Linked Life Data

21036244

Source:http://linkedlifedata.com/resource/pubmed/id/21036244

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-11-1
pubmed:abstractText
Constitutive (basal) signaling has been described and characterized for numerous G protein coupled receptors (GPCRs). The relevance of this activity to disease, drug discovery and development, and to clinical pharmacotherapy is just beginning to emerge. Opioid receptors were the first GPCR systems for which there was definitive evidence presented for constitutive activity, with numerous studies now published on the regulation of this activity (e.g., structure/activity of the receptor as it relates to basal activity, pharmacology of ligands that act as agonists, inverse agonists and "neutral antagonists," etc.). This chapter summarizes some of the methods used to characterize constitutive activity at the mu opioid receptor (MOR) in preclinical in vitro and in vivo model systems. This includes cell-based systems that are useful for higher throughput screening of novel ligands and for studying variables that can impact basal tone in a system. In vivo assays are also described in which constitutive activity is increased in response to acute or chronic opioid agonist exposure and where withdrawal is precipitated with antagonists that may function as inverse agonists or "neutral" antagonists. The methods described have inherent advantages and disadvantages that need to be considered in any drug discovery/development program. A brief discussion of progress toward understanding the clinical implications of MOR constitutive activity in the management of opioid addiction and chronic pain is also included in this chapter.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1557-7988
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
484
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
413-43
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
In vitro and in vivo assessment of mu opioid receptor constitutive activity.
pubmed:affiliation
Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, Maine, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Intramural