Linked Life Data

11071711

Source:http://linkedlifedata.com/resource/pubmed/id/11071711

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-12-15
pubmed:abstractText
Previous data obtained with the cloned rat mu opioid receptor demonstrated that stereochemistry affects the four parameters of the ligand-receptor interaction: potency (ED(50)), efficacy (maximal stimulation), intrinsic efficacy (effect as a function of receptor occupation), and binding affinity. This study evaluated the activities of structurally diverse opioid receptor ligands in the [(35)S]GTP-gamma-S binding assay, comparing the relationship between receptor binding, activation, efficacy, and intrinsic efficacy. The data, obtained with cloned rat mu receptors, demonstrated that an analgetic, (-)-5-m-hydroxyphenyl-2-methylmorphan (NIH8508), and its (+)-isomer (NIH8509), behave as partial agonists, but had different intrinsic efficacy in the [(35)S]GTP-gamma-S binding assay. Replacement of the methyl group with the phenethyl group on the piperidine nitrogen of NIH8508 and NIH8509 [(1R,5S)-AH019 and (1S, 5R)-AH019] increased affinity for the mu receptor and eliminated any agonist effect, supporting the hypothesis that certain structural features make these compounds antagonists. These study also show that all of the fully efficacious mu agonists studied here had high levels of intrinsic efficacy, producing a 50% response at about 10% receptor occupancy. Comparison of the binding K(i) in competitively inhibiting [(125)I]IOXY binding to the functional K(i) for opioid antagonists [K(i)(IOXY)/K(i)(GTP-gamma-S)] provides more detailed evidence that the [(35)S]GTP-gamma-S binding assay can be used to reliably determine apparent functional antagonist K(i) values in addition to agonist ED(50), efficacy and intrinsic efficacy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0887-4476
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
64-9
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Opioid peptide receptor studies. 14. Stereochemistry determines agonist efficacy and intrinsic efficacy in the [(35)S]GTP-gamma-S functional binding assay.
pubmed:affiliation
CPS, DIR, NIDA, Baltimore, Maryland 21224, USA.
pubmed:publicationType
Journal Article