Linked Life Data

12119452

Source:http://linkedlifedata.com/resource/pubmed/id/12119452

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-7-16
pubmed:abstractText
In the course of examining the actions of major human bile acids on cholinergic receptors, we discovered that conjugates of lithocholic acid are partial muscarinic agonists. In the present communication, we report that conjugates of deoxycholic acid (DC) act as cholinergic muscarinic receptor antagonists. Chinese hamster ovary (CHO) cells expressing rat M3-muscarinic receptors were used to test bile acids for inhibition of radioligand [N- (3)H-methylscopolamine ((3)H-NMS)] binding; alteration of inositol phosphate (IP) formation; mitogen-activated protein (MAP) kinase phosphorylation and cell toxicity. We observed approximately 18.8, 30.3 and 37.1% inhibition of (3)H-NMS binding with DC and its glycine (DCG) and taurine (DCT) conjugates, respectively (all 100 micromol/l, p < 0.01). DCT and DCG inhibited acetylcholine-induced increases in IP formation and MAP kinase phosphorylation (p44 and p42 ERK). DCG and DCT did not alter trypan blue exclusion or lactate dehydrogenase release from CHO-M3 cells. We observed the following rank order of potency (IC(50) micromol/l) for inhibition of (3)H-NMS by muscarinic antagonists and bile acids: NMS (0.0004) > 4-DAMP (0.009) > atropine (0.012) > DCT (170) > DCG (250). None of the bile acids tested were hydrolyzed by recombinant cholinesterase. At concentrations achieved in human bile, DC derivatives are natural muscarinic antagonists.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0031-7012
pubmed:author
pubmed:copyrightInfo
Copyright 2002 S. Karger AG, Basel
pubmed:issnType
Print
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
215-21
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12119452-Animals, pubmed-meshheading:12119452-Bile Acids and Salts, pubmed-meshheading:12119452-CHO Cells, pubmed-meshheading:12119452-Cell Membrane, pubmed-meshheading:12119452-Cholinergic Agonists, pubmed-meshheading:12119452-Cholinesterases, pubmed-meshheading:12119452-Cricetinae, pubmed-meshheading:12119452-Deoxycholic Acid, pubmed-meshheading:12119452-Dose-Response Relationship, Drug, pubmed-meshheading:12119452-Female, pubmed-meshheading:12119452-Glycine, pubmed-meshheading:12119452-Humans, pubmed-meshheading:12119452-Inositol Phosphates, pubmed-meshheading:12119452-Mitogen-Activated Protein Kinases, pubmed-meshheading:12119452-Muscarinic Antagonists, pubmed-meshheading:12119452-Phosphorylation, pubmed-meshheading:12119452-Radioligand Assay, pubmed-meshheading:12119452-Rats, pubmed-meshheading:12119452-Receptor, Muscarinic M3, pubmed-meshheading:12119452-Receptors, Muscarinic, pubmed-meshheading:12119452-Taurine
pubmed:year
2002
pubmed:articleTitle
Deoxycholic acid conjugates are muscarinic cholinergic receptor antagonists.
pubmed:affiliation
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, Ark. 72205-7199, USA. raufmanjeanpierre@uams.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S.