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Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism.
Mol Pharmacol 2004; 65(4):999-1007MP

Abstract

Microglia, as phagocytes and antigen-presenting cells in the central nervous system, are activated in such disease processes as stroke and multiple sclerosis. Because peripheral macrophages are capable of producing endocannabinoids, we have examined endocannabinoid production in a macrophage-colony stimulating factor (M-CSF)-dependent rat microglial cell line (RTMGL1) using reversed phase high-pressure liquid chromatography and liquid chromatography-mass spectroscopy. We determined that cultured microglial cells produce the endocannabinoid 2-arachidonylglycerol (2-AG) as well as anandamide in smaller quantities. When 2-AG, but not anandamide, is added exogenously, RTMGL1 microglia increase their proliferation. This increased proliferation is blocked by an antagonist of the CB(2) receptor N-[(1S)endo-1,3,3-trimethyl bicyclo heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) and mimicked by the CB(2) receptor-specific agonist 1,1-dimethylbutyl-1-deoxy-Delta(9)-tetrahydrocannabinol (JWH133). Accompanying the increase in proliferation seen with 2-AG is an increase in active ERK1 that is also blocked with SR144528. The RTMGL1 microglial cells, which exist in a primed state, express the CB(1) and CB(2) receptors as demonstrated by reverse transcription-polymerase chain reaction and immunostaining. The CB(2) receptor in untreated cells is expressed both at the cell surface and internally, and exposure of the cells to 2-AG significantly increases receptor internalization. These data suggest that 2-AG activation of CB(2) receptors may contribute to the proliferative response of microglial cells, as occurs in neurodegenerative disorders.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226-0509, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15044630

Citation

Carrier, Erica J., et al. "Cultured Rat Microglial Cells Synthesize the Endocannabinoid 2-arachidonylglycerol, Which Increases Proliferation Via a CB2 Receptor-dependent Mechanism." Molecular Pharmacology, vol. 65, no. 4, 2004, pp. 999-1007.
Carrier EJ, Kearn CS, Barkmeier AJ, et al. Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism. Mol Pharmacol. 2004;65(4):999-1007.
Carrier, E. J., Kearn, C. S., Barkmeier, A. J., Breese, N. M., Yang, W., Nithipatikom, K., ... Hillard, C. J. (2004). Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism. Molecular Pharmacology, 65(4), pp. 999-1007.
Carrier EJ, et al. Cultured Rat Microglial Cells Synthesize the Endocannabinoid 2-arachidonylglycerol, Which Increases Proliferation Via a CB2 Receptor-dependent Mechanism. Mol Pharmacol. 2004;65(4):999-1007. PubMed PMID: 15044630.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism. AU - Carrier,Erica J, AU - Kearn,Christopher S, AU - Barkmeier,Andrew J, AU - Breese,Nicole M, AU - Yang,Wenqi, AU - Nithipatikom,Kasem, AU - Pfister,Sandra L, AU - Campbell,William B, AU - Hillard,Cecilia J, PY - 2004/3/27/pubmed PY - 2004/4/22/medline PY - 2004/3/27/entrez SP - 999 EP - 1007 JF - Molecular pharmacology JO - Mol. Pharmacol. VL - 65 IS - 4 N2 - Microglia, as phagocytes and antigen-presenting cells in the central nervous system, are activated in such disease processes as stroke and multiple sclerosis. Because peripheral macrophages are capable of producing endocannabinoids, we have examined endocannabinoid production in a macrophage-colony stimulating factor (M-CSF)-dependent rat microglial cell line (RTMGL1) using reversed phase high-pressure liquid chromatography and liquid chromatography-mass spectroscopy. We determined that cultured microglial cells produce the endocannabinoid 2-arachidonylglycerol (2-AG) as well as anandamide in smaller quantities. When 2-AG, but not anandamide, is added exogenously, RTMGL1 microglia increase their proliferation. This increased proliferation is blocked by an antagonist of the CB(2) receptor N-[(1S)endo-1,3,3-trimethyl bicyclo heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) and mimicked by the CB(2) receptor-specific agonist 1,1-dimethylbutyl-1-deoxy-Delta(9)-tetrahydrocannabinol (JWH133). Accompanying the increase in proliferation seen with 2-AG is an increase in active ERK1 that is also blocked with SR144528. The RTMGL1 microglial cells, which exist in a primed state, express the CB(1) and CB(2) receptors as demonstrated by reverse transcription-polymerase chain reaction and immunostaining. The CB(2) receptor in untreated cells is expressed both at the cell surface and internally, and exposure of the cells to 2-AG significantly increases receptor internalization. These data suggest that 2-AG activation of CB(2) receptors may contribute to the proliferative response of microglial cells, as occurs in neurodegenerative disorders. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/15044630/Cultured_rat_microglial_cells_synthesize_the_endocannabinoid_2_arachidonylglycerol_which_increases_proliferation_via_a_CB2_receptor_dependent_mechanism_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15044630 DB - PRIME DP - Unbound Medicine ER -