Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-10-30
pubmed:abstractText
Using Xenopus laevis oocytes coexpressing mammalian mu-opioid receptors (MORs), beta-adrenergic receptor kinase 2 (beta-ARK2) [also called G protein-coupled receptor kinase (GRK3)], and beta-arrestin 2 (beta-arr 2), we compared the rates of beta-ARK2 (GRK3)- and beta-arr 2-mediated homologous receptor desensitization produced by treatment with opioid agonists of different efficacies. The response to MOR activation was measured using two-electrode voltage clamp as an increase in the conductance of the coexpressed G protein-coupled inwardly rectifying potassium (heteromultimer of KIR3.1 and KIR3.4) channels. Treatment with opioids of high efficacy, either [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin, fentanyl, or sufentanyl, produced a GRK3- and beta-arr 2-dependent reduction in response in <20 min, whereas treatment with the partial agonist morphine produced receptor desensitization at a significantly slower rate. Because GRK3 requires activation and membrane targeting by free G protein betagamma subunits released after agonist-mediated activation of G proteins, a low efficacy agonist such as morphine may produce weak receptor desensitization as a consequence of poor GRK3 activation. To address this hypothesis, we substituted GRK5, a GRK that does not require activation by G protein betagamma. In oocytes expressing GRK5 instead of GRK3, both [D-Ala2,N-MePhe4, Gly-ol5]enkephalin and fentanyl, but not morphine, produced desensitization of MOR-activated potassium conductance. Thus, mu-opioid agonists produced significant receptor desensitization, mediated by either GRK3 or GRK5, at a rate dependent on agonist efficacy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/ADRBK2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Adrbk2 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Analgesics, Opioid, http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, http://linkedlifedata.com/resource/pubmed/chemical/Enkephalins, http://linkedlifedata.com/resource/pubmed/chemical/Fentanyl, http://linkedlifedata.com/resource/pubmed/chemical/G-Protein-Coupled Receptor Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/G-Protein-Coupled Receptor Kinase 5, http://linkedlifedata.com/resource/pubmed/chemical/GRK5 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Gprk5 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Morphine, http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, mu
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
704-11
pubmed:dateRevised
2011-1-19
pubmed:meshHeading
pubmed-meshheading:9765514-Analgesics, Opioid, pubmed-meshheading:9765514-Animals, pubmed-meshheading:9765514-Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, pubmed-meshheading:9765514-Enkephalins, pubmed-meshheading:9765514-Fentanyl, pubmed-meshheading:9765514-G-Protein-Coupled Receptor Kinase 3, pubmed-meshheading:9765514-G-Protein-Coupled Receptor Kinase 5, pubmed-meshheading:9765514-Humans, pubmed-meshheading:9765514-Kinetics, pubmed-meshheading:9765514-Morphine, pubmed-meshheading:9765514-Potassium Channels, pubmed-meshheading:9765514-Protein-Serine-Threonine Kinases, pubmed-meshheading:9765514-Rats, pubmed-meshheading:9765514-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:9765514-Receptors, Opioid, mu, pubmed-meshheading:9765514-Sensitivity and Specificity, pubmed-meshheading:9765514-Xenopus laevis
pubmed:year
1998
pubmed:articleTitle
Agonist induced homologous desensitization of mu-opioid receptors mediated by G protein-coupled receptor kinases is dependent on agonist efficacy.
pubmed:affiliation
Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.