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Involvement of TRPV1 channels in the activity of the cannabinoid WIN 55,212-2 in an acute rat model of temporal lobe epilepsy.
Epilepsy Res. 2016 May; 122:56-65.ER

Abstract

The exogenous cannabinoid agonist WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN), has revealed to play a role on modulating the hyperexcitability phenomena in the hippocampus. Cannabinoid-mediated mechanisms of neuroprotection have recently been found to imply the modulation of transient receptor potential vanilloid 1 (TRPV1), a cationic channel subfamily that regulate synaptic excitation. In our study, we assessed the influence of pharmacological manipulation of TRPV1 function, alone and on WIN antiepileptic activity, in the Maximal Dentate Activation (MDA) acute model of temporal lobe epilepsy. Our results showed that the TRPV1 agonist, capsaicin, increased epileptic outcomes; whilst antagonizing TRPV1 with capsazepine exerts a protective role on paroxysmal discharge. When capsaicin is co-administered with WIN effective dose of 10mg/kg is able to reduce its antiepileptic strength, especially on the triggering of MDA response. Accordingly, capsazepine at the protective dose of 2mg/kg managed to potentiate WIN antiepileptic effects, when co-treated. Moreover, WIN subeffective dose of 5mg/kg was turned into effective when capsazepine comes into play. This evidence suggests that systemic administration of TRPV1-active drugs influences electrically induced epilepsy, with a noticeable protective activity for capsazepine. Furthermore, results from the pharmacological interaction with WIN support an interplay between cannabinoid and TRPV1 signaling that could represent a promising approach for a future pharmacological strategy to challenge hyperexcitability-based diseases.

Authors+Show Affiliations

Department of "Biomedicina Sperimentale e Neuroscienze Cliniche" (Bio.Ne.C.), "Sezione di Fisiologia umana G. Pagano", University of Palermo, Corso Tukory 129-90134 Palermo, Italy. Electronic address: fabio.carletti@unipa.it.Department of "Biomedicina Sperimentale e Neuroscienze Cliniche" (Bio.Ne.C.), "Sezione di Fisiologia umana G. Pagano", University of Palermo, Corso Tukory 129-90134 Palermo, Italy. Electronic address: giuditta.gambino@unipa.it.Department of "Biomedicina Sperimentale e Neuroscienze Cliniche" (Bio.Ne.C.), "Sezione di Fisiologia umana G. Pagano", University of Palermo, Corso Tukory 129-90134 Palermo, Italy. Electronic address: valerio.rizzo@unipa.it.Department of "Biomedicina Sperimentale e Neuroscienze Cliniche" (Bio.Ne.C.), "Sezione di Fisiologia umana G. Pagano", University of Palermo, Corso Tukory 129-90134 Palermo, Italy. Electronic address: giuseppe.ferraro@unipa.it.Department of "Biomedicina Sperimentale e Neuroscienze Cliniche" (Bio.Ne.C.), "Sezione di Fisiologia umana G. Pagano", University of Palermo, Corso Tukory 129-90134 Palermo, Italy. Electronic address: pierangelo.sardo@unipa.it.

Pub Type(s)

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

Language

eng

PubMed ID

26970948

Citation

Carletti, Fabio, et al. "Involvement of TRPV1 Channels in the Activity of the Cannabinoid WIN 55,212-2 in an Acute Rat Model of Temporal Lobe Epilepsy." Epilepsy Research, vol. 122, 2016, pp. 56-65.
Carletti F, Gambino G, Rizzo V, et al. Involvement of TRPV1 channels in the activity of the cannabinoid WIN 55,212-2 in an acute rat model of temporal lobe epilepsy. Epilepsy Res. 2016;122:56-65.
Carletti, F., Gambino, G., Rizzo, V., Ferraro, G., & Sardo, P. (2016). Involvement of TRPV1 channels in the activity of the cannabinoid WIN 55,212-2 in an acute rat model of temporal lobe epilepsy. Epilepsy Research, 122, 56-65. https://doi.org/10.1016/j.eplepsyres.2016.02.005
Carletti F, et al. Involvement of TRPV1 Channels in the Activity of the Cannabinoid WIN 55,212-2 in an Acute Rat Model of Temporal Lobe Epilepsy. Epilepsy Res. 2016;122:56-65. PubMed PMID: 26970948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of TRPV1 channels in the activity of the cannabinoid WIN 55,212-2 in an acute rat model of temporal lobe epilepsy. AU - Carletti,Fabio, AU - Gambino,Giuditta, AU - Rizzo,Valerio, AU - Ferraro,Giuseppe, AU - Sardo,Pierangelo, PY - 2015/09/28/received PY - 2016/01/18/revised PY - 2016/02/09/accepted PY - 2016/3/14/entrez PY - 2016/3/14/pubmed PY - 2016/12/28/medline KW - Cannabinoids KW - Capsaicin KW - Electrophysiology KW - Hippocampus KW - TRPV1 KW - Temporal lobe epilepsy SP - 56 EP - 65 JF - Epilepsy research JO - Epilepsy Res. VL - 122 N2 - The exogenous cannabinoid agonist WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN), has revealed to play a role on modulating the hyperexcitability phenomena in the hippocampus. Cannabinoid-mediated mechanisms of neuroprotection have recently been found to imply the modulation of transient receptor potential vanilloid 1 (TRPV1), a cationic channel subfamily that regulate synaptic excitation. In our study, we assessed the influence of pharmacological manipulation of TRPV1 function, alone and on WIN antiepileptic activity, in the Maximal Dentate Activation (MDA) acute model of temporal lobe epilepsy. Our results showed that the TRPV1 agonist, capsaicin, increased epileptic outcomes; whilst antagonizing TRPV1 with capsazepine exerts a protective role on paroxysmal discharge. When capsaicin is co-administered with WIN effective dose of 10mg/kg is able to reduce its antiepileptic strength, especially on the triggering of MDA response. Accordingly, capsazepine at the protective dose of 2mg/kg managed to potentiate WIN antiepileptic effects, when co-treated. Moreover, WIN subeffective dose of 5mg/kg was turned into effective when capsazepine comes into play. This evidence suggests that systemic administration of TRPV1-active drugs influences electrically induced epilepsy, with a noticeable protective activity for capsazepine. Furthermore, results from the pharmacological interaction with WIN support an interplay between cannabinoid and TRPV1 signaling that could represent a promising approach for a future pharmacological strategy to challenge hyperexcitability-based diseases. SN - 1872-6844 UR - https://www.unboundmedicine.com/medline/citation/26970948/Involvement_of_TRPV1_channels_in_the_activity_of_the_cannabinoid_WIN_55212_2_in_an_acute_rat_model_of_temporal_lobe_epilepsy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0920-1211(16)30016-X DB - PRIME DP - Unbound Medicine ER -