Linked Life Data

10940778

Source:http://linkedlifedata.com/resource/pubmed/id/10940778

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-9-27
pubmed:abstractText
The structural basis for the selectivity of the antagonist UH-AH 37 at human muscarinic acetylcholine receptors was investigated by expressing mutant receptors in COS-7 cells. Previous studies have demonstrated that the interaction between UH-AH 37 and [(3)H]N-methylscopolamine in equilibrium assays is competitive and that the high affinity of UH-AH 37 for the M(5) subtype, compared to M(2), is due to an epitope in the sixth transmembrane domain (TM6) or the third outer loop of the receptor. By mutating each nonconserved residue in this region of M(2) and M(5) to its counterpart in the other receptor, we identified a threonine residue in the middle of TM6 uniquely responsible for the higher affinity of the M(5) receptor (M(1), M(3), and M(4) receptors also carry a threonine at that location and also have high affinity for UH-AH 37). The mutant receptor in which the corresponding alanine of the M(2) receptor was replaced by threonine, M(2)(401)ala --> thr, expressed enhanced affinity for pirenzepine as well as for UH-AH 37. The chick M(2) receptor, which expresses anomalously high affinity for pirenzepine, differs from its mammalian counterparts by the presence of a threonine at this position. Affinities of AF-DX 116 and 4-DAMP, as well as the allosteric potency of UH-AH 37, were not sensitive to the M(2)(401) ala --> thr mutation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0031-7012
pubmed:author
pubmed:copyrightInfo
Copyright 2000 S. Karger AG, Basel
pubmed:issnType
Print
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
62-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10940778-Amino Acid Sequence, pubmed-meshheading:10940778-Animals, pubmed-meshheading:10940778-Benzodiazepinones, pubmed-meshheading:10940778-Binding, Competitive, pubmed-meshheading:10940778-COS Cells, pubmed-meshheading:10940778-Dibenzazepines, pubmed-meshheading:10940778-Humans, pubmed-meshheading:10940778-Molecular Sequence Data, pubmed-meshheading:10940778-Muscarinic Antagonists, pubmed-meshheading:10940778-Mutagenesis, Site-Directed, pubmed-meshheading:10940778-Parasympatholytics, pubmed-meshheading:10940778-Pirenzepine, pubmed-meshheading:10940778-Receptor, Muscarinic M2, pubmed-meshheading:10940778-Receptor, Muscarinic M5, pubmed-meshheading:10940778-Receptors, Muscarinic, pubmed-meshheading:10940778-Sequence Homology, Amino Acid, pubmed-meshheading:10940778-Threonine, pubmed-meshheading:10940778-Transfection
pubmed:year
2000
pubmed:articleTitle
Site-directed mutagenesis implicates a threonine residue in TM6 in the subtype selectivities of UH-AH 37 and pirenzepine at muscarinic receptors.
pubmed:affiliation
Departments of Psychiatry and Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. jxe11@psu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.