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CB1 receptor

Family: Cannabinoid receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Biologically Significant Variants
General Comments
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 472 6q14-q15 CNR1 cannabinoid receptor 1 (brain) 18,24
Mouse 7 473 4 A5 Cnr1 cannabinoid receptor 1 (brain) 5
Rat 7 473 5q21 Cnr1 cannabinoid receptor 1 (brain) 37
Previous and Unofficial Names
Cannabinoid receptor
Brain-type cannabinoid receptor
Central cannabinoid receptor
Neuronal cannabinoid receptor
THC receptors
CNR
CB1K5
CB-R
CB1
CANN6
CB1A
SKR6R
cannabinoid receptor 1
cannabinoid receptor 1 (brain)
CB1R
Database Links
ChEMBL Target
DrugBank Target
Ensembl
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProt
Wikipedia
Search for 3D structures on the PDB
Search by keyword: Cannabinoid receptors CB1 receptor
Natural/Endogenous Ligand(s)
2-arachidonoylglycerol
anandamide
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]HU-243 Rn Full agonist 10.4 pKd 8
[3H]CP55940 Hs Full agonist 8.5 – 9.4 pKd 2-3,13,17,48,51
[3H]WIN55212-2 Hs Full agonist 7.8 – 7.9 pKd 7,53
HU-210 Hs Full agonist 9.1 – 10.2 pKi 12,51
arachidonyl-2-chloroethylamide Rn Full agonist 8.8 pKi 22
CP55940 Hs Full agonist 8.3 – 9.2 pKi 12,47,51
arachidonyl cyclopropylamide Rn Full agonist 8.7 pKi 22
O-1812 Rn Full agonist 8.5 pKi 9
WIN55212-2 Hs Full agonist 6.9 – 8.7 pKi 12,49,51
R-(+)-methanandamide Rn Agonist 7.7 pKi 29
Δ9-tetrahydrocannabinol Hs Partial agonist 7.3 – 7.4 pKi 12,51
2-arachidonoylglycerol Rn Full agonist 6.3 – 7.2 pKi 1,38
anandamide Hs Partial agonist 6.3 – 7.0 pKi 12,51
cannabinol Hs Partial agonist 6.0 – 6.5 pKi 12,51
View species-specific agonist tables
Agonist Comments
The higher pKi value of anandamide (7.05) was determined in the presence of phenylmethylsulfonyl fluoride to prevent enzymic hydrolysis. For reviews see references [25,40-41]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[123I]AM251 Mm Antagonist 9.6 pKd 15
[3H]rimonabant Rn Antagonist 8.9 – 9.7 pKd 4,23,28,42,45-46,52,55
AM251 Rn Antagonist 8.1 pKi 31
rimonabant Hs Antagonist 7.9 – 8.2 pKi 11-12,44,51
AM281 Rn Antagonist 7.9 pKi 30
LY320135 Hs Antagonist 6.8 pKi 11
View species-specific antagonist tables

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Potassium channel
Calcium channel
Other - See Comments
Comments:  Activation of MAP kinase leading to immediate early gene expression[25]
References:  2,6,14,16,20,26,33-34,39,54,58
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  19,43
Tissue Distribution
Primarily CNS and some peripheral neurones; particularly prevalent in basal ganglia, hippocampus, cerebellum, cerebral cortex. Also present in some non-neuronal cells and tissues, for example leukocytes and testis.
Species:  Human
Technique:  Radioligand binding
References:  21,25,35,40
Primarily CNS and innervation to tissues by peripheral nervous system; particularly prevalent in basal ganglia, hippocampus, cerebellum, cerebral cortex.
Species:  Rat
Technique:  Radioligand binding
References:  21,27,56
Expression Datasets

Click here to show/hide data

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Nerve-smooth muscle tissue preparation
Species:  Mouse
Tissue:  Vas deferens
Response measured:  Inhibition of electrically-evoked contractions
References:  25,40
Drug discrimination (also primates and pigeons)
Species:  Rat
Tissue:  In vivo
Response measured:  Drug discrimination
References:  25
Tetrad of hypothermia, antinociception, hypoactivity and catalepsy
Species:  Rat
Tissue:  In vivo
Response measured:  Rectal temperature, tail flick or hot plate response, spontaneous locomotor activity and ring immobility, all measured in the same animal.
References:  25,36,59
Tetrad of hypothermia, antinociception, hypoactivity and catalepsy
Species:  Mouse
Tissue:  In vivo
Response measured:  Rectal temperature, tail flick or hot plate response, spontaneous locomotor activity and ring immobility, all measured in the same animal.
References:  25,36,59
Physiological Functions
Modulation of neurotransmitter release
Species:  Rat
Tissue:  Brain, spinal cord and some peripheral tissues
References:  25
Modulation of neurotransmitter release
Species:  Mouse
Tissue:  Brain and some peripheral tissues
References:  25
Physiological Consequences of Altering Gene Expression
CB1 knockout mice bred on a C57BL/6J background show hypoactivity, reduced locomotion and rearing, hypoalgesia, hypophagia, changed male hormone balance and increased mortality. CB1 knockout mice bred on a CD1 background show increased locomotor and exploratory activity when newly exposed to an arena but no change in nociception or mortality. Neither of these mouse lines respond to CB1 receptor agonists in CB1 assays, one notable exception being the antinociceptive response to Δ9-THC that is exhibited in the tail flick test by CB1 knockout mice with the C57/BL/6J background. CB1 knockout mice respond less than wild-type mice to the reinforcing properties of opioids.
Species:  Mouse
Tissue: 
Technique:  Induced mutation.
References:  32,60
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cnr1tm1.2Ltz|Tg(dlx6a-cre)1Mekk Cnr1tm1.2Ltz/Cnr1tm1.2Ltz,Tg(dlx6a-cre)1Mekk/?
involves: 129P2/OlaHsd
MGI:104615  MGI:3758078  MP:0000788 abnormal cerebral cortex morphology PMID: 17525344 
Cnr1tm1Ojm Cnr1tm1Ojm/Cnr1tm1Ojm
involves: 129P2/OlaHsd * C57BL/6
MGI:104615  MP:0002912 abnormal excitatory postsynaptic potential PMID: 12060781 
Cnr1tm1Ojm Cnr1tm1Ojm/Cnr1tm1Ojm
involves: 129P2/OlaHsd * C57BL/6
MGI:104615  MP:0005449 abnormal food intake PMID: 14770190 
Cnr1tm1.2Ltz|Tg(dlx6a-cre)1Mekk Cnr1tm1.2Ltz/Cnr1tm1.2Ltz,Tg(dlx6a-cre)1Mekk/?
involves: 129P2/OlaHsd * C57BL/6NCrl
MGI:104615  MGI:3758078  MP:0002945 abnormal inhibitory postsynaptic currents PMID: 16908411 
Cnr1tm1.1Ltz Cnr1tm1.1Ltz/Cnr1tm1.1Ltz
B6.129P2-Cnr1
MGI:104615  MP:0002063 abnormal learning/memory/conditioning PMID: 12152079 
Cnr1tm1Map Cnr1tm1Map/Cnr1tm1Map
involves: 129S1/Sv * 129X1/SvJ * CD-1
MGI:104615  MP:0004948 abnormal neuronal precursor proliferation PMID: 15266010 
Cnr1tm1.1Ltz Cnr1tm1.1Ltz/Cnr1tm1.1Ltz
B6.129P2-Cnr1
MGI:104615  MP:0002918 abnormal paired-pulse facilitation PMID: 12152079 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0002907 abnormal parturition PMID: 18833324 
Cnr1tm1Zim|Ptgs1tm1Unc Cnr1tm1Zim/Cnr1tm1Zim,Ptgs1tm1Unc/Ptgs1tm1Unc
involves: 129/Sv * 129P2/OlaHsd * C57BL/6J
MGI:104615  MGI:97797  MP:0002907 abnormal parturition PMID: 18833324 
Cnr1tm1Map Cnr1tm1Map/Cnr1tm1Map
involves: 129S1/Sv * 129X1/SvJ * CD-1
MGI:104615  MP:0003461 abnormal response to novel object PMID: 9888857 
Cnr1tm1Ojm Cnr1tm1Ojm/Cnr1tm1Ojm
involves: 129P2/OlaHsd * C57BL/6
MGI:104615  MP:0001899 absent long term depression PMID: 12060781 
Cnr1tm1.1Ltz Cnr1tm1.1Ltz/Cnr1tm1.1Ltz
B6.129P2-Cnr1
MGI:104615  MP:0001899 absent long term depression PMID: 12152079 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0002822 catalepsy PMID: 10318961 
Cnr1tm1Ojm Cnr1tm1Ojm/Cnr1tm1Ojm
involves: 129P2/OlaHsd * C57BL/6
MGI:104615  MP:0001262 decreased body weight PMID: 14770190 
Cnr1tm1Map Cnr1tm1Map/Cnr1tm1Map
involves: 129S1/Sv * 129X1/SvJ * CD-1
MGI:104615  MP:0001982 decreased chemically-elicited antinociception PMID: 9888857 
Cnr1tm1Ojm Cnr1tm1Ojm/Cnr1tm1Ojm
involves: 129P2/OlaHsd * C57BL/6
MGI:104615  MP:0002727 decreased circulating insulin level PMID: 14770190 
Cnr1tm1Ojm Cnr1tm1Ojm/Cnr1tm1Ojm
involves: 129P2/OlaHsd * C57BL/6
MGI:104615  MP:0005668 decreased circulating leptin level PMID: 14770190 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0005185 decreased circulating progesterone level PMID: 18833324 
Cnr1tm1.1Ltz Cnr1tm1.1Ltz/Cnr1tm1.1Ltz
B6.129P2-Cnr1
MGI:104615  MP:0001417 decreased exploration in new environment PMID: 12152079 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0008770 decreased survivor rate PMID: 10318961 
Cnr1tm1Ojm Cnr1tm1Ojm/Cnr1tm1Ojm
involves: 129P2/OlaHsd * C57BL/6
MGI:104615  MP:0010025 decreased total body fat amount PMID: 14770190 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0002757 decreased vertical activity PMID: 10318962 
Cnr1tm1.1Ltz Cnr1tm1.1Ltz/Cnr1tm1.1Ltz
B6.129P2-Cnr1
MGI:104615  MP:0003008 enhanced long term potentiation PMID: 12152079 
Cnr1tm1Map Cnr1tm1Map/Cnr1tm1Map
involves: 129S1/Sv * 129X1/SvJ * CD-1
MGI:104615  MP:0001399 hyperactivity PMID: 9888857 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0001402 hypoactivity PMID: 10318961  10318962 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0003043 hypoalgesia PMID: 10318961 
Cnr1tm1Map Cnr1tm1Map/Cnr1tm1Map
involves: 129S1/Sv * 129X1/SvJ * CD-1
MGI:104615  MP:0009750 impaired behavioral response to addictive substance PMID: 9888857 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0009750 impaired behavioral response to addictive substance PMID: 10318961 
Cnr1tm1Map Cnr1tm1Map/Cnr1tm1Map
involves: 129S1/Sv * 129X1/SvJ * CD-1
MGI:104615  MP:0009757 impaired behavioral response to morphine PMID: 9888857 
Cnr1tm1Dgen Cnr1tm1Dgen/Cnr1tm1Dgen
involves: 129S1/Sv * 129X1/SvJ
MGI:104615  MP:0009747 impaired behavioral response to xenobiotic PMID: 12917492 
Cnr1tm1Map Cnr1tm1Map/Cnr1tm1Map
involves: 129S1/Sv * 129X1/SvJ * CD-1
MGI:104615  MP:0009712 impaired conditioned place preference behavior PMID: 9888857 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0008531 increased chemical nociceptive threshold PMID: 10318961 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0001745 increased circulating corticosterone level PMID: 18833324 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0005182 increased circulating estradiol level PMID: 18833324 
Cnr1tm1Map Cnr1tm1Map/Cnr1tm1Map
involves: 129S1/Sv * 129X1/SvJ * CD-1
MGI:104615  MP:0001415 increased exploration in new environment PMID: 9888857 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0005131 increased follicle stimulating hormone level PMID: 18833324 
Cnr1tm1Ojm Cnr1tm1Ojm/Cnr1tm1Ojm
involves: 129P2/OlaHsd * C57BL/6
MGI:104615  MP:0002891 increased insulin sensitivity PMID: 14770190 
Cnr1tm1Ojm Cnr1tm1Ojm/Cnr1tm1Ojm
involves: 129P2/OlaHsd * C57BL/6
MGI:104615  MP:0005659 increased resistance to diet-induced obesity PMID: 14770190 
Cnr1tm1.1Ltz Cnr1tm1.1Ltz/Cnr1tm1.1Ltz
involves: 129P2/OlaHsd * C57BL/6N
MGI:104615  MP:0009766 increased sensitivity to xenobiotic induced morbidity/mortality PMID: 14526074 
Cnr1tm1.2Ltz|Tg(Camk2a-cre)2Gsc Cnr1tm1.2Ltz/Cnr1tm1.2Ltz,Tg(Camk2a-cre)2Gsc/0
involves: 129P2/OlaHsd * C57BL/6N
MGI:104615  MGI:2181425  MP:0009766 increased sensitivity to xenobiotic induced morbidity/mortality PMID: 14526074 
Cnr1tm1.2Ltz|Tg(Camk2a-cre)2Gsc Cnr1tm1.2Ltz/Cnr1tm1.2Ltz,Tg(Camk2a-cre)2Gsc/0
involves: 129P2/OlaHsd * C57BL/6N
MGI:104615  MGI:2181425  MP:0008235 increased susceptibility to neuronal excitotoxicity PMID: 14526074 
Cnr1tm1.1Ltz Cnr1tm1.1Ltz/Cnr1tm1.1Ltz
involves: 129P2/OlaHsd * C57BL/6N
MGI:104615  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 14526074 
Cnr1+|Cnr1tm1.1Ltz Cnr1tm1.1Ltz/Cnr1+
involves: 129P2/OlaHsd * C57BL/6N
MGI:104615  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 14526074 
Cnr1tm1.2Ltz|Tg(Camk2a-cre)2Gsc Cnr1tm1.2Ltz/Cnr1tm1.2Ltz,Tg(Camk2a-cre)2Gsc/0
involves: 129P2/OlaHsd * C57BL/6N
MGI:104615  MGI:2181425  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 14526074 
Cnr1tm1.2Ltz|Tg(Camk2a-cre)2Gsc Cnr1tm1.2Ltz/Cnr1tm1.2Ltz,Tg(Camk2a-cre)2Gsc/?
involves: 129P2/OlaHsd * C57BL/6NCrl * FVB/N
MGI:104615  MGI:2181425  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 16908411 
Cnr1tm1.2Ltz Cnr1tm1.2Ltz/Cnr1tm1.2Ltz
involves: 129P2/OlaHsd * C57BL/6NCrl
MGI:104615  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 16908411 
Cnr1tm1.2Ltz|Neurod6+|Neurod6tm1(cre)Kan Cnr1tm1.2Ltz/Cnr1tm1.2Ltz,Neurod6tm1(cre)Kan/Neurod6+
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6NCrl
MGI:104615  MGI:106593  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 16908411 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0001973 increased thermal nociceptive threshold PMID: 10318961 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0003718 maternal effect PMID: 18833324 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0002082 postnatal lethality PMID: 10318961 
Cnr1tm1Zim Cnr1tm1Zim/Cnr1tm1Zim
involves: 129/Sv * C57BL/6J
MGI:104615  MP:0002083 premature death PMID: 10318961 
Cnr1tm1Dgen Cnr1tm1Dgen/Cnr1tm1Dgen
involves: 129S1/Sv * 129X1/SvJ * ICR
MGI:104615  MP:0001475 reduced long term depression PMID: 18256258 
Cnr1tm1Ojm Cnr1tm1Ojm/Cnr1tm1Ojm
involves: 129P2/OlaHsd * C57BL/6
MGI:104615  MP:0001263 weight loss PMID: 14770190 
Biologically Significant Variants
A shorter human splice variant (411aa) has been identified in the brain and other tissues by reverse-transcriptase PCR but mRNA levels were less than 10-fold the levels of the longer isoform. It is unlikely to exist in mouse or rat due to an altered splice donor site. The pharmacological characteristics of the isoforms are similar. CB1 receptor knock-out mice are now available to clarify receptor-mediated responses.
Type:  Splice variants.
Species:  Human
References:  25,50
General Comments
Techniques used include in situ hybridization and immunohistochemistry[10,57]

REFERENCES

To cite this database page, please use the following:

Mary Abood, Francis Barth, Tom I. Bonner, Guy Cabral, Pierre Casellas, Ben F. Cravatt, William A. Devane, Maurice R. Elphick, Christian C. Felder, Miles Herkenham, Allyn C. Howlett, George Kunos, Ken Mackie, Billy R. Martin, Raphael Mechoulam, Roger G. Pertwee.
Cannabinoid receptors: CB1 receptor. Last modified on 03/12/2012. Accessed on 24/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=56.


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