Linked Life Data

1983720

Source:http://linkedlifedata.com/resource/pubmed/id/1983720

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1992-4-28
pubmed:abstractText
Multidrug resistance (MDR) genes encode a family of membrane glycoproteins of approximately 170 kD (P-glycoproteins). In man and mouse, the MDR 1 (mdr 1) genes confer resistance to relatively hydrophobic cationic anti-cancer drugs (i.e., vinblastin, adriamycin). Anti-cancer drug sensitivity is restored by addition of other drugs (i.e., verapamil, reserpine) which are also P-glycoprotein substrates. Transfection of MDR 1 genes produces the resistance phenotype and overexpression of P-glycoprotein. Parenchymal cells in several normal tissues express P-glycoprotein in the secretory domain of the plasma membrane (i.e., bile canaliculus of hepatocytes, brush border of proximal tubular, and small intestinal cells). Studies using plasma membrane vesicles of different sidedness derived from the bile canaliculus and small intestinal brush border permit characterization of P-glycoprotein as a unidirectional, temperature dependent, saturable, ATP-dependent transporter which is competitively inhibited by various anti-cancer drugs and other compounds. Transport studies using single cell fluorescence microscopy with image analysis confirm observations in vesicles. No natural substrate has been identified. Structural studies indicate that the requirements for substrates are molecular weight of 350 to 100, hydrophobicity, two planar rings, and a weak cationic charge. Alternative mechanisms of transport function are considered. The identity of P-glycoproteins in normal rat and human tissues has not been established. Antibody reactions suggest that they may belong to the MDR 2 or 3 class. Studies using everted gut sacs suggest that inhibition of P-glycoprotein may facilitate accumulation of anti-cancer drugs in the tissue.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:author
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
229-39
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Structure and function of P-glycoprotein in the normal liver and intestine.
pubmed:affiliation
Department of Physiology, Tufts University School of Medicine, Boston, Massaschusetts 02111.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review