Document Detail

Cannabinoid receptor 1 in the vagus nerve is dispensable for body weight homeostasis but required for normal gastrointestinal motility.
MedLine Citation:
PMID:  22836266     Owner:  NLM     Status:  MEDLINE    
The cannabinoid receptor 1 (CB(1)R) is required for body weight homeostasis and normal gastrointestinal motility. However, the specific cell types expressing CB(1)R that regulate these physiological functions are unknown. CB(1)R is widely expressed, including in neurons of the parasympathetic branches of the autonomic nervous system. The vagus nerve has been implicated in the regulation of several aspects of metabolism and energy balance (e.g., food intake and glucose balance), and gastrointestinal functions including motility. To directly test the relevance of CB(1)R in neurons of the vagus nerve on metabolic homeostasis and gastrointestinal motility, we generated and characterized mice lacking CB(1)R in afferent and efferent branches of the vagus nerve (Cnr1(flox/flox); Phox2b-Cre mice). On a chow or on a high-fat diet, Cnr1(flox/flox); Phox2b-Cre mice have similar body weight, food intake, energy expenditure, and glycemia compared with Cnr1(flox/flox) control mice. Also, fasting-induced hyperphagia and after acute or chronic pharmacological treatment with SR141716 [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole carboxamide] (CB(1)R inverse agonist) paradigms, mutants display normal body weight and food intake. Interestingly, Cnr1(flox/flox); Phox2b-Cre mice have increased gastrointestinal motility compared with controls. These results unveil CB(1)R in the vagus nerve as a key component underlying normal gastrointestinal motility.
Claudia R Vianna; Jose Donato; Jari Rossi; Michael Scott; Kyriakos Economides; Lauren Gautron; Stephanie Pierpont; Carol F Elias; Joel K Elmquist
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  32     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-27     Completed Date:  2012-10-29     Revised Date:  2014-10-22    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10331-7     Citation Subset:  IM    
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MeSH Terms
Body Weight / drug effects,  genetics*
Diet, High-Fat
Eating / drug effects,  genetics
Food Deprivation
Gastrointestinal Motility / drug effects,  genetics*
Homeostasis / drug effects,  genetics*
Hyperphagia / genetics,  metabolism
Mice, Transgenic
Piperidines / pharmacology
Pyrazoles / pharmacology
Receptor, Cannabinoid, CB1 / antagonists & inhibitors,  genetics,  metabolism*
Vagus Nerve / metabolism*
Grant Support
Reg. No./Substance:
0/Cnr1 protein, rat; 0/Piperidines; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1; 158681-13-1/rimonabant

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