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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1989-3-28
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pubmed:abstractText |
Using biochemical and patch-clamp techniques, we investigated the pharmacology of S- and R-epimers of N-methylanatoxinol, which are analogs of the semi-rigid, stereoselective, nicotinic agonist (+)-anatoxin-a. In contrast to (+)-anatoxin-a, both isomers had poor ability to inhibit the binding of 125I-alpha-bungarotoxin or to open acetylcholine channels, and they were unable to elicit contracture of frog rectus abdominis muscles. However, both isomers were able to demonstrate significant concentration-dependent blockade of the nicotinic acetylcholine receptor ion channel. The R-isomer was approximately 4-fold more potent in causing inhibition of [3H]H12HTX binding than was the S-isomer, in the absence of carbamylcholine. In the presence of carbamylcholine, the affinity of the R-isomer of N-methylanatoxinol for the ion channel sites was further enhanced, so that its affinity became much greater than that of the S-isomer. Refinement of voltage- and concentration-dependent terms for the ion channel blocking and unblocking rates yielded functions that were able to predict the channel open times and short closed times well. The S-isomer bound and dissociated from the ion channel site of the nicotinic acetylcholine receptor more rapidly and with greater voltage sensitivity than the R-isomer. The present characterization of the antagonistic properties of these new analogs of (+)-anatoxin-a introduces a new aspect to the molecular pharmacology of (+)-anatoxin-a analogs; the semi-rigid compounds could be useful in describing the allosteric binding sites of the acetylcholine receptor, as well as in delimiting the agonist binding site.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/Bicyclo Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Bicyclo Compounds, Heterocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Bridged Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Ion Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Marine Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/Microcystins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nicotinic,
http://linkedlifedata.com/resource/pubmed/chemical/Tropanes,
http://linkedlifedata.com/resource/pubmed/chemical/anatoxin a,
http://linkedlifedata.com/resource/pubmed/chemical/cyanobacterial toxin
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
223-31
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:2465486-Animals,
pubmed-meshheading:2465486-Bacterial Toxins,
pubmed-meshheading:2465486-Bicyclo Compounds,
pubmed-meshheading:2465486-Bicyclo Compounds, Heterocyclic,
pubmed-meshheading:2465486-Binding Sites,
pubmed-meshheading:2465486-Bridged Compounds,
pubmed-meshheading:2465486-Dose-Response Relationship, Drug,
pubmed-meshheading:2465486-Ion Channels,
pubmed-meshheading:2465486-Marine Toxins,
pubmed-meshheading:2465486-Microcystins,
pubmed-meshheading:2465486-Muscle Contraction,
pubmed-meshheading:2465486-Rana pipiens,
pubmed-meshheading:2465486-Receptors, Nicotinic,
pubmed-meshheading:2465486-Stereoisomerism,
pubmed-meshheading:2465486-Structure-Activity Relationship,
pubmed-meshheading:2465486-Tropanes
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pubmed:year |
1989
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pubmed:articleTitle |
N-methylanatoxinol isomers: derivatives of the agonist (+)-anatoxin-a block the nicotinic acetylcholine receptor ion channel.
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pubmed:affiliation |
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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