Linked Life Data

17152090

Source:http://linkedlifedata.com/resource/pubmed/id/17152090

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-1-9
pubmed:abstractText
Previous studies established that Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO) and (2S,4aR,6aR,7R,9S,10aS,10bR)-9-(Benzoyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester (herkinorin) are fully efficacious mu-agonists. Herkinorin (HERK), unlike DAMGO, does not recruit beta-arrestin and promote mu-receptor internalization, even in cells that over express beta-arrestin. We hypothesized that chronic HERK and DAMGO treatment will differentially affect cellular markers of tolerance and dependence. CHO cells expressing the cloned human mu-receptor were treated for 20 h with 10 microM DAMGO, HERK, morphine, or medium. Both DAMGO and HERK acted as full agonists in the [(35)S]GTP-gamma-S binding assay with E(MAX) values of 230% and EC(50) values of 12.8 and 92.5 nM, respectively. In the cAMP assay, DAMGO and HERK had similar E(MAX) values of approximately 80% and EC(50) values of 3.23 and 48.7 nM, respectively. Chronic exposure to both drugs produced moderate tolerance to both drugs ( approximately 2 to 5 fold) in the [(35)S]GTP-gamma-S binding assay. In the cAMP assay, chronic DAMGO produced tolerance to both drugs ( approximately 3 to 4 fold). Chronic HERK eliminated the ability of either drug to inhibit forskolin-stimulated cAMP accumulation. Chronic DAMGO increased, and chronic HERK decreased, forskolin-stimulated cAMP accumulation. Naloxone, after chronic HERK (but not DAMGO) induced a large increase in forskolin-stimulated cAMP accumulation. Viewed collectively with published data, the current data indicate that both internalizing and noninternalizing mu-agonists produce cellular signs of tolerance and dependence.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0887-4476
pubmed:author
pubmed:issnType
Print
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
166-75
pubmed:dateRevised
2010-8-9
pubmed:meshHeading
pubmed-meshheading:17152090-Analgesics, Opioid, pubmed-meshheading:17152090-Animals, pubmed-meshheading:17152090-Binding, Competitive, pubmed-meshheading:17152090-CHO Cells, pubmed-meshheading:17152090-Cell Membrane, pubmed-meshheading:17152090-Cricetinae, pubmed-meshheading:17152090-Cricetulus, pubmed-meshheading:17152090-Cyclic AMP, pubmed-meshheading:17152090-Drug Tolerance, pubmed-meshheading:17152090-Endocytosis, pubmed-meshheading:17152090-Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, pubmed-meshheading:17152090-Forskolin, pubmed-meshheading:17152090-Furans, pubmed-meshheading:17152090-Guanosine 5'-O-(3-Thiotriphosphate), pubmed-meshheading:17152090-Humans, pubmed-meshheading:17152090-Narcotic Antagonists, pubmed-meshheading:17152090-Opioid-Related Disorders, pubmed-meshheading:17152090-Pyrones, pubmed-meshheading:17152090-Radioligand Assay, pubmed-meshheading:17152090-Receptors, Opioid, mu
pubmed:year
2007
pubmed:articleTitle
A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence.
pubmed:affiliation
Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, DHHS, Baltimore, Maryland 21224, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural