Linked Life Data

17052840

Source:http://linkedlifedata.com/resource/pubmed/id/17052840

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-11-7
pubmed:abstractText
Compared to other M(1) muscarinic acetylcholine receptor (M(1) mAChR) agonists, xanomeline demonstrates both reversible and persistent modes of binding to the receptor. In our study, we investigated the long-term consequences of brief incubation of Chinese hamster ovary cells expressing M(1) mAChR (M(1)-CHO) with low concentrations of xanomeline followed by washing off the free drug. Thus, M(1)-CHO cells were exposed to 100 nM xanomeline for 1h then washed extensively. Washed cells were either used immediately for binding assays or incubated for 23 h in the absence of free xanomeline. Only the latter treatment conditions resulted in marked attenuation of binding of the muscarinic radioligand [(3)H]N-methylscopolamine ([(3)H]NMS) to intact cells. Shortening the xanomeline pretreatment period to 1 min had the same trends as the 1h pretreatment, implying that xanomeline binds instantly to the receptor to elicit long-term wash-resistant effects. Presence of atropine during the brief period of xanomeline pretreatment did not markedly modulate xanomeline's long-term effects, which suggests that persistent anchoring of the xanomeline molecule to the M(1) receptor takes place at a site distinct from the orthosteric binding domain. Our findings suggest the possibility of a time-dependent transition of the conformation of the muscarinic M(1) receptor-xanomeline complex between states that vary in their ability to bind [(3)H]NMS. However, possible involvement of other mechanisms of long-term receptor regulation cannot be discounted.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17052840-12021390, http://linkedlifedata.com/resource/pubmed/commentcorrection/17052840-12023535, http://linkedlifedata.com/resource/pubmed/commentcorrection/17052840-14565944, http://linkedlifedata.com/resource/pubmed/commentcorrection/17052840-14569060, http://linkedlifedata.com/resource/pubmed/commentcorrection/17052840-16364641, http://linkedlifedata.com/resource/pubmed/commentcorrection/17052840-16675658, http://linkedlifedata.com/resource/pubmed/commentcorrection/17052840-1710663, http://linkedlifedata.com/resource/pubmed/commentcorrection/17052840-2188581, http://linkedlifedata.com/resource/pubmed/commentcorrection/17052840-2265699, http://linkedlifedata.com/resource/pubmed/commentcorrection/17052840-9346340, http://linkedlifedata.com/resource/pubmed/commentcorrection/17052840-9614217
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0304-3940
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
410
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11-4
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Long-term wash-resistant effects of brief interaction of xanomeline at the M1 muscarinic receptor.
pubmed:affiliation
Division of Neuroscience Research in Psychiatry, University of Minnesota Medical School, Mayo Mail Code 392, 420 Delaware St. SE, Minneapolis, MN 55455, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural