Disease relevance of Trpv1

• Both VR.5'sv and VR1 mRNA were shown to be expressed in tissues reportedly responsive to capsaicin including dorsal root ganglion, brain, and peripheral blood mononuclear cells [1].
• First, using capsaicin-induced hyperalgesia as a measure of VR1 function, we found that vanilloid receptors were functional as early as postnatal day 10 (P10), although hyperalgesia was of longer duration in adult [2].
• Endocannabinoids induce ileitis in rats via the capsaicin receptor (VR1) [3].
• Early painful diabetic neuropathy is associated with differential changes in the expression and function of vanilloid receptor 1 [4].
• AT-induced effects including reduction of hypotension (n = 5) and inhibition of induction of iNOS (n = 4 or 5) and TNF- alpha (n = 5) in the lungs of endotoxin-treated animals were completely reversed by pretreatment with capsazepine (CPZ) (n = 4 or 5), a vanilloid receptor antagonist, or CGRP(8-37), a CGRP receptor antagonist (n = 4 or 5) [5].

Psychiatry related information on Trpv1

• BACKGROUND: Effects of vanilloid-receptor agonists and antagonists on HCl-induced gastric lesions in rats were investigated to elucidate the role of vanilloid receptor type 1 (VR1) in gastric mucosal defense mechanisms [6].

High impact information on Trpv1

• Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition [7].
• The selective 'vanilloid receptor' antagonist capsazepine inhibited anandamide-induced vasodilation and release of CGRP [8].
• In patch-clamp experiments on cells expressing the cloned vanilloid receptor (VR1), anandamide induced a capsazepine-sensitive current in whole cells and isolated membrane patches [8].
• The vanilloid receptor may thus be another molecular target for endogenous anandamide, besides cannabinoid receptors, in the nervous and cardiovascular systems [8].
• The cloned capsaicin receptor, also known as the vanilloid receptor subtype 1 (VR1), is a heat-gated ion channel that has been proposed to mediate responses of small-diameter sensory neurons to moderate (43 degrees C) thermal stimuli [9].

Chemical compound and disease context of Trpv1

• Consistent with these observations, the number of dorsal root ganglion neurons coexpressing VR1 and isolectin B4 binding sites doubled while the number of neurons that had both VR1 and substance P remained relatively constant from P2 to P10 [2].
• Here we investigated the function and expression of VR1 in dorsal root ganglion (DRG) neurons isolated from streptozotocin-induced diabetic rats between 4 and 8 weeks after onset of diabetes [4].
• Anandamide excites central terminals of dorsal root ganglion neurons via vanilloid receptor-1 activation [10].
• Capsaicin antagonists including ruthenium red, capsazepine and iodo-resiniferatoxin (I-RTX) have recently been shown to inhibit the activation by noxious heat of the capsaicin receptor (TRPV1) expressed in non-neuronal host cells, and natively, in cultured dorsal root ganglion cells [11].
• Bradykinin interacts with the bradykinin B2 receptor on dorsal root ganglion (DRG) neurons, setting off a series of reactions inside the cells that ultimately make the vanilloid receptor 1 more sensitive to a normal stimulus by activating various enzymes coupled with second messenger signaling cascades [12].

Biological context of Trpv1

• Here, we report the isolation of a vanilloid receptor 5'-splice variant (VR.5'sv) which differs from VR1 by elimination of the majority of the intracellular N-terminal domain and ankyrin repeat elements [1].
• Morphological evidence for functional capsaicin receptor expression and calcitonin gene-related peptide exocytosis in isolated peripheral nerve axons of the mouse [13].
• These data indicate that in addition to activation of cannabinoid type 1, anandamide may serve as an endogenous compound to stimulate VR1, leading to a decrease in blood pressure via CGRP release from sensory nerve terminals [14].
• A lesion of the inferior alveolar nerve, which supplies mandibular teeth and gingiva, resulted in a marked down-regulation of VR1 in the affected trigeminal ganglion cells [15].
• These data suggest that VR1-positive sensory nerves in the kidney enhance renal excretory function, a mechanism that may be critically involved in sodium and fluid homeostasis [16].

Anatomical context of Trpv1

• The vanilloid receptor subtype 1 (VR1) is expressed almost exclusively in the primary sensory nerves and cell bodies of these sensory neurons [17].
• Rutaecarpine (Rut) can relax vascular smooth muscle via stimulation of calcitonin gene-related peptide (CGRP) release by activation of VR1 [17].
• From embryonic day 16 to P20, the majority of VR1 protein in the spinal cord was observed in lamina I [2].
• Expression of calcitonin gene-related peptide (CGRP) and the vanilloid receptor TRPV1 was quantified in these backlabelled cells and was enriched in the knee afferents in all animals studied, compared to the expression in neurons across the whole dorsal root ganglia (DRG) [18].
• Many VR1-positive nerve fibers surrounded the furrows of the circumvallate and foliate papillae, forming plexuses [19].

Associations of Trpv1 with chemical compounds

• Recently a cDNA clone, vanilloid receptor subtype-1 (VR1), was isolated and found to encode an ion channel that is activated by both capsaicin, the pain producing compound in chili peppers, and by noxious thermal stimuli [1].
• CONCLUSION: These results suggest, for the first time, that the hypotensive effect of Rut is mediated by stimulation of CGRP synthesis and release via activation of VR1 in the phenol-induced hypertensive rat [17].
• The effects of anandamide and 2-AG were significantly inhibited by pretreatment with the specific capsaicin receptor (vanilloid receptor subtype 1; VR1) antagonist capsazepine [3].
• Capsaicin perfusion into the left renal pelvis but not intravenously caused significant increases in urine flow rate and urinary sodium excretion bilaterally in a dose-dependent manner, which were abolished by capsazepine, a selective VR1 receptor antagonist, given ipsilaterally to the renal pelvis or by ipsilateral renal denervation [16].
• Most of VR1 immunoreactive nerves were also immunoreactive for SP or CGRP [20].

Regulatory relationships of Trpv1

• Vanilloid receptor-like protein-1-expressing neurons did not express the vanilloid receptor 1 [21].
• The activation of transient receptor potential vanilloid receptor 1 (TRPV1) by capsaicin in rat brain stimulates gastric acid secretion via tachykinin NK2 receptors and the vagus cholinergic nerve, but the involvement of other receptor systems has not been elucidated [22].
• The thermal hyperalgesia following an intraplantar (i.pl.) administration of the PAR-2-activating peptide SLIGRL-NH2 was completely abolished by the capsaicin receptor antagonist capsazepine [23].
• Furthermore, A-fibers in the uninjured L4 DRG after L5 spinal nerve ligation that have increased mGluR5 are the same A-fibers that newly express vanilloid receptor 1 after such injury [24].

Other interactions of Trpv1

• The co-expression of VR1 and VRL-1 in the rat vagal sensory ganglia [25].
• The vanilloid receptor-1 (TRPV1), the capsaicin receptor, a transducer of several nociceptive stimuli, is principally expressed by nociceptive fibers that specifically target supraspinal-projecting neurons expressing the NK1 receptor [26].
• Western blot showed that protein expression for the calcitonin receptor-like receptor-but not receptor activity modifying protein 1, VR1, and cannabinoid type 1 receptors-was increased in mesenteric resistance arteries in SHR compared with WKY (P<0.05) [14].
• Existence of brain-derived neurotrophic factor and vanilloid receptor subtype 1 immunoreactive sensory DRG neurons innervating L5/6 intervertebral discs in rats [27].
• The membrane-bound CA isoforms IV, IX, XII, and XIV and cytosolic CA II and the vanilloid receptor 1 (TRPV1) were expressed in duodenum and stomach [28].

Analytical, diagnostic and therapeutic context of Trpv1

• Molecular cloning of an N-terminal splice variant of the capsaicin receptor. Loss of N-terminal domain suggests functional divergence among capsaicin receptor subtypes [1].
• The distribution of VR1 receptors in peripheral and central processes of rat primary vagal afferent neurons innervating the gastrointestinal tract was investigated by immunohistochemistry [29].
• By immunofluorescence and flow cytometry, we found that a substantial portion of CD5+ thymocytes, namely CD4+ and double negative (DN) cell subsets, express VR1 that was present on plasma membrane on discrete spots [30].
• VR1 mRNA was identified by quantitative RT-PCR in CD5(+) thymocytes [30].
• VR1, but not P2X(3), increases in the spared L4 DRG in rats with L5 spinal nerve ligation [31].

References