Linked Life Data

10220565

Source:http://linkedlifedata.com/resource/pubmed/id/10220565

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-6-1
pubmed:abstractText
In cell systems where ligand-independent receptor activity is optimized (such as when receptors are overexpressed or mutated), acute treatment with inverse agonists reduces basal effector activity whereas prolonged exposure leads to sensitization of receptor systems and receptor up-regulation. Few studies, however, have reported effects of inverse agonists in systems where nonmutated receptors are expressed at relatively low density. Here, we investigated the effects of inverse agonists at human serotonin (5-HT)2C receptors expressed stably in Chinese hamster ovary cells ( approximately 250 fmol/mg protein). In these cells, there is no receptor reserve for 5-HT and 5-HT2C inverse agonists did not reduce basal inositol phosphate (IP) accumulation nor arachidonic acid (AA) release but behaved as simple competitive antagonists, suggesting that these receptors are not overexpressed. Prolonged treatment (24 h) with inverse agonists enhanced selectively 5-HT2C-mediated IP accumulation but not AA release. The enhancing effect occurred within 4 h of treatment, reversed within 3 to 4 h (after 24-h treatment), and could be blocked with neutral antagonists or weak positive agonists. The enhanced responsiveness was not due to receptor up-regulation but may involve changes in the expression of the G protein, Galphaq/11 and possibly Galpha12 and Galpha13. Interestingly, 24-h exposure to inverse agonists acting at 5-HT2C receptors also selectively enhanced IP accumulation, but not AA release, elicited by activation of endogenous purinergic receptors. These data suggest that actions of inverse agonists may be mediated through effects on receptor systems that are not direct targets for these drugs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
863-72
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Novel actions of inverse agonists on 5-HT2C receptor systems.
pubmed:affiliation
Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78284-7764, USA. berg@uthascsa.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.