Linked Life Data

18305010

Source:http://linkedlifedata.com/resource/pubmed/id/18305010

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-5-16
pubmed:abstractText
We measured the influence of gallamine on the functional responses and binding properties of selected agonists at the M(2) muscarinic receptor and analyzed the data within the context of the allosteric ternary complex model. Our analysis showed that gallamine modified agonist affinity without influencing efficacy. To explain this behavior, we investigated the allosteric ternary complex model at a deeper level of analysis to assess allosterism in terms of the differential affinity of gallamine for ground and active states of the receptor. Our simulations showed that two-state models based on a single orthosteric site for the agonist linked to an allosteric site for gallamine could not account for affinity-only modulation, even if multiple conformations of ground and active states were considered. We also expanded the tandem two-site model (J Biol Chem 275:18836-18844, 2000) within the context of the allosteric ternary complex model and analyzed the resulting hybrid model at the level of receptor states. This model posits that the agonist first binds to a relay site and then shuttles to the activation site to turn on the receptor. If it is assumed that allosterism occurs at the relay site and not the activation site, then this model can account for affinity-only modulation in a manner consistent with the allosteric ternary complex model.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
325
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1039-60
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Two-state models and the analysis of the allosteric effect of gallamine at the M2 muscarinic receptor.
pubmed:affiliation
Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697-4625, USA. fjehlert@uci.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural