Tags

Type your tag names separated by a space and hit enter

The cannabinoid WIN 55,212-2-mediated protection of dentate gyrus granule cells is driven by CB1 receptors and modulated by TRPA1 and Cav 2.2 channels.
Hippocampus. 2011 May; 21(5):554-64.H

Abstract

Cannabinoids regulate numerous physiological and pathological events like inflammation or neurodegeneration via CB(1) and CB(2) receptors. The mechanisms behind cannabinoid effects show a high variability and may also involve transient receptor potential channels (TRP) and N-type voltage-gated Ca(2+) channels (Ca(v) 2.2). In the present study we investigated the neuroprotective effects of the synthetic cannabinoid WIN 55,212-2 (WIN) on dentate gyrus (DG) granule cells and elucidated the involvement of TRP and Ca(v) 2.2 that are shown to participate in inflammatory processes. Organotypic hippocampal slice cultures were excitotoxically lesioned using NMDA and subsequently incubated with different WIN concentrations (0.001-10 μM). WIN showed neuroprotective properties in an inverse concentration-dependent manner, most effectively at 0.01 μM. The CB(1) receptor antagonist AM251 blocked neuroprotection mediated by WIN whereas the CB(2) receptor antagonist AM630 showed no effects. Application of the TRPA1 blocker HC-030031 enhanced the neuroprotective efficacy of high (10 μM) WIN concentrations and the number of degenerating neurons became equal to that seen after application of the most effective WIN dose (0.01 μM). In contrast, the application of TRPA1 agonist icilin or allyl isothiocyanate (AITC) led to a stronger neurodegeneration. The use of TRPV1 blocker 6-iodo-nordihydrocapsaicin did not affect WIN-mediated neuroprotection. The selective Ca(v) 2.2 blocker ω-conotoxin (GVIA) completely blocked neuroprotection shown by 10 μM WIN. GVIA and HC-030031 exerted no effects at WIN concentrations lower than 10 μM. Our data show that WIN protects dentate gyrus granule cells in a concentration dependent manner by acting upon CB(1) receptors. At high (10 μM) concentrations WIN additionally activates TRPA1 and Ca(v) 2.2 within the hippocampal formation that both interfere with CB(1) receptor-mediated neuroprotection. This leads to the conclusion that physiological and pharmacological effects of cannabinoids strongly depend on their concentration and the neuroprotective efficacy of cannabinoids may be determined by interaction of activated CB(1) receptor, TRPA1, and Ca(v) 2.2.

Authors+Show Affiliations

Institut für Anatomie II, Goethe Universität Frankfurt am Main, Germany.No 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, Non-U.S. Gov't

Language

eng

PubMed ID

20135626

Citation

Koch, Marco, et al. "The Cannabinoid WIN 55,212-2-mediated Protection of Dentate Gyrus Granule Cells Is Driven By CB1 Receptors and Modulated By TRPA1 and Cav 2.2 Channels." Hippocampus, vol. 21, no. 5, 2011, pp. 554-64.
Koch M, Kreutz S, Böttger C, et al. The cannabinoid WIN 55,212-2-mediated protection of dentate gyrus granule cells is driven by CB1 receptors and modulated by TRPA1 and Cav 2.2 channels. Hippocampus. 2011;21(5):554-64.
Koch, M., Kreutz, S., Böttger, C., Grabiec, U., Ghadban, C., Korf, H. W., & Dehghani, F. (2011). The cannabinoid WIN 55,212-2-mediated protection of dentate gyrus granule cells is driven by CB1 receptors and modulated by TRPA1 and Cav 2.2 channels. Hippocampus, 21(5), 554-64. https://doi.org/10.1002/hipo.20772
Koch M, et al. The Cannabinoid WIN 55,212-2-mediated Protection of Dentate Gyrus Granule Cells Is Driven By CB1 Receptors and Modulated By TRPA1 and Cav 2.2 Channels. Hippocampus. 2011;21(5):554-64. PubMed PMID: 20135626.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The cannabinoid WIN 55,212-2-mediated protection of dentate gyrus granule cells is driven by CB1 receptors and modulated by TRPA1 and Cav 2.2 channels. AU - Koch,Marco, AU - Kreutz,Susanne, AU - Böttger,Charlotte, AU - Grabiec,Urszula, AU - Ghadban,Chalid, AU - Korf,Horst-Werner, AU - Dehghani,Faramarz, PY - 2010/2/6/entrez PY - 2010/2/6/pubmed PY - 2012/3/27/medline SP - 554 EP - 64 JF - Hippocampus JO - Hippocampus VL - 21 IS - 5 N2 - Cannabinoids regulate numerous physiological and pathological events like inflammation or neurodegeneration via CB(1) and CB(2) receptors. The mechanisms behind cannabinoid effects show a high variability and may also involve transient receptor potential channels (TRP) and N-type voltage-gated Ca(2+) channels (Ca(v) 2.2). In the present study we investigated the neuroprotective effects of the synthetic cannabinoid WIN 55,212-2 (WIN) on dentate gyrus (DG) granule cells and elucidated the involvement of TRP and Ca(v) 2.2 that are shown to participate in inflammatory processes. Organotypic hippocampal slice cultures were excitotoxically lesioned using NMDA and subsequently incubated with different WIN concentrations (0.001-10 μM). WIN showed neuroprotective properties in an inverse concentration-dependent manner, most effectively at 0.01 μM. The CB(1) receptor antagonist AM251 blocked neuroprotection mediated by WIN whereas the CB(2) receptor antagonist AM630 showed no effects. Application of the TRPA1 blocker HC-030031 enhanced the neuroprotective efficacy of high (10 μM) WIN concentrations and the number of degenerating neurons became equal to that seen after application of the most effective WIN dose (0.01 μM). In contrast, the application of TRPA1 agonist icilin or allyl isothiocyanate (AITC) led to a stronger neurodegeneration. The use of TRPV1 blocker 6-iodo-nordihydrocapsaicin did not affect WIN-mediated neuroprotection. The selective Ca(v) 2.2 blocker ω-conotoxin (GVIA) completely blocked neuroprotection shown by 10 μM WIN. GVIA and HC-030031 exerted no effects at WIN concentrations lower than 10 μM. Our data show that WIN protects dentate gyrus granule cells in a concentration dependent manner by acting upon CB(1) receptors. At high (10 μM) concentrations WIN additionally activates TRPA1 and Ca(v) 2.2 within the hippocampal formation that both interfere with CB(1) receptor-mediated neuroprotection. This leads to the conclusion that physiological and pharmacological effects of cannabinoids strongly depend on their concentration and the neuroprotective efficacy of cannabinoids may be determined by interaction of activated CB(1) receptor, TRPA1, and Ca(v) 2.2. SN - 1098-1063 UR - https://www.unboundmedicine.com/medline/citation/20135626/The_cannabinoid_WIN_55212_2_mediated_protection_of_dentate_gyrus_granule_cells_is_driven_by_CB1_receptors_and_modulated_by_TRPA1_and_Cav_2_2_channels_ L2 - https://doi.org/10.1002/hipo.20772 DB - PRIME DP - Unbound Medicine ER -