Disease relevance of Trpv1

• BACKGROUND AND AIMS: Activation of the vanilloid receptor subtype 1 (VR-1) results in release of proinflammatory peptides which initiate an inflammatory cascade known as neurogenic inflammation [1].
• These results demonstrate that repeated caerulein stimulation causes experimental pancreatitis that is mediated in part by stimulation of VR1 on primary sensory neurons, resulting in endogenous SP release [2].
• The purpose of this study was to examine the involvement of the transient receptor potential vanilloid receptor 1 (TRPV1) in inflammatory processes observed in murine allergic contact dermatitis (ACD) [3].
• Dendritic cells expressed mRNA for cannabinoid receptor 1 (CB(1)), cannabinoid CB(2) receptor, and vanilloid receptor 1 (TRPV1) and the addition of the G(i) inhibitor, pertussis toxin, completely attenuated suppression induced by 3 and 6 muM THC but not by 10 muM THC [4].
• Possible involvement of P2Y2 metabotropic receptors in ATP-induced transient receptor potential vanilloid receptor 1-mediated thermal hypersensitivity [5].

High impact information on Trpv1

• It is found in a subset of nociceptive sensory neurons where it is coexpressed with TRPV1/VR1 (the capsaicin/heat receptor) but not TRPM8 [6].
• VR1 responds to noxious stimuli including capsaicin, the pungent component of chilli peppers, heat and extracellular acidification, and it is able to integrate simultaneous exposure to these stimuli [7].
• Small diameter dorsal root ganglion neurons isolated from VR1-null mice lacked many of the capsaicin-, acid- and heat-gated responses that have been previously well characterized in small diameter dorsal root ganglion neurons from various species [7].
• Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia [7].
• The vanilloid receptor-1 (VR1) is a ligand-gated, non-selective cation channel expressed predominantly by sensory neurons [7].

Chemical compound and disease context of Trpv1

• Capsaicin vanilloid receptor-1 mediates substance P release in experimental pancreatitis [2].
• By contrast, the CB1 cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716; SR1), capsazepine (vanilloid receptor antagonist), the inhibitors of ceramide generation, or pertussis toxin did not counteract CBD effects [8].
• Vasorelaxation by abn-cbd is endothelium-dependent, pertussis toxin-sensitive, and is inhibited by the BK(Ca) channel inhibitor charybdotoxin, but not by the nitric-oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester or by the vanilloid VR1 receptor antagonist capsazepine [9].
• Prostaglandin and protein kinase A-dependent modulation of vanilloid receptor function by metabotropic glutamate receptor 5: potential mechanism for thermal hyperalgesia [10].

Biological context of Trpv1

• Sex differences in CGRP(+/+) mice were eliminated by pretreatment with SB366791 (500 mug/kg intraperitoneally), a vanilloid receptor antagonist, and by ovariectomy [11].
• Engagement of VR1 on immature DCs such as by treatment with CP leads to maturation of DCs as measured by up-regulation of antigen-presenting and costimulatory molecules [12].
• Anandamide, a VR1 agonist in acidic conditions, acts additively with PDBu and remains effective after chronic PKC down-regulation [13].
• However, AEA also binds to vanilloid (VR1) receptors and induces cell death in several cell lines [14].
• Daily body temperature (DBT) rhythm of mice lacking one of the transient receptor potential (TRP) family of proteins, the capsaicin receptor or TRPV1, was recorded by biotelemetry and found to have significantly higher amplitude than that of wild-type mice [15].

Anatomical context of Trpv1

• Double-labelling experiments with cytochemical markers of dorsal root ganglia neurons showed that approximately 95% of EM2-immunoreactive cell bodies also label with SP antisera, 83% co-express vanilloid receptor subtype 1/capsaicin receptor, and 17% label with isolectin B4, a marker of non-peptide nociceptors [16].
• These VR1-positive neurons were partly binding to lectin I-B4, indicating VR1-expression in non-peptidergic upper airway C-fibers [17].
• The release of these neuropeptides from primary afferent (sensory) nerve endings to various stimuli is considered to be induced by activation of the capsaicin (vanilloid) receptor (VR1) [17].
• Expression of substance P and vanilloid receptor (VR1) in trigeminal sensory neurons projecting to the mouse nasal mucosa [17].
• We demonstrate here that the dendritic cell (DC), a key cell type of the vertebrate immune system, expresses VR1 [12].

Associations of Trpv1 with chemical compounds

• Unlike their wild-type counterparts, SON neurons in Trpv1 knockout (Trpv1(-/-)) mice could not generate ruthenium red-sensitive increases in membrane conductance and depolarizing potentials in response to hyperosmotic stimulation [18].
• Moreover, Trpv1(-/-) mice showed a pronounced serum hyperosmolality under basal conditions and severely compromised AVP responses to osmotic stimulation in vivo [18].
• A subset of animals were administered the VR-1 antagonist capsazepine, famotidine, or omeprazole one hour before surgery [1].
• Here, we show that bradykinin- or NGF-mediated potentiation of thermal sensitivity in vivo requires expression of VR1, a heat-activated ion channel on sensory neurons [19].
• SR141716A, per se, but not the vanilloid VR1 receptor antagonist capsazepine, enhanced fluid accumulation induced by CT, whereas the selective inhibitor of anandamide cellular uptake, VDM11, prevented CT-induced fluid accumulation [20].

Regulatory relationships of Trpv1

• In addition, all beta-subunit of oncostatin M receptor-positive neurons expressed both vanilloid receptor 1 and P2X3 purinergic receptor [21].
• Interestingly, cannabinoid and vanilloid receptors display an overlap in ligand recognition properties, and the frequently used CB1 receptor antagonist SR141716A also inhibits vanilloid receptor-mediated responses [22].
• In the present study, we show that peripheral administration of TNFalpha induces thermal hypersensitivity in wild-type mice but not in transient receptor potential vanilloid receptor TRPV1(-/-) mice [23].

Other interactions of Trpv1

• In addition, OSMR-positive neurons decreased, resulting in the reduced number of VR1/P2X3/OSMR-triple positive neurons [24].
• Furthermore, the CB(1) and VR1 receptor antagonists did not block the effects of AEA on Fos immunoreactivity [25].
• Antagonism of either the vanilloid receptor transient receptor vanilloid 1 or the substance P receptor NK1-R had no effect on elastase-mediated lung injury in NEP-deficient mice [26].
• A high expression level of the VR-1 like protein (VRL-1) was observed in peritoneal macrophages, while the expression of VR-1 was not detected [27].
• Methylation of the amide group decreased the activity at VR1, AMT, and FAAH [28].

Analytical, diagnostic and therapeutic context of Trpv1

• METHODS: Oesophagitis was induced by pyloric ligation in wild-type and VR-1 deficient mice [1].
• Here we have disrupted the mouse VR1 gene using standard gene targeting techniques [7].
• By in situ hybridization and immunostaining, we confirmed that TGR7 mRNA was co-expressed in the small diameter neurons with P2X3 and VR1, both in rat and monkey dorsal root ganglia [29].
• 2. Whole cell voltage clamp techniques were used to examine the efficacy of AEA and related analogues methanandamide and N-(4-hydroxyphenyl)-arachidonylamide (AM404) at native VR1 receptors in acutely isolated mouse trigeminal neurons [30].
• [3H]Resiniferatoxin autoradiography in the CNS of wild-type and TRPV1 null mice defines TRPV1 (VR-1) protein distribution [31].

References