Linked Life Data

7681152

Source:http://linkedlifedata.com/resource/pubmed/id/7681152

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6418
pubmed:dateCreated
1993-4-16
pubmed:abstractText
Non-peptide ligands for peptide receptors have been discovered in several systems through file screening programs, but the mechanism of action for these candidate drugs is obscure as they do not chemically resemble the native peptides. The compound CP 96345 is a high-affinity, non-peptide antagonist of the substance P (NK1) receptor, which is important in pain perception and neurogenic inflammation. Here we identify epitopes on the NK1 receptor responsible for the specific binding of CP 96345 by systematic exchange of corresponding segments between the NK1 receptor and the homologous NK3 (neurokinin B) receptor, which does not bind the non-peptide ligand. Non-conserved residues, in two epitopes around the top of transmembrane segment V and in one epitope at the top of transmembrane segment VI, are essential for the specific action of CP 96345 on the NK1 receptor, but are surprisingly not important for the binding of the natural peptide ligand, substance P. Susceptibility to the non-peptide antagonists can be conveyed to the previously unresponsive NK3 receptor by mutational transfer of this discontinuous epitope from the NK1 receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0028-0836
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
362
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
345-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Different binding epitopes on the NK1 receptor for substance P and non-peptide antagonist.
pubmed:affiliation
University Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't