Linked Life Data

15795101

Source:http://linkedlifedata.com/resource/pubmed/id/15795101

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-3-29
pubmed:abstractText
Passive uptake of drugs into cells is described in terms of the following steps: (1) massive immediate binding of the drugs to the outer leaflet of the plasma membrane resulting in practical equilibrium between extremely high drug concentrations at the cell surface compared to the drug concentration in the medium. (2) Due to their amphipathic nature, anticancer drugs are practically excluded from the lipid core of the membrane. They cross the lipid core by distinct flip-flop events that occur in the case of doxorubicin and daunorubicin after an average period of 0.7 and 0.15 min, respectively. (3) The drug reaching the inner leaflet of the plasma membrane is in practical equilibrium with the drug present in the cytoplasm. (4) Almost all the amounts of anticancer drugs present in the cells are bound by molecular sinks, such as DNA or cytoskeleton elements. The resistance afforded to multidrug resistant (MDR) cells by extrusion pumps, such as P-glycoprotein, is negatively correlated with the affinity of the drugs to the membranes and with their flip-flop rates across membranes. Binding rates of the drugs to membranes and intracellular sinks have no effect on drug concentration in the cytoplasm once equilibrium is reached between the passive uptake of drugs and their active extrusion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0753-3322
pubmed:author
pubmed:issnType
Print
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
90-7
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Mechanism of multidrug resistance in relation to passive membrane permeation.
pubmed:affiliation
Department of Biology, Technion, Israel Institute of Technology, Haifa 32000, Israel. eytan@tx.technion.ac.il
pubmed:publicationType
Journal Article, Review