Linked Life Data

15610819

Source:http://linkedlifedata.com/resource/pubmed/id/15610819

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-12-21
pubmed:abstractText
Resistance of parasitic nematodes to the cholinergic anthelmintic levamisole is associated with a reduction in the proportion of time that acetylcholine receptor ion-channels are in the open state decreasing the response of nematode parasites to the drug. Here we examine electrophysiological and contractile responses to acetylcholine and the cholinergic agonist, levamisole, in Ascaris suum muscle looking for a pharmacological approach that may be developed to increase the response to cholinergic agonists. We found that short application of the FMRFamide, AF2, produced modulation (long lasting potentiation) of the peak membrane potential response to acetylcholine but not to levamisole. Since levamisole preferentially activates L-type acetylcholine receptors, we also tested the effect of nicotine (selective activator of N-type acetylcholine receptors) and bephenium (selective activator of B-type acetylcholine receptors) and found again no effect of AF2 on peak membrane potential responses. We then tested atropine on the AF2 potentiation of acetylcholine and found it to inhibit the peak potentiation suggesting that AF2 receptors interact with muscarinic receptors to produce the potentiation of acetylcholine. We saw similar atropine sensitive potentiation of acetylcholine responses in our muscle contraction experiments. The potentiation of the acetylcholine responses shows that nematode acetylcholine receptors are capable of a level of plasticity. A model involving calcium release from the sarcoplasmic reticulum, CaM Kinase, calcineurin, muscarinic receptors and AF2 receptors is proposed to explain our observations. These observations are important because they point to a pharmacological approach that may be developed to counter resistance to cholinergic anthelmintics.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0166-6851
pubmed:author
pubmed:issnType
Print
pubmed:volume
139
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
51-64
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Brief application of AF2 produces long lasting potentiation of nAChR responses in Ascaris suum.
pubmed:affiliation
Department of Biomedical Sciences, Iowa State University, Ames, IA 50010, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural