition, due to the individual action of SR1 or SR2, is reverted in the presence of both antagonists together; (c) LPAase activity is regulated mainly by the CB1 receptor in adult and in aged synaptosomes while the CB2 receptor acquires importance when CB1 is blocked; (d) modulation via CBRs of DAGL and MAGL by both antagonists occurs only in aged synaptosomes, stimulating DAGL and inhibiting MAGL activities; (e) only DAGL stimulation is reverted by WIN. Taken together, the results of the present study show that CB1 and/or CB2 receptor antagonists trigger a significant modulation of 2-AG metabolism, underlining their relevance as therapeutic strategy for controlling endocannabinoid levels in physiological aging. SN - 1873-6815 UR - https://www.unboundmedicine.com/medline/citation/24768821/Cannabinoid_receptor_dependent_metabolism_of_2_arachidonoylglycerol_during_aging_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0531-5565(14)00129-6 DB - PRIME DP - Unbound Medicine ER -