Linked Life Data

19785654

Source:http://linkedlifedata.com/resource/pubmed/id/19785654

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-10-28
pubmed:abstractText
BACKGROUND AND PURPOSE: A peptide bradykinin (BK) B(2) receptor agonist partially resistant to degradation, B-9972, down-regulates this receptor subtype. We have used another recently described non-peptide agonist, compound 47a, as a tool to study further the effects of metabolically more stable and thus persistent, agonists of the BK B(2) receptor on signalling, desensitization and down-regulation of this receptor. EXPERIMENTAL APPROACH AND KEY RESULTS: Compound 47a was a partial agonist at the B(2) receptor in the human umbilical vein, where it shared with B-9972 a very slow relaxation on washout, and in HEK 293 cell lines expressing tagged forms [myc, green fluorescent protein (GFP)] of the rabbit B(2) receptor. Compound 47a desensitized the umbilical vein to BK. In the cellular systems, the inactivation-resistant agonists induced [Ca(2+)](i) transients as brief as those of BK but affected other functions with a longer duration than BK [12 h; receptor endocytosis, endosomal beta-arrestin(1/2) translocation, protein kinase C-dependent extracellular signal-regulated kinases (ERK)1/2 phosphorylation and c-Fos expression]. The B(2) receptor-GFP was degraded in cells exposed to B-9972 or compound 47a for 12 h. The non-peptide B(2) receptor antagonist LF 16-0687 prevented all effects of compound 47a, which were also absent in cells lacking recombinant B(2) receptors. CONCLUSION AND IMPLICATIONS: Inactivation-resistant agonists revealed a long-lasting assembly of the agonist-B(2) receptor-beta-arrestin complexes in endosomal structures and induce 'biased signalling' (in terms of activation of ERK and c-Fos) as a function of time. Further, B-9972 and compound 47a, unlike BK, efficiently down-regulated BK B(2) receptors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1476-5381
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
158
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1375-86
pubmed:dateRevised
2010-11-2
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Effects of inactivation-resistant agonists on the signalling, desensitization and down-regulation of bradykinin B(2) receptors.
pubmed:affiliation
Centre de recherche en rhumatologie et immunologie, Centre Hospitalier Universitaire de Québec and Department of Medicine, Université Laval, Québec, QC, Canada.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't