Disease relevance of Cnr1

• Selective cannabinoid CB1 receptor-mediated inhibition of inducible nitric oxide synthase protein expression in C6 rat glioma cells [1].
• The present study was designed to investigate the central (CB1) and the peripheral (CB2) cannabinoid receptor expression in neonatal cardiomyoctes and possible function in the cardioprotection of THC from hypoxia [2].
• These results indicate that cannabinoid receptor agonists may be effective agents for craniofacial pain [3].
• The selective CB1 antagonist, AM281 (0.5 microg/kg-1 i.p.) reversed effects of HU210 (10 and 30 microg/kg-1 i.p.) in both nociceptive and inflammatory models of hypersensitivity [4].
• BACKGROUND: Cannabinoid receptor agonists inhibit inflammatory hyperalgesia in animal models [5].

Psychiatry related information on Cnr1

• Potential role of the cannabinoid receptor CB1 in rapid eye movement sleep rebound [6].
• Unlike sleep deprivation, sleep rebound significantly increased CB1R protein while decreasing mRNA [7].
• The effects of the highest dose of AMG-3 on spontaneous activity and on the self-stimulation paradigm were completely reversed by pre-treatment with the CB1 receptor antagonist AM-251 [8].
• An acute dose (100 microg/kg) of the CB1 agonist HU-210 suppressed locomotor activity, and had an anxiogenic-like effect on the elevated plus-maze [9].
• The effects of chronic exposure to cannabinoids on short-term memory in rats were assessed during repeated daily injections of an initially debilitating dose (3.75 mg/kg) of the potent CB1 cannabinoid receptor ligand, WIN 55,212-2 [10].

High impact information on Cnr1

• CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression [11].
• Two endogenous lipids, anandamide and 2-arachidonylglycerol (2-AG), have been identified as CB1 ligands [12].
• A synthetic CB1 agonist depresses GABA release from hippocampal slices [12].
• In the hippocampus, CB1 is expressed mainly by GABA (gamma-aminobutyric acid)-mediated inhibitory interneurons, where CB1 clusters on the axon terminal [12].
• Other endogenous (2-arachidonylglycerol, palmitylethanolamide) and synthetic (HU 210, WIN 55,212-2, CP 55,940) CB1 and CB2 receptor agonists could not mimic the action of anandamide [13].

Chemical compound and disease context of Cnr1

• Results indicated that SR141716A prevents REM sleep rebound and REM sleep deprivation does not modify the expression of the CB1 protein or mRNA [6].
• CONCLUSIONS: We conclude that endocannabinoids tonically suppress cardiac contractility in hypertension and that enhancing the CB1-mediated cardiodepressor and vasodilator effects of endogenous anandamide by blocking its hydrolysis can normalize blood pressure [14].
• R(+)-WIN 55212-2 also protected cultured cerebral cortical neurons from in vitro hypoxia and glucose deprivation, but in contrast to the receptor-mediated neuroprotection observed in vivo, this in vitro effect was not stereoselective and was insensitive to CB1 and CB2 receptor antagonists [15].
• Both cannabinoid receptor agonists failed to affect the capsaicin-evoked bradycardia [16].
• Pertussis toxin treatment of CHO cells expressing the CB1 receptor attenuated the anandamide-mediated inhibition of adenylate cyclase and unmasked a stimulatory effect of anandamide on adenylate cyclase [17].

Biological context of Cnr1

• Evidence for an interaction between CB1 cannabinoid and melanocortin MCR-4 receptors in regulating food intake [18].
• Furthermore, the activation of CNR1 reduces sperm motility [19].
• However, these facts suggest that CB1R gene expression is modulated by the light/dark cycle and by sleep [7].
• Binding studies using the selective cannabinoid CB1 receptor antagonist, [3H]SR141716A, indicated the presence of the specific binding site [20].
• CB-1 receptor down-regulation is consistent with increased activation of these receptors by endogenous cannabinoids [21].

Anatomical context of Cnr1

• We have studied the effects of two cannabinoid receptor agonists, WIN 55,212-2 and cannabinol, on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in the C6 glioma cell line [1].
• These data suggest that selective cannabinoid CB1 receptor activation, by inhibiting iNOS expression and NO overproduction in glial cells, might be helpful in NO-mediated inflammation leading to neurodegeneration [1].
• Cellular coexistence of 5-HT3A and CB1 transcripts in interneurons of the cortex, hippocampal formation, and amygdala suggest possible interactions between the cannabinoid and serotonergic systems at the level of GABA neurotransmission in brain areas involved in cognition, memory, and emotion [22].
• Furthermore, very few neurons (approximately 5%) in the peptidergic (defined as calcitonin gene-related peptide- or substance P-immunoreactive) or the isolectin B4-binding sensory neuron populations contained CB1 mRNA [23].
• In vivo and in vitro treatment with the synthetic cannabinoid CP55, 940 decreases the in vitro migration of macrophages in the rat: involvement of both CB1 and CB2 receptors [24].

Associations of Cnr1 with chemical compounds

• The cannabinoid CB1 receptor antagonist, SR141716A (0.1-100 nM), but not the cannabinoid CB2 receptor antagonist, SR144528 (0.1-100 nM), reduced in a dose-related manner WIN 55,212-2-and cannabinol-induced inhibition of nitrite production [1].
• Cannabinoid CB1 receptor and serotonin 3 receptor subunit A (5-HT3A) are co-expressed in GABA neurons in the rat telencephalon [22].
• These results provide the first evidence indicating that the only ion channel receptor for serotonin and central CB1 cannabinoid receptor coexist in neurons containing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) [25].
• In the present study, the cannabinoid CB1/CB2 receptor agonist, WIN 55,212-2 (WIN), was bath applied to the brainstem while activity of spinal trigeminal nucleus caudalis (Vc) neurons evoked by transcutaneous electrical stimulation was recorded in isoflurane anesthetized rats [3].
• After expression in neuronal membranes of the cannabinoid CB1, glutamate mGluR2, or dopamine D1 receptor (by microinjection of the levant receptor's cDNA into the neuron's nucleus) agonists' and antagonists' effects were observed [26].

Physical interactions of Cnr1

• The CB(1) cannabinoid receptor was also shown to be coupled to the activation of p38 mitogen-activated protein kinase [27].
• The CB(1) cannabinoid receptor is coupled to the activation of c-Jun N-terminal kinase [27].
• The apparent binding affinity was markedly increased when the binding assay was carried out in the presence of the esterase inhibitor DFP or at 0 degrees C. Free arachidonic acid and N-palmitoylethanolamine were almost inactive in terms of binding to the cannabinoid receptor in synaptosomal membranes [28].

Regulatory relationships of Cnr1

• Semi-quantitative analysis demonstrated that, depending on the hippocampal layer, 72-88% of CB1-expressing interneurons coexpress the 5-HT3A subunit [25].
• Cannabinoid CB1 receptors in the brain are expressed on axon terminals presynaptic to neurons that express fatty acid amide hydrolase (FAAH) [29].
• Recent evidence indicates the existence of cannabinoid receptors distinct from CB1 or CB2 that are inhibited by SR-141716 but not by other CB1 antagonists such as AM251 [30].
• Data indicate that activation of JNK and p38 mitogen-activated protein kinase may be responsible for some of the cellular responses elicited by the CB(1) cannabinoid receptor [27].
• We conclude that the cellular and subcellular pattern of type 1 cannabinoid receptor expression during early post-natal life is similar to the adult pattern and type 1 cannabinoid receptors are expressed on the cholecystokinin-containing axons as soon as synapse formation begins [31].

Other interactions of Cnr1

• The pretreatment with the CB2 antagonist, but not with the CB1 antagonist, was able to prevent this effect [24].
• By using a combination of double in situ hybridization and immunohistochemistry, we demonstrated that 5-HT3A/CB1-expressing neurons contained the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) [22].
• Endocannabinoid system in frog and rodent testis: type-1 cannabinoid receptor and fatty acid amide hydrolase activity in male germ cells [19].
• Consistent with this distribution, in a de facto nociceptive sensory neuron population that exhibited vanilloid receptor type 1 immunoreactivity, colocalization with CB1 mRNA was also sparse (<5%) [23].
• We suggest that CB1-receptor upregulation in the ETB-mutant hippocampus reflects an attempt to compensate for the lack of ETB-receptors [32].

Analytical, diagnostic and therapeutic context of Cnr1

• To address this hypothesis, we evaluated the neuronal distribution of cannabinoid receptor type 1 (CB1) in the trigeminal ganglion (TG) of the adult rat through combined in situ hybridization (ISH) and immunohistochemistry (IHC) [23].
• In agreement with these results using RT-PCR, it was shown that neonatal cardiac cells express CB2, but not CB1 receptors [2].
• Cannabinoid receptor agonists produce analgesia for pains of non-cranial origin [3].
• Here we examined the expression of spinal cannabinoid-1-receptors (CB1Rs) following chronic constriction sciatic nerve injury (CCI) and its relation to the effects of a CBR agonist (Win 55,212-2) on neuropathic pain in rats [33].
• Therefore, we measured cannabinoid receptor 1 (CB1R) protein by Western blot and messenger RNA (mRNA) by reverse transcription-polymerase chain reaction in the pons of rats across the 24-h period [7].

References