Linked Life Data

10071788

Source:http://linkedlifedata.com/resource/pubmed/id/10071788

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-4
pubmed:dateCreated
1999-6-15
pubmed:abstractText
Substances eliciting, at very high concentrations, a lower maximal response of a particular biological system than a defined standard, are defined as partial agonists. The convention rests on the definition of a standard substance that achieves a 'full' maximal response; partial agonism being, therefore, relative. Various mechanisms lie behind this phenomenon: 1. Receptor-related mechanisms: the agonist-receptor complex exists in several conformational states from which only one, or only a few, activate the cell signaling pathway. This may occur when the receptor itself, or the agonist, exists in multiple states (e.g., in the form of enantiomers or stereoisomers), or when the agonist-receptor complex changes its conformation (receptor switch: two-state model of receptor activation). Furthermore, a steric hindrance by a 'wrong-way binding' of a part of the agonist's molecules may prevent the full 'correct' occupancy of receptors. 2. Mechanisms based on the efficacy of the stimulus-response coupling. The efficacy is then proportional to the sum of probabilities that receptors in individual states activate the cell-signaling pathway. Doses (concentrations) eliciting the half maximal response (EC50), or similar response sensitivity parameters, are not included in the definition of partial agonism. However, tight correlations exist between maximal response and EC50 in many, but not all, generic groups of agonistically acting substances. These relationships are frequently linear; intercepts and slopes of these 'E, KE plots' are characteristic for individual, putative mechanisms. Dose-response curves of partial agonists are akin to those obtained for a response to a full agonist after a stepwise partial inactivation of receptors by an irreversible inhibitor. Also, the E, KE plots obtained in these instances are similar to those of partial agonists. The receptor reserve, rather vaguely defined in early reports, is therefore closely linked to the phenomenon of partial agonism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1079-9893
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
597-629
pubmed:dateRevised
2005-11-16
pubmed:meshHeading
pubmed:articleTitle
Partial agonism: mechanisms based on ligand-receptor interactions and on stimulus-response coupling.
pubmed:affiliation
Department of Animal Science, ETH-Swiss Federal Institute of Technology, Zürich, Switzerland.
pubmed:publicationType
Journal Article, Review