Linked Life Data

10565838

Source:http://linkedlifedata.com/resource/pubmed/id/10565838

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-12-20
pubmed:abstractText
Benzodiazepines, a class of drugs commonly used to induce anesthesia and sedation, can attenuate intracellular calcium oscillations evoked by alpha(1)-adrenergic receptor (alpha(1)-AR) stimulation in pulmonary artery smooth muscle cells. We postulated a direct action of benzodiazepines in modulating alpha(1)-AR function at the receptor level. Benzodiazepines bound to each of the cloned alpha(1)-AR subtypes (alpha(1a)-, alpha(1b)-, or alpha(1d)-AR) on COS-1 cell membranes transiently transfected to express a single population of alpha(1)-AR subtype. The ability of benzodiazepines to alter alpha(1)-AR signal transduction was investigated by measuring total inositol phosphate generation in rat-1 fibroblast cells, stably transfected to express a single alpha(1)-AR subtype. By themselves, benzodiazepines displayed partial agonism. At alpha(1b)-ARs and alpha(1d)-ARs, the maximal inositol phosphate response to phenylephrine was potentiated almost 2-fold by either midazolam or lorazepam (100 microM). At alpha(1a)-ARs, diazepam, lorazepam, and midazolam all increased the maximal response of the partial agonist clonidine at these receptors, whereas the response to the full agonist phenylephrine was unaltered or inhibited. The potentiating actions of midazolam and its partial agonism at alpha(1)-ARs was blocked by the addition of 1 microM prazosin, an alpha(1)-AR antagonist, and not by a gamma-aminobutyric acid(A)-receptor antagonist. These studies show that benzodiazepines modulate the function of alpha(1)-ARs in vitro, and this is the first report of a potential allosteric site on alpha(1)-ARs that may be therapeutically useful for drug design.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
291
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1164-71
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10565838-Adrenergic alpha-Agonists, pubmed-meshheading:10565838-Adrenergic alpha-Antagonists, pubmed-meshheading:10565838-Animals, pubmed-meshheading:10565838-Benzodiazepines, pubmed-meshheading:10565838-COS Cells, pubmed-meshheading:10565838-Cell Membrane, pubmed-meshheading:10565838-Cells, Cultured, pubmed-meshheading:10565838-Drug Synergism, pubmed-meshheading:10565838-Epinephrine, pubmed-meshheading:10565838-Fibroblasts, pubmed-meshheading:10565838-Inositol Phosphates, pubmed-meshheading:10565838-Ligands, pubmed-meshheading:10565838-Molecular Conformation, pubmed-meshheading:10565838-Phenylephrine, pubmed-meshheading:10565838-Radioligand Assay, pubmed-meshheading:10565838-Rats, pubmed-meshheading:10565838-Receptors, Adrenergic, alpha-1, pubmed-meshheading:10565838-Signal Transduction, pubmed-meshheading:10565838-Transfection
pubmed:year
1999
pubmed:articleTitle
Binding, partial agonism, and potentiation of alpha(1)-adrenergic receptor function by benzodiazepines: A potential site of allosteric modulation.
pubmed:affiliation
Department of Molecular Cardiology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't