Tags

Type your tag names separated by a space and hit enter

R-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphtalenylmethanone (WIN-2) ameliorates experimental autoimmune encephalomyelitis and induces encephalitogenic T cell apoptosis: partial involvement of the CB(2) receptor.
Biochem Pharmacol 2006; 72(12):1697-706BP

Abstract

Many reports have shown that cannabinoids might be beneficial in the symptomatic treatment of multiple sclerosis (MS). We have investigated the therapeutic properties of the non-selective cannabinoid receptor agonist WIN-2 as a suppressive drug in the experimental autoimmune encephalomyelitis (EAE) model of MS. In the passive variety of EAE, induced in Lewis rats by adoptive transfer of myelin-reactive T cells, WIN-2 ameliorates the clinical signs and diminishes the cell infiltration of the spinal cord. Due to the involvement of cannabinoids in the regulation of cell death and survival, we investigated the effects of WIN-2 on the encephalitogenic T cell population. WIN-2 induced a profound increase of apoptosis in a dose- and time-dependent manner. The potential involvement of cannabinoid receptors (CB) was investigated by encephalitogenic T cell stimulation in the presence of the CB(1) (SR141716A) and CB(2) (SR144528) antagonists, pertussis toxin (PTX) and the inactive enantiomer WIN-3. WIN-2-induced apoptosis was partially blocked by SR144528 and PTX, whereas, WIN-3 only exerted a mild effect on cell viability. These results point to the partial involvement of CB(2) receptor together with other receptor-independent mechanism or by yet unknown cannabinoid receptors. Moreover, WIN-2 induced the extrinsic pathway of apoptosis, as shown by caspase-10 and -3 activation. These results suggest that cannabinoid-induced apoptosis of encephalitogenic T cells may cooperate in their anti-inflammatory action in EAE models. The partial involvement of CB(2) receptors in WIN-2 action may open new therapeutic doors in the management of MS by non-psychoactive selective cannabinoid agonists.

Authors+Show Affiliations

Neuroimmunology Unit, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, San Martin de Porres 4, 28035 Madrid, Spain.No 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

17007821

Citation

Sánchez, Antonio J., et al. "R-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphtalenylmethanone (WIN-2) Ameliorates Experimental Autoimmune Encephalomyelitis and Induces Encephalitogenic T Cell Apoptosis: Partial Involvement of the CB(2) Receptor." Biochemical Pharmacology, vol. 72, no. 12, 2006, pp. 1697-706.
Sánchez AJ, González-Pérez P, Galve-Roperh I, et al. R-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphtalenylmethanone (WIN-2) ameliorates experimental autoimmune encephalomyelitis and induces encephalitogenic T cell apoptosis: partial involvement of the CB(2) receptor. Biochem Pharmacol. 2006;72(12):1697-706.
Sánchez, A. J., González-Pérez, P., Galve-Roperh, I., & García-Merino, A. (2006). R-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphtalenylmethanone (WIN-2) ameliorates experimental autoimmune encephalomyelitis and induces encephalitogenic T cell apoptosis: partial involvement of the CB(2) receptor. Biochemical Pharmacology, 72(12), pp. 1697-706.
Sánchez AJ, et al. R-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphtalenylmethanone (WIN-2) Ameliorates Experimental Autoimmune Encephalomyelitis and Induces Encephalitogenic T Cell Apoptosis: Partial Involvement of the CB(2) Receptor. Biochem Pharmacol. 2006 Dec 15;72(12):1697-706. PubMed PMID: 17007821.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - R-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphtalenylmethanone (WIN-2) ameliorates experimental autoimmune encephalomyelitis and induces encephalitogenic T cell apoptosis: partial involvement of the CB(2) receptor. AU - Sánchez,Antonio J, AU - González-Pérez,Paz, AU - Galve-Roperh,Ismael, AU - García-Merino,Antonio, Y1 - 2006/08/26/ PY - 2006/07/07/received PY - 2006/08/08/revised PY - 2006/08/21/accepted PY - 2006/9/30/pubmed PY - 2007/1/31/medline PY - 2006/9/30/entrez SP - 1697 EP - 706 JF - Biochemical pharmacology JO - Biochem. Pharmacol. VL - 72 IS - 12 N2 - Many reports have shown that cannabinoids might be beneficial in the symptomatic treatment of multiple sclerosis (MS). We have investigated the therapeutic properties of the non-selective cannabinoid receptor agonist WIN-2 as a suppressive drug in the experimental autoimmune encephalomyelitis (EAE) model of MS. In the passive variety of EAE, induced in Lewis rats by adoptive transfer of myelin-reactive T cells, WIN-2 ameliorates the clinical signs and diminishes the cell infiltration of the spinal cord. Due to the involvement of cannabinoids in the regulation of cell death and survival, we investigated the effects of WIN-2 on the encephalitogenic T cell population. WIN-2 induced a profound increase of apoptosis in a dose- and time-dependent manner. The potential involvement of cannabinoid receptors (CB) was investigated by encephalitogenic T cell stimulation in the presence of the CB(1) (SR141716A) and CB(2) (SR144528) antagonists, pertussis toxin (PTX) and the inactive enantiomer WIN-3. WIN-2-induced apoptosis was partially blocked by SR144528 and PTX, whereas, WIN-3 only exerted a mild effect on cell viability. These results point to the partial involvement of CB(2) receptor together with other receptor-independent mechanism or by yet unknown cannabinoid receptors. Moreover, WIN-2 induced the extrinsic pathway of apoptosis, as shown by caspase-10 and -3 activation. These results suggest that cannabinoid-induced apoptosis of encephalitogenic T cells may cooperate in their anti-inflammatory action in EAE models. The partial involvement of CB(2) receptors in WIN-2 action may open new therapeutic doors in the management of MS by non-psychoactive selective cannabinoid agonists. SN - 0006-2952 UR - https://www.unboundmedicine.com/medline/citation/17007821/R__+__[23_Dihydro_5_methyl_3__4_morpholinylmethyl__pyrrolo_[123_de]_14_benzoxazin_6_yl]_1_naphtalenylmethanone__WIN_2__ameliorates_experimental_autoimmune_encephalomyelitis_and_induces_encephalitogenic_T_cell_apoptosis:_partial_involvement_of_the_CB_2__receptor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(06)00530-2 DB - PRIME DP - Unbound Medicine ER -