Abstract
Cannabinoids have widespread effects on the cardiovascular system, only some of which are mediated via G-protein-coupled cell surface receptors. The active ingredient of cannabis, {delta}{sup 9}-tetrahydrocannabinol (THC), causes acute vasorelaxation in various arteries. Here we show for the first time that THC also causes slowly developing vasorelaxation through activation of peroxisome proliferator-activated receptors gamma (PPAR{gamma}). In vitro, THC (10 {mu}M) caused time-dependent vasorelaxation of rat isolated arteries. Time-dependent vasorelaxation to THC was similar to that produced by the PPAR{gamma} agonist rosiglitazone and was inhibited by the PPAR{gamma} antagonist GW9662 (1 {mu}M), but not the cannabinoid CB{sub 1} receptor antagonist AM251 (1 {mu}M). Time-dependent vasorelaxation to THC requires an intact endothelium, nitric oxide, production of hydrogen peroxide, and de novo protein synthesis. In transactivation assays in cultured HEK293 cells, THC-activated PPAR{gamma}, transiently expressed in combination with retinoid X receptor {alpha} and a luciferase reporter gene, in a concentration-dependent manner (100 nM-10 {mu}M). In vitro incubation with THC (1 or 10 {mu}M, 8 days) stimulated adipocyte differentiation in cultured 3T3L1 cells, a well-accepted property of PPAR{gamma} ligands. The present results provide strong evidence that THC is a PPAR{gamma} ligand, stimulation of which causes time-dependent vasorelaxation, implying some of the pleiotropic effects of
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O'Sullivan, Saoirse E;
[1]
Tarling, Elizabeth J;
[1]
Bennett, Andrew J;
[1]
Kendall, David A;
[1]
Randall, Michael D
[1]
- School of Biomedical Sciences, E Floor, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom)
Citation Formats
O'Sullivan, Saoirse E, Tarling, Elizabeth J, Bennett, Andrew J, Kendall, David A, and Randall, Michael D.
Novel time-dependent vascular actions of {delta}{sup 9}-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma.
United States: N. p.,
2005.
Web.
doi:10.1016/j.bbrc.2005.09.121.
O'Sullivan, Saoirse E, Tarling, Elizabeth J, Bennett, Andrew J, Kendall, David A, & Randall, Michael D.
Novel time-dependent vascular actions of {delta}{sup 9}-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma.
United States.
https://doi.org/10.1016/j.bbrc.2005.09.121
O'Sullivan, Saoirse E, Tarling, Elizabeth J, Bennett, Andrew J, Kendall, David A, and Randall, Michael D.
2005.
"Novel time-dependent vascular actions of {delta}{sup 9}-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma."
United States.
https://doi.org/10.1016/j.bbrc.2005.09.121.
@misc{etde_20713453,
title = {Novel time-dependent vascular actions of {delta}{sup 9}-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma}
author = {O'Sullivan, Saoirse E, Tarling, Elizabeth J, Bennett, Andrew J, Kendall, David A, and Randall, Michael D}
abstractNote = {Cannabinoids have widespread effects on the cardiovascular system, only some of which are mediated via G-protein-coupled cell surface receptors. The active ingredient of cannabis, {delta}{sup 9}-tetrahydrocannabinol (THC), causes acute vasorelaxation in various arteries. Here we show for the first time that THC also causes slowly developing vasorelaxation through activation of peroxisome proliferator-activated receptors gamma (PPAR{gamma}). In vitro, THC (10 {mu}M) caused time-dependent vasorelaxation of rat isolated arteries. Time-dependent vasorelaxation to THC was similar to that produced by the PPAR{gamma} agonist rosiglitazone and was inhibited by the PPAR{gamma} antagonist GW9662 (1 {mu}M), but not the cannabinoid CB{sub 1} receptor antagonist AM251 (1 {mu}M). Time-dependent vasorelaxation to THC requires an intact endothelium, nitric oxide, production of hydrogen peroxide, and de novo protein synthesis. In transactivation assays in cultured HEK293 cells, THC-activated PPAR{gamma}, transiently expressed in combination with retinoid X receptor {alpha} and a luciferase reporter gene, in a concentration-dependent manner (100 nM-10 {mu}M). In vitro incubation with THC (1 or 10 {mu}M, 8 days) stimulated adipocyte differentiation in cultured 3T3L1 cells, a well-accepted property of PPAR{gamma} ligands. The present results provide strong evidence that THC is a PPAR{gamma} ligand, stimulation of which causes time-dependent vasorelaxation, implying some of the pleiotropic effects of cannabis may be mediated by nuclear receptors.}
doi = {10.1016/j.bbrc.2005.09.121}
journal = []
issue = {3}
volume = {337}
place = {United States}
year = {2005}
month = {Nov}
}
title = {Novel time-dependent vascular actions of {delta}{sup 9}-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma}
author = {O'Sullivan, Saoirse E, Tarling, Elizabeth J, Bennett, Andrew J, Kendall, David A, and Randall, Michael D}
abstractNote = {Cannabinoids have widespread effects on the cardiovascular system, only some of which are mediated via G-protein-coupled cell surface receptors. The active ingredient of cannabis, {delta}{sup 9}-tetrahydrocannabinol (THC), causes acute vasorelaxation in various arteries. Here we show for the first time that THC also causes slowly developing vasorelaxation through activation of peroxisome proliferator-activated receptors gamma (PPAR{gamma}). In vitro, THC (10 {mu}M) caused time-dependent vasorelaxation of rat isolated arteries. Time-dependent vasorelaxation to THC was similar to that produced by the PPAR{gamma} agonist rosiglitazone and was inhibited by the PPAR{gamma} antagonist GW9662 (1 {mu}M), but not the cannabinoid CB{sub 1} receptor antagonist AM251 (1 {mu}M). Time-dependent vasorelaxation to THC requires an intact endothelium, nitric oxide, production of hydrogen peroxide, and de novo protein synthesis. In transactivation assays in cultured HEK293 cells, THC-activated PPAR{gamma}, transiently expressed in combination with retinoid X receptor {alpha} and a luciferase reporter gene, in a concentration-dependent manner (100 nM-10 {mu}M). In vitro incubation with THC (1 or 10 {mu}M, 8 days) stimulated adipocyte differentiation in cultured 3T3L1 cells, a well-accepted property of PPAR{gamma} ligands. The present results provide strong evidence that THC is a PPAR{gamma} ligand, stimulation of which causes time-dependent vasorelaxation, implying some of the pleiotropic effects of cannabis may be mediated by nuclear receptors.}
doi = {10.1016/j.bbrc.2005.09.121}
journal = []
issue = {3}
volume = {337}
place = {United States}
year = {2005}
month = {Nov}
}