Linked Life Data

3385635

Source:http://linkedlifedata.com/resource/pubmed/id/3385635

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1988-7-29
pubmed:abstractText
The mode of action of ICI 169,369, a novel 5-hydroxytryptamine2 (5-HT2) receptor antagonist, was investigated in arterial muscle. Isolated preparations from calf coronary artery and from rat tail artery with the endothelium rubbed off were set up to contract isometrically with 5-HT. ICI 169,369 (1-3000 nM) antagonized surmountably and competitively the contractile effects of 5-HT in coronary artery (pKB, 9.1) and tail artery (pKB, 8.8). Methysergide antagonized unsurmountably 5-HT-induced contractions by reducing maximum effects to 25% (coronary artery: pIC50, 9.8) and 60% (tail artery: pIC80, 9.0). ICI 169,369 (100-300 nM) restored the maximum effects of 5-HT that had been depressed by methysergide (20 nM coronary artery, 100 nM tail artery). Preincubation with ICI 169,369 also prevented the methysergide-induced depression of the maximum effects of 5-HT. The protective effect of ICI 169,369 was overcome by high methysergide concentrations (up to 3 microM), suggesting competition between the two drugs for a common site. The data are consistent with an allosterically modulated interconversion of the 5-HT2 receptor between two states (R in equilibrium R'). ICI 169,369 competes with 5-HT for the 5-HT2 receptor. ICI 169,369 and methysergide also compete for an allosteric site of the 5-HT2 receptor system, thereby facilitating the highly active R-state and low active R'-state, respectively.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
245
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1010-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
ICI 169,369 is both a competitive antagonist and an allosteric activator of the arterial 5-hydroxytryptamine2 receptor system.
pubmed:affiliation
ICI Pharmaceutical Division, Cheshire, United Kingdom.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't