Cannabinoid 1 (CB1) Receptor - Pharmacology, Role in Pain and Recent Developments in Emerging CB1 Agonists

Talwar, Rashmi; Potluri, Vijay

doi:10.2174/187152711796235005

Cited by 25 publications

(16 citation statements)

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“…The opposing roles of cannabinoid receptors and TRPV1 channels in pain are well established and have been reviewed in numerous articles (see, [94][95][96] for up-to-date examples). Recent evidence suggests, however, that one should move away from the 'old' concept that selective activation of CB1 or TRPV1 attenuate or worsen nociception, respectively.…”

Section: Anandamide Dual Actions At Cb1 and Trpv1 As A 'Plastic' Way mentioning

confidence: 99%

Why do cannabinoid receptors have more than one endogenous ligand?

Marzo

Petrocellis

2012

Phil. Trans. R. Soc. B

252

176

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The endocannabinoid system was revealed following the understanding of the mechanism of action of marijuana's major psychotropic principle, D 9-tetrahydrocannabinol, and includes two G-proteincoupled receptors (GPCRs; the cannabinoid CB1 and CB2 receptors), their endogenous ligands (the endocannabinoids, the best studied of which are anandamide and 2-arachidonoylglycerol (2-AG)), and the proteins that regulate the levels and activity of these receptors and ligands. However, other minor lipid metabolites different from, but chemically similar to, anandamide and 2-AG have also been suggested to act as endocannabinoids. Thus, unlike most other GPCRs, cannabinoid receptors appear to have more than one endogenous agonist, and it has been often wondered what could be the physiological meaning of this peculiarity. In 1999, it was proposed that anandamide might also activate other targets, and in particular the transient receptor potential of vanilloid type-1 (TRPV1) channels. Over the last decade, this interaction has been shown to occur both in peripheral tissues and brain, during both physiological and pathological conditions. TRPV1 channels can be activated also by another less abundant endocannabinoid, N-arachidonoyldopamine, but not by 2-AG, and have been proposed by some authors to act as ionotropic endocannabinoid receptors. This article will discuss the latest discoveries on this subject, and discuss, among others, how anandamide and 2-AG differential actions at TRPV1 and cannabinoid receptors contribute to making this signalling system a versatile tool available to organisms to fine-tune homeostasis.

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Section: Anandamide Dual Actions At Cb1 and Trpv1 As A 'Plastic' Way mentioning

confidence: 99%

Why do cannabinoid receptors have more than one endogenous ligand?

Marzo

Petrocellis

2012

Phil. Trans. R. Soc. B

252

176

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“…They activate specific G protein-coupled cannabinoid receptors, CB1 and CB2. CB1 cannabinoid receptors are present in both central and peripheral neurons and are thought to mediate most of the analgesic effects of cannabinoids [16, 24]. In experimental cystitis models, in which pain is largely NGF- and TRPV1-dependent [11, 13, 28], cannabinoids prevent inflammatory hyperalgesia via activation of CB1 receptors [9, 10].…”

Section: Introductionmentioning

confidence: 99%

CB1 cannabinoid receptor agonist prevents NGF-induced sensitization of TRPV1 in sensory neurons

McDowell

Wang

Singh

et al. 2013

Neuroscience Letters

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The transient receptor potential vanilloid type 1 channel (TRPV1) and nerve growth factor (NGF) are important mediators of inflammatory pain. NGF released during inflammation sensitizes TRPV1 in afferent nerve endings of peripheral nociceptors, increasing pain sensation. Cannabinoids, by activating CB1 G protein-coupled receptors, produce analgesia in a variety of pain models, though the exact mechanisms are not known. We tested the hypothesis that activation of the CB1 receptor by cannabinoids attenuates NGF-induced TRPV1 sensitization. TRPV1-mediated currents were measured in acutely isolated primary sensory neurons with the whole-cell patch clamp technique using capsaicin (100 nM) as the agonist. After the first capsaicin application, during which the baseline current was measured, cells were exposed to NGF (100 ng/mL), and the capsaicin application was repeated after 5 minutes. NGF sensitized TRPV1 in 31.0 % of cells (13 of 42), with a mean (± SE) increase in the capsaicin-induced current of 262 ± 47 % over the baseline current. When the cannabinoid agonist ACEA (arachidonoyl-2’-chloroethylamide; 10 nM) was given before NGF, only 10.8 % of cells (4 of 37) were sensitized (p < 0.05). Neither this rate, nor the magnitude of the sensitization (198 ± 63 % of baseline) were different from that seen in cells not treated with NGF (3 of 25 cells sensitized (12.0 %), 253 ± 70 % of baseline). Pretreatment with the CB1 antagonist AM-251 (100 nM) prevented the effect of ACEA on NGF-induced sensitization. These results support the hypothesis that cannabinoids, acting through CB1 receptors, may produce analgesia in part by preventing NGF-induced sensitization of TRPV1 in afferent nociceptor nerve endings.

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“…CB 1 is strongly expressed in a number of different regions of the central nervous system such as the hypothalamus, hippocampus, and dorsal root ganglia (DRG) where it is known to play a role in modulating appetite (3–5), cognition and memory (6–8), and inflammatory pain, respectively (9). …”

Section: Introductionmentioning

confidence: 99%

Allele-specific Differences in Activity of a Novel Cannabinoid Receptor 1 (CNR1) Gene Intronic Enhancer in Hypothalamus, Dorsal Root Ganglia, and Hippocampus

Nicoll

Davidson

Shanley

et al. 2012

Journal of Biological Chemistry

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Background: Intron 2 of CNR1 gene contains multiple disease-associated SNPs.Results: Allelic variants of a novel enhancer in CNR1 intron 2 affect its MAPK response in hypothalamus and hippocampus.Conclusion: Alleles of enhancer may be functionally linked to obesity and addictive behavior.Significance: Understanding the effects of CNR1 polymorphisms on gene regulation will accelerate understanding of human disease.

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Cannabinoid 1 (CB1) Receptor - Pharmacology, Role in Pain and Recent Developments in Emerging CB1 Agonists

Cited by 25 publications

References 0 publications

Why do cannabinoid receptors have more than one endogenous ligand?

Why do cannabinoid receptors have more than one endogenous ligand?

CB1 cannabinoid receptor agonist prevents NGF-induced sensitization of TRPV1 in sensory neurons

Allele-specific Differences in Activity of a Novel Cannabinoid Receptor 1 (CNR1) Gene Intronic Enhancer in Hypothalamus, Dorsal Root Ganglia, and Hippocampus

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