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1 VR1 agonist capsaicin (CAP; 100 nm) reversibly increased
2 VR1 immunoreactivity in terminals in lamina I is in good
3 VR1 is also activated by protons, indicating that it may
4 VR1 is gated by protons, heat, and the pungent ingredien
5 VR1 nerves were also observed within the muscle layers a
6 VR1 responds to noxious stimuli including capsaicin, the
7 VR1 was C-terminally tagged with either the 27-kDa enhan
8 VR1, which binds and is activated by capsaicin and other
9 VR1-/- mice showed normal responses to noxious mechanica
10 VR1-immunopositive cells also were found in the third an
11 VR1-like fibers appear to be predominantly spinal in ori
12 VR1-like immunoreactivity was observed on nerves within
13 VR1-like nerves and other immunopositive cells were also
14 monary C-fibres to the vanilloid receptor 1 (VR1) agonist capsaicin was dependent on conduction veloc
15 of the heat-sensitive vanilloid receptor 1 (VR1) and sensitivity to capsaicin were used to character
16 was not affected by a vanilloid receptor 1 (VR1) antagonist, capsazepine (10 microM), and was rapidl
20 afferents that express vanilloid receptor 1 (VR1), a receptor for noxious heat, are essential for the
22 -rich" neurons; or the vanilloid receptor 1 (VR1), identifying neurons activated by heat, acid, and c
23 eral afferents express vanilloid receptor 1 (VR1), little is known about their functional properties
24 abelling revealed that vanilloid receptor 1 (VR1)-containing afferent nerve fibres were present on th
30 he capsaicin receptor, vanilloid receptor-1 (VR1), is an important cation channel present on primary
33 ecently cloned vanilloid receptor subtype 1 (VR1) is a ligand-gated channel that is activated by caps
34 etabosensitive vanilloid receptor subtype 1 (VR1), inducing a neurally mediated pressor response, and
35 o known as the vanilloid receptor subtype 1 (VR1), is a heat-gated ion channel that has been proposed
37 a cDNA clone, vanilloid receptor subtype-1 (VR1), was isolated and found to encode an ion channel th
39 he transient receptor potential vanilloid 1 (VR1) in mediating the altered sensitivity of muscle affe
40 tivation (Hill coefficient congruent with 1, VR1 congruent with 2), is much more selective for Ca(2+)
45 ptic enhancement of GABA release caused by a VR1-mediated increase in glutamate release from presynap
47 imide, a PKC inhibitor, and ruthenium red, a VR1 ionophore blocker, but not capsazepine, a vanilloid
49 However, because dorsal rhizotomy abolishes VR1 staining in both laminae I and II, it is suggested t
51 th previous reports, we found that VRL-1 and VR1 are expressed in different dorsal root ganglion (DRG
54 tive endocannabinoid receptors CB1, CB2, and VR1 were expressed in HSCs, specific receptor blockade f
59 anilloid receptor TRPV1, previously known as VR1, has been implicated in pain sensation under both ph
61 lusively associated with unmyelinated axons, VR1 identifies C-fiber afferent pathways within the brai
63 ator phorbol 12-myristate 13-acetate blunted VR1 desensitization, and this effect was reversible in t
65 nd that most NK1-positive cells contacted by VR1-positive fibers project to the lateral parabrachial
67 nal evidence that the heart is innervated by VR1-expressing afferent nerves and these afferent nerves
71 which can either enhance (e.g. 5-HT3, CCK1, VR1 and NK1 receptors) or reduce (e.g. ghrelin, leptin,
72 losely related, nonselective cation channels VR1, VRL-1, OTRPC4 (also known as VR-OAC, Trp12, and VRL
73 dentification of the heat-sensitive channels VR1 and VRL-1, demonstrate that TRP channels detect temp
75 sitive lamina I neurons by fibers containing VR1, these results demonstrate a significant monosynapti
77 ystem, neonatal capsaicin treatment depleted VR1 mRNA from the spinal nucleus of the trigeminal nerve
79 VR1 expression systems as well as endogenous VR1 expressed in dorsal root ganglion cells, we analyzed
80 effort to optimize conditions for evaluating VR1 pharmacology, we found that treatment of Chinese ham
81 primary sensory neurons endogenously express VR1, and resiniferatoxin treatment induced a sudden incr
88 investigated in cells ectopically expressing VR1 and primary cultures of dorsal root ganglion neurons
89 both the DRG neurones and oocytes expressing VR1, the chord conductances at -60 and +60 mV were appro
94 fore combined immunofluorescent staining for VR1 and NK1 to show that NK1-positive neurons in lamina
95 erve attached native synapses and tested for VR1 and P2X function primarily in spindle-shaped neurons
97 -splice variant (VR.5'sv) which differs from VR1 by elimination of the majority of the intracellular
99 r dorsal root ganglion neurons isolated from VR1-null mice lacked many of the capsaicin-, acid- and h
101 hat 91% of the P1.19,15 strains analyzed had VR1 and VR2 sequences identical to those of the prototyp
105 saicin inhibited [(3)H]RTX binding to HEK293/VR1 cells with K(i) values of 0.4 and 4.0 microM, respec
107 site flanking exon-intron 7 in rat and human VR1 diverged from the expected consensus sequence; this
108 d PKA in inflammatory pain hypersensitivity, VR1 phosphorylation at Ser116 by PKA may represent an im
112 d STEARDA failed to affect calcium influx in VR1-transfected human embryonic kidney (HEK) 293 cells o
115 ular evidence for stimulus-specific steps in VR1 activation and offer strategies for the development
116 ates PKC, acutely activated Ca(2+) uptake in VR1-expressing cells at pH 5.5, but not at mildly acidic
119 activation of protein kinase C (PKC) induces VR1 channel activity at room temperature in the absence
120 trate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of
121 Although VRL-1 does not bind capsaicin, like VR1 it is activated by noxious heat (>52 degrees C).
125 ith different ratios of wild-type and mutant VR1 is consistent with tetrameric stoichiometry for the
133 ty of PKC is required for PDBu activation of VR1 ion conductance, and is independent of the vanilloid
136 the heat-induced single-channel activity of VR1, in an attempt to localize the temperature-dependent
139 of iodo-RTX, a highly specific antagonist of VR1 receptors, blocked capsaicin- but not bradykinin-ind
144 nd immunostaining to estimate the density of VR1 in colonic tissues of patients with inflammatory bow
146 the expression and intracellular dynamics of VR1 in lamina II neurons are controlled by presynaptic i
148 investigated the function and expression of VR1 in dorsal root ganglion (DRG) neurons isolated from
150 l sensitivity in vivo requires expression of VR1, a heat-activated ion channel on sensory neurons.
152 ing C-terminally tagged recombinant forms of VR1 with an EC(50) = approximately 10 microm at pH 5.5.
153 inactivating mechanism acts independently of VR1, has characteristics similar to acid sensing ion cha
157 iting hypothesis because the localization of VR1 overlaps with that of anandamide and its preferred c
159 ve isoform by targeting several mutations of VR1 at highly conserved amino acids or at residues of po
161 ent with a model in which phosphorylation of VR1 by PKC increases the probability of channel gating b
163 overlapping ligand recognition properties of VR1 and CB(1) might be exploited by medicinal chemistry.
164 was confirmed by a substantial reduction of VR1 immunoreactivity in the epicardium and dorsal root g
172 hopeptide mapping, and protein sequencing of VR1 cytoplasmic domains delineate several candidate PKA
177 uggest that either native VRs are made up of VR1 subunits, or the incorporation of subunits other tha
178 the present study, we determined the role of VR1s in activation of cardiac spinal afferent nerves cau
180 hat activation of PKC does not directly open VR1 channels, but instead increases the probability that
181 ergic terminals into either P2X sensitive or VR1 sensitive that correspondingly identify myelinated a
183 icin receptor vanilloid receptor 1 (TRPV1 or VR1) was changed in rectal sensory fibres, and to correl
190 ry (CHO) cells heterologously expressing rat VR1 (CHO/rVR1) with butyrate enhanced rVR1 expression an
191 ), that function as partial agonists for rat VR1 heterologously expressed in Chinese hamster ovary ce
192 ed activity compared with capsazepine on rat VR1 expressed in Chinese hamster ovary (CHO) cells.
193 have now characterized ligand binding to rat VR1 expressed in human embryonic kidney (HEK293) and Chi
194 Reverse transcription-PCR performed with rat VR1-specific primers verified the expression of VR1 mRNA
197 nal cord that express the vanilloid receptor VR1 are from small and medium dorsal root ganglion (DRG)
203 ive neurons expressed the vanilloid receptor VR1, a heat-sensitive receptor expressed by many IB4-pos
204 immunoreactivity for the vanilloid receptor VR1, another protein associated primarily with C-type ne
205 Its molecular target, the vanilloid receptor VR1, was recently cloned and confirmed functionally as a
213 The recently cloned vanilloid receptor (VR1) is postulated to account for heat and capsaicin sen
217 TRPV1; also known as the vanilloid receptor, VR1) in nociceptive neurons of the dorsal root and trige
221 this study, we demonstrate that PKA reduces VR1 desensitization and directly phosphorylates VR1.
222 -acid extracellular domain variable regions (VR1 and VR2), whereas intratypic variability localizes p
223 ecificity, we identified 3 variable regions (VR1, -2, and -3) in the ADAMTS family metalloprotease do
224 ischemia, or traumatic injury can sensitize VR1 to eicosanoids and transduce pain from the periphery
226 hannel opening in response to these stimuli, VR1 and six channels containing charge neutralization po
229 Co-immunoprecipitation of differently tagged VR1 molecules indicated that VR1 can form oligomers.
233 Colocalization studies demonstrated that VR1 expression was increased in large myelinated A-fiber
239 pathways in VR activation; it is known that VR1 is also expressed in non-sensory tissue and may medi
240 ciception and hyperalgesia, we reasoned that VR1-positive fibers may terminate onto NK1-expressing do
249 the discovery of new drugs that can bind the VR1 receptor, or antagonise endogenous inflammatory subs
253 which are both likely to be derived from the VR1 gene product, account for the membrane responses to
254 de substitutions at defined locations in the VR1 (variable region 1) segment of the mtd (major tropis
255 cts were blocked by co-administration of the VR1 antagonist iodo-resiniferatoxin (10 nm for HEK cells
256 nsmembrane domain disrupts activation of the VR1 receptor by both capsaicin and resiniferatoxin.
257 l horn from birth and that activation of the VR1 receptor increases spontaneous glutamate release via
258 with altered cell-specific expression of the VR1 receptor that is coupled to increased function throu
259 f CHF rats whereas the immunostaining of the VR1 receptors was decreased in IB4-positive neurons.
260 lar free calcium and confocal imaging of the VR1-green fluorescent fusion protein revealed that, at l
261 lpha) in dorsal root ganglion neurons or the VR1 cell lines, whereas only partially influencing PKCbe
262 such non-CB1, SR141716A-sensitive site, the VR1 vanilloid receptor, was tested by administering SR14
272 results emphasize that VRL-1, in contrast to VR1, is present in a diverse population of neurons and u
274 Since VR.5'sv is otherwise identical to VR1 throughout its transmembrane spanning domains and C-
275 es to painful stimuli in animals have led to VR1 being considered as important for pain sensation.
276 we hypothesized that the pressor response to VR1 stimulation would be smaller and the sensitizing eff
277 control animals, cardiovascular responses to VR1 stimulation are blunted and P2X-mediated responses a
278 or, was tested by administering SR141716A to VR1-KO mice, in which the ability of SR141716A to enhanc
279 levels, of the heat-gated ion channel TRPV1 (VR1) in these cells, which is then transported to periph
280 Animals expressing the mammalian TRPV1 (VR1) channel in ASH nociceptor neurons avoid the TRPV1 l
282 ive mutation when coexpressed with wild-type VR1, providing functional evidence that the VR1 receptor
283 ore sensitive to capsaicin than is wild-type VR1, whereas none differed in their activation by acidic
289 ol/L, 20 minutes), or blockade of vanilloid (VR1) receptors using capsazepine (3 micromol/L) inhibite
292 itization of VR1 was down-regulated, whereas VR1 re-sensitization was up-regulated in DRG neurons fro
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