Linked Life Data

7681831

Source:http://linkedlifedata.com/resource/pubmed/id/7681831

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1993-5-6
pubmed:abstractText
The NK1 (substance P) and NK3 (neurokinin B) receptors are G protein-coupled receptors sharing approximately 70% identity within the membrane-spanning domains. However, they each have a distinct pharmacological profile in respect of peptide binding. To identify epitopes that determine their selectivity for natural and synthetic tachykinin peptides, we constructed a series of chimeric NK1/NK3 receptors in which carboxyl-terminal segments of increasing length in the NK1 receptor were exchanged with the corresponding segments from the NK3 receptor. The general, structural integrity of the chimeric constructs was confirmed by the amphibian tachykinin peptide, eledoisin, which was recognized equally well by both of the wild-type receptors and bound with a similar or even higher affinity to all the chimeric receptors. Competition binding studies showed that the affinity of the two natural ligands, substance P and neurokinin B, changed gradually through the series of chimeric receptors indicating that several binding epitopes throughout the receptor structure are involved in the selective recognition of these peptides. However, whereas the single, largest change in binding affinity for substance P occurred when segments in the amino-terminal end of the receptor were exchanged, this occurred for neurokinin B in the carboxyl-terminal end of the receptor. The affinity of the NK1-selective ligand, [Sar9,Met(O2)11]SP, changed even more gradually through the series of chimeric receptors than that of substance P. In contrast, the NK3-selective hexapeptide, senktide, was recognized only when transmembrane segment III and IV from the NK3 receptor were incorporated into the chimeric constructs. These data suggest that several receptor domains contribute to the binding specificity of tachykinin agonists but in varying degrees for each peptide. It is concluded that the tachykinin peptides, in partially different ways, interact with multiple epitopes scattered throughout the receptor structure, but conceivably these epitopes are closely located in space around a hypothetical receptor center.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
268
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7893-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Chimeric NK1 (substance P)/NK3 (neurokinin B) receptors. Identification of domains determining the binding specificity of tachykinin agonists.
pubmed:affiliation
University Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't