Linked Life Data

11698581

Source:http://linkedlifedata.com/resource/pubmed/id/11698581

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2001-11-7
pubmed:abstractText
The recently cloned vanilloid receptor subtype 1 (VR1) is a ligand-gated channel that is activated by capsaicin, protons, and heat. We have attempted to develop a dominant negative isoform by targeting several mutations of VR1 at highly conserved amino acids or at residues of potential functional importance and expressing the mutants in Chinese hamster ovary cells. Mutation of three highly conserved amino acid residues in the putative sixth transmembrane domain disrupts activation of the VR1 receptor by both capsaicin and resiniferatoxin. The vanilloid binding site in this mutant is intact, although the affinity for [(3)H]resiniferatoxin (RTX) is diminished by nearly 40-fold. Interestingly, this mutant retains a significant but diminished response to protons, supporting the existence of multiple gating mechanisms for different stimuli. The mutant appears to function by interfering with the gating induced by vanilloids rather than the expression level or permeability of the receptor. In addition, this mutant was found to function as a strong dominant negative mutation when coexpressed with wild-type VR1, providing functional evidence that the VR1 receptor forms a multimeric complex. Analysis of both current density and [(3)H]RTX affinity in cells cotransfected with different ratios of wild-type and mutant VR1 is consistent with tetrameric stoichiometry for the native capsaicin receptor.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8697-706
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11698581-Amino Acid Substitution, pubmed-meshheading:11698581-Animals, pubmed-meshheading:11698581-Binding Sites, pubmed-meshheading:11698581-CHO Cells, pubmed-meshheading:11698581-Capsaicin, pubmed-meshheading:11698581-Conserved Sequence, pubmed-meshheading:11698581-Cricetinae, pubmed-meshheading:11698581-Diterpenes, pubmed-meshheading:11698581-Gene Expression, pubmed-meshheading:11698581-Genes, Dominant, pubmed-meshheading:11698581-Ion Channel Gating, pubmed-meshheading:11698581-Macromolecular Substances, pubmed-meshheading:11698581-Mutagenesis, Site-Directed, pubmed-meshheading:11698581-Patch-Clamp Techniques, pubmed-meshheading:11698581-Protein Binding, pubmed-meshheading:11698581-Protein Structure, Tertiary, pubmed-meshheading:11698581-Rats, pubmed-meshheading:11698581-Receptor Aggregation, pubmed-meshheading:11698581-Receptors, Drug, pubmed-meshheading:11698581-Sequence Homology, Amino Acid, pubmed-meshheading:11698581-Structure-Activity Relationship, pubmed-meshheading:11698581-TRPV Cation Channels, pubmed-meshheading:11698581-Transfection
pubmed:year
2001
pubmed:articleTitle
Functional analysis of capsaicin receptor (vanilloid receptor subtype 1) multimerization and agonist responsiveness using a dominant negative mutation.
pubmed:affiliation
Department of Cell and Molecular Physiology and the Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't