Linked Life Data

11723245

Source:http://linkedlifedata.com/resource/pubmed/id/11723245

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-11-27
pubmed:abstractText
The recently cloned canine P2Y11 receptor (cP2Y11) and its human homolog (hP2Y11) were stably expressed in Chinese hamster ovary cells (CHO-K1) and 1321N1 human astrocytoma cells, and their agonist selectivities and coupling efficiencies to phospholipase C and adenylyl cyclase were assessed. Adenosine triphosphate nucleotides were much more potent and efficacious at the hP2Y11 receptor than their corresponding diphosphates in promoting both inositol phosphate and cyclic AMP accumulation. In contrast, adenosine diphosphate nucleotides were considerably more potent at the cP2Y11 receptor than their corresponding triphosphate analogs. The tri- versus diphosphate specificity of the two receptors was further confirmed in studies using Ca(2+) mobilization as a measure of receptor activation under conditions that minimized nucleotide degradation. Moreover, 2-methylthioadenosine-5'-triphosphate and 2-methylthioadenosine-5'-diphosphate were 58- and 75-fold more potent than ATP and ADP, respectively, at the cP2Y11 receptor compared with only 2- to 3-fold more potent at the hP2Y11 receptor. Mutational analysis revealed that the change of Arg-265, which is located at the juxtaposition of transmembrane domain 6 and the third extracellular loop in the hP2Y11 receptor, to glutamine in the cP2Y11 receptor is at least partly responsible for the diphosphate selectivity but not the increased sensitivity to 2-thioether-substituted adenine nucleotides at the canine receptor. These results imply a key role for a positively charged arginine residue in contributing to the recognition of extracellular nucleotides by the P2Y11 receptor and perhaps other P2Y receptors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1375-82
pubmed:dateRevised
2010-1-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
An arginine/glutamine difference at the juxtaposition of transmembrane domain 6 and the third extracellular loop contributes to the markedly different nucleotide selectivities of human and canine P2Y11 receptors.
pubmed:affiliation
Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599-7365, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't