Linked Life Data

12519790

Source:http://linkedlifedata.com/resource/pubmed/id/12519790

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2003-3-10
pubmed:abstractText
Agonist exposure of many G protein-coupled receptors induces a rapid receptor phosphorylation and uncoupling from G proteins. Resensitization of these desensitized receptors requires endocytosis and subsequent dephosphorylation. Using a yeast two-hybrid screen, the rat mu-opioid receptor (MOR1, also termed MOP) was found to be associated with phospholipase D2 (PLD2), a phospholipid-specific phosphodiesterase located in the plasma membrane, which has been implicated in the formation of endocytotic vesicles. Coimmunoprecipitation experiments in HEK293 cells coexpressing MOR1 and PLD2 confirmed that MOR1 constitutively interacts with PLD2. Treatment with the mu receptor agonist DAMGO ([d-Ala(2), Me Phe(4), Glyol(5)]enkephalin) led to an increase in PLD2 activity, whereas morphine, which does not induce MOR1 receptor internalization, failed to induce PLD2 activation. The DAMGO-mediated PLD2 activation was inhibited by brefeldin A, an inhibitor of ADP-ribosylation factor (ARF) but not by the protein kinase C (PKC) inhibitor calphostin C indicating that opioid receptor-mediated activation of PLD2 is ARF- but not PKC-dependent. Furthermore, heterologous stimulation of PLD2 by phorbol ester led to an accelerated internalization of the mu-opioid receptor after both DAMGO and morphine exposure. Conversely the inhibition of PLD2-mediated phosphatidic acid formation by 1-butanol or overexpression of a negative mutant of PLD2 prevented agonist-mediated endocytosis of MOR1. Together, these data suggest that PLD2 play a key role in the regulation of agonist-induced endocytosis of the mu-opioid receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9979-85
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12519790-1-Butanol, pubmed-meshheading:12519790-ADP-Ribosylation Factors, pubmed-meshheading:12519790-Animals, pubmed-meshheading:12519790-Cell Line, pubmed-meshheading:12519790-Cell Membrane, pubmed-meshheading:12519790-Cloning, Molecular, pubmed-meshheading:12519790-DNA, Complementary, pubmed-meshheading:12519790-Dose-Response Relationship, Drug, pubmed-meshheading:12519790-Endocytosis, pubmed-meshheading:12519790-Enzyme Activation, pubmed-meshheading:12519790-Epitopes, pubmed-meshheading:12519790-Humans, pubmed-meshheading:12519790-Immunoblotting, pubmed-meshheading:12519790-Microscopy, Confocal, pubmed-meshheading:12519790-Morphine, pubmed-meshheading:12519790-Mutation, pubmed-meshheading:12519790-Phospholipase D, pubmed-meshheading:12519790-Precipitin Tests, pubmed-meshheading:12519790-Protein Binding, pubmed-meshheading:12519790-Protein Structure, Tertiary, pubmed-meshheading:12519790-Rats, pubmed-meshheading:12519790-Receptors, Opioid, mu, pubmed-meshheading:12519790-Time Factors, pubmed-meshheading:12519790-Two-Hybrid System Techniques
pubmed:year
2003
pubmed:articleTitle
ADP-ribosylation factor-dependent phospholipase D2 activation is required for agonist-induced mu-opioid receptor endocytosis.
pubmed:affiliation
Department of Pharmacology and Toxicology, Otto-von-Guericke University, 39120 Magdeburg, Germany. Thomas.Koch@Medizin.Uni-Magdeburg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't