Academic Journal
Involvement of TRPV1 channels in the activity of the cannabinoid WIN 55,212-2 in an acute rat model of temporal lobe epilepsy
| العنوان: | Involvement of TRPV1 channels in the activity of the cannabinoid WIN 55,212-2 in an acute rat model of temporal lobe epilepsy |
|---|---|
| المؤلفون: | CARLETTI, Fabio, Gambino, Giuditta, RIZZO, Valerio, FERRARO, Giuseppe, SARDO, Pierangelo |
| المساهمون: | Carletti, F, Gambino, G, Rizzo, V, Ferraro, G, Sardo, P |
| بيانات النشر: | ELSEVIER SCIENCE BV |
| سنة النشر: | 2016 |
| المجموعة: | IRIS Università degli Studi di Palermo |
| مصطلحات موضوعية: | Hippocampus, Temporal lobe epilepsy, Cannabinoids, TRPV1, Capsaicin, Electrophysiology, Settore BIO/09 - Fisiologia |
| الوصف: | 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 themodulation of transient receptor potential vanilloid 1 (TRPV1), a cationic channel subfamily that regulate synaptic excitation. In our study, we assessed the influence of pharmacological manipulationof 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 10 mg/kg is able to reduce its antiepileptic strength, especially on the triggering of MDA response. Accordingly, capsazepine at the protective dose of 2 mg/kg managed to potentiate WIN antiepileptic effects, when co-treated. Moreover, WIN subeffective dose of 5 mg/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 TRPV1signaling that could represent a promising approach for a future pharmacological strategy to challenge hyperexcitability-based diseases. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/26970948; info:eu-repo/semantics/altIdentifier/wos/WOS:000374805100009; volume:122; firstpage:56; lastpage:65; numberofpages:10; journal:EPILEPSY RESEARCH; http://hdl.handle.net/10447/176153; http://www.ncbi.nlm.nih.gov/pubmed/26970948 |
| DOI: | 10.1016/j.eplepsyres.2016.02.005 |
| الاتاحة: | http://hdl.handle.net/10447/176153 https://doi.org/10.1016/j.eplepsyres.2016.02.005 http://www.ncbi.nlm.nih.gov/pubmed/26970948 |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.65F3556B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.eplepsyres.2016.02.005 |
|---|