Linked Life Data

1318093

Source:http://linkedlifedata.com/resource/pubmed/id/1318093

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1992-7-16
pubmed:abstractText
The "membrane bilayer" pathway (Rhodes, D. G., J. G. Sarmiento, and L. G. Herbette. 1985. Mol. Pharmacol. 27:612-623.) for 1,4-dihydropyridine calcium channel drug (DHP) binding to receptor sites in cardiac sarcolemmal membranes has been extended to include the interaction of amphiphiles within the lipid bilayer. These studies focused on the ability of the Class III antiarrhythmic agents bretylium and clofilium to nonspecifically inhibit DHP-receptor binding in canine cardiac sarcolemma. Clofilium was found to inhibit nimodipine binding with an inhibition constant of approximately 5 microM, whereas bretylium had no effect on nimodipine binding. Small angle x-ray diffraction was then used to examine the differential ability of these two Class III agents to inhibit DHP-receptor binding. The time-averaged locations of bretylium, clofilium, and nimodipine in bovine cardiac phosphatidylcholine (BCPC) bilayers (supplemented with 13 mol% cholesterol) were determined to a resolution of 9 A. The location of bretylium as dominated by its phenyl ring in BCPC bilayers was found to be at the hydrocarbon core/water interface, similar to that of the dihydropyridine ring of nimodipine. The location of clofilium as dominated by its phenyl ring was found to be below the hydrocarbon/core water interface within the hydrocarbon chain region of the bilayer, similar to that of the phenyl ring of nimodipine. The location of the dihydropyridine ring portion of nimodipine has previously been shown by neutron diffraction to be located at the hydrocarbon core/water interface of native sarcoplasmic reticulum, consistent with the small angle x-ray data from model membranes in this paper. Therefore, we speculate that the nonspecific inhibition arises from the interaction of clofilium's phenyl ring with the site on the calcium channel receptor where the phenyl ring portion of nimodipine must interact. The DHP-receptor binding pathway would then involve both nonspecific (membrane) and specific (protein) binding components, both of which are necessary for receptor binding.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-14069237, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-1689708, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-1910441, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-19431663, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-2413915, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-2447967, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-2470429, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-2872689, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-2987659, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-3001105, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-300786, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-3207838, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-3970900, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-5859039, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-6205402, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-6253461, http://linkedlifedata.com/resource/pubmed/commentcorrection/1318093-6300912
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-3495
pubmed:author
pubmed:issnType
Print
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1244-55
pubmed:dateRevised
2010-9-7
pubmed:meshHeading
pubmed-meshheading:1318093-Animals, pubmed-meshheading:1318093-Binding, Competitive, pubmed-meshheading:1318093-Binding Sites, pubmed-meshheading:1318093-Biophysical Phenomena, pubmed-meshheading:1318093-Biophysics, pubmed-meshheading:1318093-Bretylium Compounds, pubmed-meshheading:1318093-Calcium Channel Blockers, pubmed-meshheading:1318093-Calcium Channels, pubmed-meshheading:1318093-Dogs, pubmed-meshheading:1318093-Lipid Bilayers, pubmed-meshheading:1318093-Models, Molecular, pubmed-meshheading:1318093-Myocardium, pubmed-meshheading:1318093-Nicotinic Antagonists, pubmed-meshheading:1318093-Nimodipine, pubmed-meshheading:1318093-Quaternary Ammonium Compounds, pubmed-meshheading:1318093-Receptors, Nicotinic, pubmed-meshheading:1318093-Sarcolemma, pubmed-meshheading:1318093-X-Ray Diffraction
pubmed:year
1992
pubmed:articleTitle
Molecular basis for the inhibition of 1,4-dihydropyridine calcium channel drugs binding to their receptors by a nonspecific site interaction mechanism.
pubmed:affiliation
Department of Biochemistry, University of Connecticut, Farmington 06030-2017.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't