Author Interviews, Cannabis, Nature, UT Southwestern, Weight Research / 19.11.2016
Precise Structure of Cannabis Brain Receptor Defined
MedicalResearch.com Interview with:
[caption id="attachment_29787" align="alignleft" width="300"]
(l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum UT Southwestern[/caption]
Dan Rosenbaum, Ph.D.
Principal Investigator
Department of Biophysics
The University of Texas Southwestern Medical Center
Dallas, Texas
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This study focuses on the structure of the human CB1 cannabinoid receptor.
The CB1 protein is a membrane-embedded G protein-coupled receptor (GPCR) in the brain and peripheral tissues that responds to a variety of different compounds, including endogenous lipid messengers (‘endocannabinoids’), plant natural products (such as THC from the Cannabis sativa plant i.e. marijuana), and synthetic antagonists (such as the taranabant ligand used for this study). The CB1 receptor is involved in regulating neurotransmission in vertebrates, and is a potential therapeutic target for numerous conditions including obesity, pain, and epilepsy.
The main findings of this study entailed the solution of the high-resolution crystal structure of human CB1 receptor bound to the inhibitor taranabant. This structure revealed the precise shape of the inhibitor binding pocket, which is also responsible for binding THC and endocannabinoids. In addition to helping explain the mechanism of inhibitor and THC binding, our structure provides a framework for computational studies of binding to a large diversity of cannabinoid modulators of therapeutic importance.
(l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum UT Southwestern[/caption]
Dan Rosenbaum, Ph.D.
Principal Investigator
Department of Biophysics
The University of Texas Southwestern Medical Center
Dallas, Texas
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This study focuses on the structure of the human CB1 cannabinoid receptor.
The CB1 protein is a membrane-embedded G protein-coupled receptor (GPCR) in the brain and peripheral tissues that responds to a variety of different compounds, including endogenous lipid messengers (‘endocannabinoids’), plant natural products (such as THC from the Cannabis sativa plant i.e. marijuana), and synthetic antagonists (such as the taranabant ligand used for this study). The CB1 receptor is involved in regulating neurotransmission in vertebrates, and is a potential therapeutic target for numerous conditions including obesity, pain, and epilepsy.
The main findings of this study entailed the solution of the high-resolution crystal structure of human CB1 receptor bound to the inhibitor taranabant. This structure revealed the precise shape of the inhibitor binding pocket, which is also responsible for binding THC and endocannabinoids. In addition to helping explain the mechanism of inhibitor and THC binding, our structure provides a framework for computational studies of binding to a large diversity of cannabinoid modulators of therapeutic importance.





















