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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-9-20
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pubmed:abstractText |
1-((R)-5-tert-butyl-indan-1-yl)-3-isoquinolin-5-yl-urea (A-778317) is a novel, stereoselective, competitive antagonist that potently blocks transient receptor potential vanilloid-1 (TRPV1) receptor-mediated changes in intracellular calcium concentrations (pIC50 = 8.31 +/- 0.13). The (S)-stereoisomer, 1-((S)-5-tert-butyl-indan-1-yl)-3-isoquinolin-5-yl-urea (A-778316), is 6.8-fold less potent (pIC50 = 7.47 +/- 0.07). A-778317 also potently blocks capsaicin and acid activation of native rat TRPV1 receptors in dorsal root ganglion neurons. A-778317 was tritiated ([3H]A-778317; 29.3 Ci/mmol) and used to study recombinant human TRPV1 (hTRPV1) receptors expressed in Chinese ovary cells (CHO) cells. [3H]A-778317 labeled a single class of binding sites in hTRPV1-expressing CHO cell membranes with high affinity (KD = 3.4 nM; Bmax = 4.0 pmol/mg protein). Specific binding of 2 nM [3H]A-778317 to hTRPV1-expressing CHO cell membranes was reversible. The rank-order potency of TRPV1 receptor antagonists to inhibit binding of 2 nM [3H]A-778317 correlated well with their functional potencies in blocking TRPV1 receptor activation. The present data demonstrate that A-778317 blocks polymodal activation of the TRPV1 receptor by binding to a single high-affinity binding site and that [3H]A-778317 possesses favorable binding properties to facilitate further studies of hTRPV1 receptor pharmacology.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-3565
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pubmed:author |
pubmed-author:BianchiBruce RBR,
pubmed-author:El KouhenRachidR,
pubmed-author:FaltynekConnie RCR,
pubmed-author:GomtsyanArthurA,
pubmed-author:JarvisMichael FMF,
pubmed-author:LeeChih-HungCH,
pubmed-author:McDonaldHeath AHA,
pubmed-author:MorelandRobert BRB,
pubmed-author:NeelandsTorben RTR,
pubmed-author:PuttfarckenPamela SPS,
pubmed-author:RajaShirish NSN,
pubmed-author:SurberBruceB,
pubmed-author:SurowyCarol SCS,
pubmed-author:VaidyanathanSriajan NSN
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pubmed:issnType |
Print
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pubmed:volume |
323
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
285-93
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pubmed:meshHeading |
pubmed-meshheading:17660385-Animals,
pubmed-meshheading:17660385-Binding, Competitive,
pubmed-meshheading:17660385-CHO Cells,
pubmed-meshheading:17660385-Calcium Signaling,
pubmed-meshheading:17660385-Cell Membrane,
pubmed-meshheading:17660385-Cricetinae,
pubmed-meshheading:17660385-Cricetulus,
pubmed-meshheading:17660385-Ganglia, Spinal,
pubmed-meshheading:17660385-Humans,
pubmed-meshheading:17660385-Isoquinolines,
pubmed-meshheading:17660385-Ligands,
pubmed-meshheading:17660385-Molecular Structure,
pubmed-meshheading:17660385-Neurons, Afferent,
pubmed-meshheading:17660385-Radioligand Assay,
pubmed-meshheading:17660385-Rats,
pubmed-meshheading:17660385-Recombinant Proteins,
pubmed-meshheading:17660385-Stereoisomerism,
pubmed-meshheading:17660385-TRPV Cation Channels,
pubmed-meshheading:17660385-Transfection,
pubmed-meshheading:17660385-Tritium,
pubmed-meshheading:17660385-Urea
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pubmed:year |
2007
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pubmed:articleTitle |
[3H]A-778317 [1-((R)-5-tert-butyl-indan-1-yl)-3-isoquinolin-5-yl-urea]: a novel, stereoselective, high-affinity antagonist is a useful radioligand for the human transient receptor potential vanilloid-1 (TRPV1) receptor.
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pubmed:affiliation |
Department of Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R4PM, AP9A/2, 100 Abbott Park Rd, Abbott Park, IL 60064-6123, USA.
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pubmed:publicationType |
Journal Article
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