CB1 receptor

• CB1受容体、CB1カンナビノイド受容体、カンナビノイド1受容体、CB1レセプター

関

CB1 cannabinoid receptor

WordNet

1. the 3rd letter of the Roman alphabet (同)c
2. (music) the keynote of the scale of C major
3. a general-purpose programing language closely associated with the UNIX operating system
4. a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

PrepTutorEJDIC

1. carbonの化学記号
2. =sense organ / 受信装置
3. citizens band / construction battalion設営大隊

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/22 14:56:15」(JST)

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Cannabinoid receptor 1 (brain)
Rendering of CNR1 from PDB 1LVQ
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1LVQ, 1LVR, 2B0Y, 2KOE
Identifiers
Symbols	CNR1 ; CANN6; CB-R; CB1; CB1A; CB1K5; CB1R; CNR
External IDs	OMIM: 114610 MGI: 104615 HomoloGene: 7273 IUPHAR: 56 ChEMBL: 218 GeneCards: CNR1 Gene
Gene ontology Molecular function • cannabinoid receptor activity • drug binding Cellular component • plasma membrane • integral component of plasma membrane • axon • growth cone • intracellular membrane-bounded organelle • membrane raft Biological process • positive regulation of acute inflammatory response to antigenic stimulus • G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger • adenylate cyclase-modulating G-protein coupled receptor signaling pathway • spermatogenesis • axonal fasciculation • aging • response to nutrient • memory • positive regulation of neuron projection development • sensory perception of pain • positive regulation of fever generation • negative regulation of fatty acid beta-oxidation • regulation of synaptic transmission, GABAergic • response to lipopolysaccharide • negative regulation of mast cell activation • negative regulation of dopamine secretion • response to nicotine • cannabinoid signaling pathway • response to cocaine • glucose homeostasis • positive regulation of apoptotic process • response to morphine • response to ethanol • negative regulation of action potential • negative regulation of blood pressure • positive regulation of blood pressure • regulation of insulin secretion • negative regulation of nitric-oxide synthase activity • regulation of synaptic transmission, glutamatergic • maternal process involved in female pregnancy • regulation of feeding behavior • regulation of penile erection Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1268	12801
Ensembl	ENSG00000118432	ENSMUSG00000044288
UniProt	P21554	P47746
RefSeq (mRNA)	NM_001160226	NM_007726
RefSeq (protein)	NP_001153698	NP_031752
Location (UCSC)	Chr 6: 88.14 – 88.17 Mb	Chr 4: 33.92 – 33.95 Mb
PubMed search	[1]	[2]

The cannabinoid receptor type 1, often abbreviated as CB₁, is a G protein-coupled cannabinoid receptor located primarily in the central and peripheral nervous system. It is activated by the endocannabinoid neurotransmitters anandamide and 2-arachidonoylglycerol (2-AG); by plant cannabinoids, such as the compound THC, an active ingredient of the psychoactive drug cannabis; and by synthetic analogues of THC.

Structure

The CB₁ receptor shares the structure characteristic of all G-protein-coupled receptors, possessing seven transmembrane domains connected by three extracellular and three intracellular loops, an extracellular N-terminal tail, and an intracellular C-terminal tail. These receptors may exist as homodimers or form heterodimers or other GPCR oligomers when coexpressed with one or more classes of G-protein-coupled receptors. Observed heterodimers include A_2A–CB₁, CB₁–D₂, OX₁–CB₁, while many more may only be stable enough to exist in vivo. Recent evidence suggests that these receptors may also possess an allosteric binding site, which may become a target for enhancing the clinical modulatory effects of cannabinoids.

Mechanism

The CB₁ receptor is a pre-synaptic heteroreceptor that modulates neurotransmitter release when activated in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. The CB₁ receptor is activated by cannabinoids, generated naturally inside the body (endocannabinoids) or introduced into the body as cannabis or a related synthetic compound.

Research suggests that the majority of CB₁ receptors are coupled through G_i/o proteins. Upon activation, CB₁ receptor exhibits its effects mainly through activation of G_i, which decreases intracellular cAMP concentration by inhibiting its production enzyme, adenylate cyclase, and increases mitogen-activated protein kinase (MAP kinase) concentration. Alternatively, in some rare cases CB₁ receptor activation may be coupled to G_s proteins, which stimulate adenylate cyclase. cAMP is known to serve as a second messenger coupled to a variety of ion channels, including the positively influenced inwardly rectifying potassium channels (=Kir or IRK), and calcium channels, which are activated by cAMP-dependent interaction with such molecules as protein kinase A (PKA), protein kinase C (PKC), Raf-1, ERK, JNK, p38, c-fos, c-jun, and others. In terms of function, the inhibition of intracellular cAMP expression shortens the duration of pre-synaptic action potentials by prolonging the rectifying potassium A-type currents, which is normally inactivated upon phosphorylation by PKA. This inhibition grows more pronounced when considered with the effect of activated CB₁ receptors to limit calcium entry into the cell, which does not occur through cAMP but by a direct G-protein-mediated inhibition. As presynaptic calcium entry is a requirement for vesicle release, this function will decrease the transmitter that enters the synapse upon release. The relative contribution of each of these two inhibitory mechanisms depends on the variance of ion channel expression by cell type.

The CB₁ receptor can also be modulated by allosterically synthetic ligands in a positive and negative manner. In vivo exposure to THC impairs long-term potentiation and leads to a reduction of phosphorylated CREB.

In summary, CB₁ receptor activity has been found to be coupled to certain ion channels, in the following manner:

• Positively to inwardly rectifying and A-type outward potassium channels.
• Negatively to D-type outward potassium channels
• Negatively to N-type and P/Q-type calcium channels.

Expression

The CB₁ receptor is encoded by the gene CNR1, located on human chromosome 6. Two transcript variants encoding different isoforms have been described for this gene. CNR1 orthologs have been identified in most mammals.

The CB₁ receptor is expressed pre-synaptically at both glutaminergic and GABAergic interneurons and, in effect, acts as a neuromodulator to inhibit release of glutamate and GABA. Repeated administration of receptor agonists may result in receptor internalization and/ or a reduction in receptor protein signalling.

The inverse agonist MK-9470 makes it possible to produce in vivo images of the distribution of CB₁ receptors in the human brain with positron emission tomography.

Brain

Cnr1 is widely expressed in all major regions of the postnatal day 14 mouse brain, but is conspicuously absent in much of the thalamus. Allen Brain Atlases

CB₁ receptors are expressed most densely in the central nervous system and are largely responsible for mediating the effects of cannabinoid binding in the brain. Endocannabinoids released by a depolarized neuron bind to CB₁ receptors on either pre-synaptic glutamatergic or GABAergic neurons, resulting in a respective decrease in either glutamate or GABA release. Limiting glutamate release causes reduced excitation, while limiting GABA release suppresses inhibition, a common form of short-term plasticity in which the depolarization of a single neuron induces a reduction in GABA-mediated inhibition, in effect exciting the postsynaptic cell.

Varying levels of CB₁ expression can be detected in the olfactory bulb, cortical regions (neocortex, pyriform cortex, hippocampus, and amygdala), several parts of basal ganglia, thalamic and hypothalamic nuclei, and other subcortical regions (e.g., the septal region), cerebellar cortex, and brainstem nuclei (e.g., the periaqueductal gray).

Hippocampal formation

CB₁ mRNA transcripts are abundant in GABAergic interneurons of the hippocampus, indirectly reflecting the expression of these receptors and elucidating the established effect of cannabinoids on memory. These receptors are densely located in cornu ammonis pyramidal cells, which are known to release glutamate. Cannabinoids suppress the induction of LTP and LTD in the hippocampus by inhibiting these glutamatergic neurons. By reducing the concentration of glutamate released below the threshold necessary to depolarize the postynaptic receptor NMDA, a receptor known to be directly related to the induction of LTP and LTD, cannabinoids are a crucial factor in the selectivity of memory. These receptors are highly expressed by GABAergic interneurons as well as glutamatergic principal neurons. However, a higher density is found within GABAergic cells. This means that, although synaptic strength/frequency, and thus potential to induce LTP, is lowered, net hippocampal activity is raised. In addition, CB₁ receptors in the hippocampus indirectly inhibit the release of acetylcholine. This serves as the modulatory axis opposing GABA, decreasing neurotransmitter release. An undetermined complex fractal-based, feedforward network allows the brain to weaken specific synapses while others are enhanced, allowing long-range structure to be formed. Cannabinoids also likely play an important role in the development of memory through their neonatal promotion of myelin formation, and thus the individual segregation of axons.

Basal ganglia

CB₁ receptors are expressed throughout the basal ganglia and have well-established effects on movement in rodents. As in the hippocampus, these receptors inhibit the release of glutamate or GABA transmitter, resulting in decreased excitation or reduced inhibition based on the cell they are expressed in. Consistent with the variable expression of both excitatory glutamate and inhibitory GABA interneurons in both the basal ganglia's direct and indirect motor loops, synthetic cannabinoids are known to influence this system in a dose-dependent triphasic pattern. Decreased locomotor activity is seen at both higher and lower concentrations of applied cannabinoids, whereas an enhancement of movement may occur upon moderate dosages. However, these dose-dependent effects have been studied predominately in rodents, and the physiological basis for this triphasic pattern warrants future research in humans. Effects may vary based on the site of cannabinoid application, input from higher cortical centers, and whether drug application is unilateral or bilateral.

Cerebellum and neocortex

The role of the CB₁ receptor in the regulation of motor movements is complicated by the additional expression of this receptor in the cerebellum and neocortex, two regions associated with the coordination and initiation of movement. Research suggests that anandamide is synthesized by Purkinje cells and acts on presynaptic receptors to inhibit glutamate release from granule cells or GABA release from the terminals of basket cells. In the neocortex, these receptors are concentrated on local interneurons in cerebral layers II-III and V-VI. Compared to rat brains, humans express more CB₁ receptors in the cerebral cortex and amygdala and less in the cerebellum, which may help explain why motor function seems to be more compromised in rats than humans upon cannabinoid application.

Spine

Many of the documented analgesic effects of cannabinoids are based on the interaction of these compounds with CB₁ receptors on spinal cord interneurons in the superficial levels of the dorsal horn, known for its role in nociceptive processing. In particular, the CB₁ is heavily expressed in layers 1 and 2 of the spinal cord dorsal horn and in lamina 10 by the central canal. Dorsal root ganglion also express these receptors, which target a variety of peripheral terminals involved in nociception. Signals on this track are also transmitted to the periaqueductal gray (PAG) of the midbrain. Endogenous cannabinoids are believed to exhibit an analgesic effect on these receptors by limiting both GABA and glutamate of PAG cells that relate to nociceptive input processing, a hypothesis consistent with the finding that anandamide release in the PAG is increased in response to pain-triggering stimuli.

Other

CB₁ is expressed on several types of cell in pituitary gland, thyroid gland, and possibly in the adrenal gland. CB₁ is also expressed in several cells relating to metabolism, such as fat cells, muscle cells, liver cells (and also in the endothelial cells, Kupffer cells and stellate cells of the liver), and in the digestive tract. These receptor also expressed in the lungs and the kidney.

CB₁ is present on Leydig cells and human sperms. In females, it is present in the ovaries, oviducts myometrium, decidua, and placenta. It has also been implicated in the proper development of the embryo.

Function

Health and disease

Several studies have implicated the CB₁ receptor in the maintenance of homeostasis in health and disease. In a rodent neuropathic pain model, increased expression of these receptors was seen in thalamic neurons, the spinal cord, and dorsal root ganglion. In addition, increased receptor expression has been found in human hepatocellular carcinoma tumor samples and other human prostate cancer cells. The expression of these receptors is believed to modulate neurotransmitter release in a manner that prevents the development of excessive neuronal activity, reducing pain and other inflammatory symptoms. This finding is consistent with the localization of CB₁ receptors to the terminals of central and peripheral neurons, and the established mediation of both excitatory and inhibitory neurotransmitters acetylcholine, noradrenaline, dopamine, 5-HT, GABA, glutamate, D-aspartate, and cholecystokinin. Through its primary action as a G_i coupled receptor, CB1 inhibits production of cyclic adenosine monophosphate (cAMP), metabotropically inhibiting all NT release.

Enhanced receptor expression following disease has been found to result in a leftward shift in the log dose-response curve of cannabinol, and also an increase in the size of its maximal effects.

Anxiety response to novelty

A CB₁ receptor knock-out mouse study examined the effect that these receptors play on exploratory behavior in novel situations. Researchers selectively targeted glutamatergic and GABAergic cortical interneurons and studied results in open field, novel object, and sociability tests. Eliminating glutamaterigic cannabinoid receptors led to decreased object exploration, social interactions, and increased aggressive behavior. In contrast, GABAergic cannabinoid receptor-knockout mice showed increased exploration of objects, socialization, and open field movement. These opposing effects reveal the importance of the endocannabinoid system in regulating anxiety-dependent behavior. Glutamatergic CB₁receptors not only are responsible for mediating aggression but produce anxiolytic-like function by inhibiting excessive arousal, which prevented the mice from exploring both animate and inanimate objects. In contrast, GABAergic CB₁ receptors appear to control an anxiogenic-like function by limiting inhibitory transmitter release. Taken together, these results illustrate the regulatory function of the CB₁ receptor on the organism's overall sense of arousal during novel situations and suggest that investigatory drive is associated with impulsive behavior.

Another study found that differential synthesis of anandamide and 2-AG in response to stress mediated beneficial effects of the hypothalamic-pituitary-adrenal axis. These effects were eliminated by the application of the CB₁ antagonist AM251, illustrating that this receptor is essential for modulating the function of the stress response.

Liver

In the liver, activation of the CB₁ receptor is known to increase de novo lipogenesis, Activation of presynaptic CB₁ receptors is also known to inhibit sympathetic innervation of blood vessels and contributes to the suppression of the neurogenic vasopressor response in septic shock.

Gastrointestinal activity

Inhibition of gastrointestinal activity has been observed after administration of THC or anandamide. This effect is assumed to be CB₁-mediated, since this receptor is expressed by the peptide hormone cholecystokinin, and application of the CB₁-specific antagonist SR 141716A (Rimonabant) blocks the effect. Another report, however, suggests that inhibition of intestinal motility may also have a CB₂-mediated component.

The CB₁ receptor inverse agonist rimonabant has been found to reduce intake of food or sweet solutions in both humans and mice. Targeting this receptor with rimonabant has been found to prevent the THC-induced enhancement of DA release in the nucleus accumbens shell from food, suggesting that these receptors may be involved in determining the hedonic value of food. In addition, CB1 inhibits ghrelin release, normally happening when the stomach is stretched. In the presence of a relatively active system, overeating is promoted. This is the genesis of its appetite-stimulating effects, colloquially called "the munchies."

Cardiovascular activity

Cannabinoids are well known for their cardiovascular activity. Activation of peripheral CB1 receptors contributes to hemorrhagic and endotoxin-induced hypotension. Anandamide and 2-AG, produced by macrophages and platelets, respectively, may mediate this effect. A likely candidate for this function is the heterodimer of CB1 and adenosine 2a. Through an opposing mechanism of action (A2A elevates cAMP), together, they may serve to regulate cardiac blood supply, and thus output.

Plasticity

CB1 induction of LTD and STD have been shown in the Dorsal striatum, Amygdala, Prefrontal cortex, Ventral tegmental area, and the BNST. A recent study compared the endocannabinoid induction of LTD and STD in the bed nucleus of the stria terminalis (BNST) and striatum. Results found that both short- and long-term effects were dependent on CB₁ receptor activation in the striatum, whereas LTD induction in the BNST relied on TRPV1 receptor. Effects vary based on the endocannabinoid molecule: 2-AG was found to act on presynaptic CB₁ receptors to mediate retrograde short-term depression following activation of L-type calcium currents, whereas anandamide was synthesized after mGluR5 activation and triggered autocrine signalling that induced long-term depression. These findings demonstrate the CB₁ receptor as a direct mechanism for the brain to selectively inhibit neuronal excitability over variable time scales. By selectively internalizing different receptors, the brain may limit the production of specific endocannabinoids to favor a time scale in accordance with its needs. mGlu5 forms a heterodimer with A2A, which allows endocannabinoids to regulate their own levels, as they inhibit cAMP production, thus increase free adenosine to agonise A2A. This forms a feedback loop between the positive and negative metabotropic receptors, which can maintain a relatively similar homeostasis with any neuron connected through an electrical synapse.

Motor control

CB₁ receptors are expressed throughout motor regions of the mammalian brain, suggesting that CB₁ has a role in motor control. CB₁ activation has been shown to effect specific kinematic variables in rodents, such as the rate of applied force during lever pressing, and the amplitude (but not timing) of whisker movements.

Drug and behavioral addictions

Several recent reviews on CB1 receptors and addiction have indicated that CB1 receptor activation reinstates drug seeking behavior in addicts. In humans, this results from the influence that limbic CB1 receptors have on mesolimbic dopamine neurons, specifically dopamine receptors in the nucleus accumbens. As a consequence, CB1 receptor antagonists can reduce drug seeking behavior in some addicts.

Olfaction

The CB₁ receptor is expressed by a number of neurons that project from the anterior olfactory nucleus to the ipsilateral main olfactory bulb. However, the effects of cannabinoids on synaptic activity in these neurons has not been well-studied and its effects on olfaction warrant further research in rodents. Cannabinoids are not known to have effects on olfaction in humans. However, as with the rest of the brain, it plays a crucial role in modulation of NT release.

Use of antagonists

Selective CB₁ agonists may be used to isolate the effects of the receptor from the CB₂ receptor, as most cannabinoids and endocannabinoids bind to both receptor types. CB₁ selective antagonists are used for weight reduction and smoking cessation (see Rimonabant). A substantial number of antagonists of the CB1 receptor have been discovered and characterized. TM38837 has been developed as a CB1 receptor antagonist that is restricted to targeting only peripheral CB1 receptors.

Ligands

Agonists

Selective

• Epigallocatechin
• Epicatechin
• Kavain
• Yangonin

Unspecified efficacy

• N-Arachidonoyl dopamine
• Cannabinol
• HU-210
• 11-Hydroxy-THC
• Levonantradol

Inverse

• Rimonabant
• Taranabant

Partial

Endogenous

• 2-Arachidonyl glyceryl ether

Phyto/Synthetic

• JWH-073
• Tetrahydrocannabinol

Full

Endogenous

• 2-Arachidonoylglycerol

Phyto/Synthetic

• AM-2201
• CP 55,940
• JWH-018
• WIN 55,212-2

Antagonists

• Cannabigerol
• Ibipinabant
• Otenabant
• Tetrahydrocannabivarin
• Virodhamine (Endogenous CB1 antagonist and CB2 agonist)
• Cannabidiol

Binding affinities

	CB1 affinity (Ki)	Efficacy towards CB1	CB2 affinity (Ki)	Efficacy towards CB2	Type	References
Anandamide	78 nM	Full agonist	370 nM	Partial agonist	Endogenous
N-Arachidonoyl dopamine	250 nM	Agonist	12000 nM	?	Endogenous
2-Arachidonoylglycerol	58.3 nM	Full agonist	145 nM	Full agonist	Endogenous
2-Arachidonyl glyceryl ether	21 nM	Full agonist	480 nM	Full agonist	Endogenous
Tetrahydrocannabinol	10 nM	Partial agonist	24 nM	Partial agonist	Phytogenic
EGCG	33.6 μM	Agonist	>50 μM	?	Phytogenic
AM-1221	52.3 nM	Agonist	0.28 nM	Agonist	Synthetic
AM-1235	1.5 nM	Agonist	20.4 nM	Agonist	Synthetic
AM-2232	0.28 nM	Agonist	1.48 nM	Agonist	Synthetic
UR-144	150 nM	Full agonist	1.8 nM	Full agonist	Synthetic
JWH-007	9.0 nM	Agonist	2.94 nM	Agonist	Synthetic
JWH-015	383 nM	Agonist	13.8 nM	Agonist	Synthetic
JWH-018	9.00 ± 5.00 nM	Full agonist	2.94 ± 2.65 nM	Full agonist	Synthetic

Evolution

The CNR1 gene is used in animals as a nuclear DNA phylogenetic marker. This intronless gene has first been used to explore the phylogeny of the major groups of mammals, and contributed to reveal that placental orders are distributed into five major clades: Xenarthra, Afrotheria, Laurasiatheria, Euarchonta, and Glires. CNR1 has also proven useful at lower taxonomic levels, such as rodents, and for the identification of dermopterans as the closest primate relatives.

See also

• Discovery and development of Cannabinoid Receptor 1 Antagonists
• Cannabinoid receptor
• Cannabinoid receptor type 2 (CB₂)

References

External links

• "Cannabinoid Receptors: CB₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 

Further reading

• Gérard CM, Mollereau C, Vassart G, Parmentier M (Oct 1991). "Molecular cloning of a human cannabinoid receptor which is also expressed in testis". The Biochemical Journal. 279 ( Pt 1) (1): 129–34. PMC 1151556. PMID 1718258. 
• Hoehe MR, Caenazzo L, Martinez MM, Hsieh WT, Modi WS, Gershon ES, Bonner TI (Sep 1991). "Genetic and physical mapping of the human cannabinoid receptor gene to chromosome 6q14-q15". The New Biologist 3 (9): 880–5. PMID 1931832. 
• Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (Aug 1990). "Structure of a cannabinoid receptor and functional expression of the cloned cDNA". Nature 346 (6284): 561–4. Bibcode:1990Natur.346..561M. doi:10.1038/346561a0. PMID 2165569. 
• Gérard C, Mollereau C, Vassart G, Parmentier M (Dec 1990). "Nucleotide sequence of a human cannabinoid receptor cDNA". Nucleic Acids Research 18 (23): 7142. doi:10.1093/nar/18.23.7142. PMC 332788. PMID 2263478. 
• Shire D, Carillon C, Kaghad M, Calandra B, Rinaldi-Carmona M, Le Fur G, Caput D, Ferrara P (Feb 1995). "An amino-terminal variant of the central cannabinoid receptor resulting from alternative splicing". The Journal of Biological Chemistry 270 (8): 3726–31. doi:10.1074/jbc.270.8.3726. PMID 7876112. 
• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
• Kenney SP, Kekuda R, Prasad PD, Leibach FH, Devoe LD, Ganapathy V (Aug 1999). "Cannabinoid receptors and their role in the regulation of the serotonin transporter in human placenta". American Journal of Obstetrics and Gynecology 181 (2): 491–7. doi:10.1016/S0002-9378(99)70583-1. PMID 10454705. 
• Porcella A, Maxia C, Gessa GL, Pani L (Mar 2000). "The human eye expresses high levels of CB1 cannabinoid receptor mRNA and protein". The European Journal of Neuroscience 12 (3): 1123–7. doi:10.1046/j.1460-9568.2000.01027.x. PMID 10762343. 
• Mukhopadhyay S, Howlett AC (Feb 2001). "CB1 receptor-G protein association. Subtype selectivity is determined by distinct intracellular domains". European Journal of Biochemistry / FEBS 268 (3): 499–505. doi:10.1046/j.1432-1327.2001.01810.x. PMID 11168387. 
• Murphy WJ, Eizirik E, Johnson WE, Zhang YP, Ryder OA, O'Brien SJ (Feb 2001). "Molecular phylogenetics and the origins of placental mammals". Nature 409 (6820): 614–8. doi:10.1038/35054550. PMID 11214319. 
• Nong L, Newton C, Friedman H, Klein TW (2002). "CB1 and CB2 receptor mRNA expression in human peripheral blood mononuclear cells (PBMC) from various donor types". Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology 493: 229–33. doi:10.1007/0-306-47611-8_27. ISBN 0-306-46466-7. PMID 11727770. 
• Leroy S, Griffon N, Bourdel MC, Olié JP, Poirier MF, Krebs MO (Dec 2001). "Schizophrenia and the cannabinoid receptor type 1 (CB1): association study using a single-base polymorphism in coding exon 1". American Journal of Medical Genetics 105 (8): 749–52. doi:10.1002/ajmg.10038. PMID 11803524. 
• Schmidt LG, Samochowiec J, Finckh U, Fiszer-Piosik E, Horodnicki J, Wendel B, Rommelspacher H, Hoehe MR (Feb 2002). "Association of a CB1 cannabinoid receptor gene (CNR1) polymorphism with severe alcohol dependence". Drug and Alcohol Dependence 65 (3): 221–4. doi:10.1016/S0376-8716(01)00164-8. PMID 11841893. 
• Lastres-Becker I, Cebeira M, de Ceballos ML, Zeng BY, Jenner P, Ramos JA, Fernández-Ruiz JJ (Dec 2001). "Increased cannabinoid CB1 receptor binding and activation of GTP-binding proteins in the basal ganglia of patients with Parkinson's syndrome and of MPTP-treated marmosets". The European Journal of Neuroscience 14 (11): 1827–32. doi:10.1046/j.0953-816x.2001.01812.x. PMID 11860478. 
• Petrelli A, Gilestro GF, Lanzardo S, Comoglio PM, Migone N, Giordano S (Mar 2002). "The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met". Nature 416 (6877): 187–90. Bibcode:2002Natur.416..187P. doi:10.1038/416187a. PMID 11894096. 
• Huang SM, Bisogno T, Trevisani M, Al-Hayani A, De Petrocellis L, Fezza F, Tognetto M, Petros TJ, Krey JF, Chu CJ, Miller JD, Davies SN, Geppetti P, Walker JM, Di Marzo V (Jun 2002). "An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors". Proceedings of the National Academy of Sciences of the United States of America 99 (12): 8400–5. Bibcode:2002PNAS...99.8400H. doi:10.1073/pnas.122196999. PMC 123079. PMID 12060783. 
• Ujike H, Takaki M, Nakata K, Tanaka Y, Takeda T, Kodama M, Fujiwara Y, Sakai A, Kuroda S (2002). "CNR1, central cannabinoid receptor gene, associated with susceptibility to hebephrenic schizophrenia". Molecular Psychiatry 7 (5): 515–8. doi:10.1038/sj.mp.4001029. PMID 12082570. 
• Ho BY, Current L, Drewett JG (Jul 2002). "Role of intracellular loops of cannabinoid CB(1) receptor in functional interaction with G(alpha16)". FEBS Letters 522 (1-3): 130–4. doi:10.1016/S0014-5793(02)02917-4. PMID 12095632. 
• Matias I, Pochard P, Orlando P, Salzet M, Pestel J, Di Marzo V (Aug 2002). "Presence and regulation of the endocannabinoid system in human dendritic cells". European Journal of Biochemistry / FEBS 269 (15): 3771–8. doi:10.1046/j.1432-1033.2002.03078.x. PMID 12153574. 
• Oddi S, Spagnuolo P, Bari M, D'Agostino A, Maccarrone M (2007). "Differential modulation of type 1 and type 2 cannabinoid receptors along the neuroimmune axis". International Review of Neurobiology. International Review of Neurobiology 82: 327–37. doi:10.1016/S0074-7742(07)82017-4. ISBN 978-0-12-373989-6. PMID 17678969. 
• Flores-Otero J, Ahn KH, Delgado-Peraza F, Mackie K, Kendall DA, Yudowski GA (2014). "Ligand-specific endocytic dwell times control functional selectivity of the cannabinoid receptor 1". Nature Communications 5: 4589. Bibcode:2014NatCo...5E4589F. doi:10.1038/ncomms5589. PMID 25081814. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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• The journal of physiological sciences 65(5), 407-415, 2015-09
• NAID 40020576513

• 咽頭・喉頭感覚が関与する生理・薬理作用


• 日本薬理学雑誌 145(6), 278-282, 2015
• NAID 130005075724

• Endocannabinoid-mediated retrograde modulation of synaptic transmission

• Current Opinion in Neurobiology 29, 1-8, 2014-12
• NAID 120005435504

Related Links

• Cannabinoid receptor - Wikipedia, the free encyclopedia

NMR solution structure of a peptide mimetic of the fourth cytoplasmic loop of the CB1 cannabinoid receptor based on the PDB 2b0y .... Activation of peripheral CB1 receptors contributes to hemorrhagic and endotoxin-induced hypotension.

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★リンクテーブル★

リンク元	「CB1カンナビノイド受容体」「CB1受容体」「CB1レセプター」「カンナビノイド1受容体」「CB1 cannabinoid receptor」
関連記事	「C」「CB」

「CB1カンナビノイド受容体」

　　[★]

英

CB1 cannabinoid receptor、CB1 receptor

関

CB1カンナビノイドレセプター、CB1受容体、CB1レセプター、カンナビノイド1受容体

「CB1受容体」

　　[★]

英

CB1 receptor

関

CB1カンナビノイド受容体、CB1レセプター、カンナビノイド1受容体

「CB1レセプター」

　　[★]

英

CB1 receptor

関

CB1カンナビノイド受容体、CB1受容体、カンナビノイド1受容体

「カンナビノイド1受容体」

　　[★]

英

CB1 receptor

関

CB1カンナビノイド受容体、CB1受容体、CB1レセプター

「CB1 cannabinoid receptor」

　　[★]

CB1カンナビノイド受容体、CB1カンナビノイドレセプター

関

CB1 receptor

「C」

　　[★]

• 炭素 carbon
• シトシン cytosine
• システイン cysteine
• シチジン
• セルシウス度 摂氏 degrees Celsius degree C
• 産婦人科領域で「子宮外頚 子宮外頚部 exocervix」を表現するための略語

　 　 　 　

「CB」

　　[★] 慢性気管支炎 chronic bronchitis