Linked Life Data

6693422

Source:http://linkedlifedata.com/resource/pubmed/id/6693422

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1984-3-16
pubmed:abstractText
Routes which contribute to the transport of methotrexate across the plasma membrane of L1210 cells have been evaluated. A single high affinity transport system was found to be the only route for methotrexate uptake. This conclusion was derived from the observations that influx at high substrate concentrations (up to 50 microM) both reaches a single maximum value and can be inhibited by greater than 98% either by treatment of the cells with an active ester of methotrexate or by the direct addition of excess amounts of competitive inhibitors. Efflux, conversely, could be separated into three components. One of these routes was dependent upon extracellular anions and could be blocked by active ester treatment and, therefore, appeared to be the same transport system which mediates methotrexate influx. A second route was identified by its sensitivity to bromosulfophthalein, while a third component was insensitive to both active ester treatment and to bromosulfophthalein. When these efflux routes were quantitated in a buffered saline medium, the methotrexate influx carrier was found to account for the major portion (71%) of total efflux. The inhibitor-insensitive component contributed an additional 23%, while the remaining 6% was attributable to the bromosulfophthalein-sensitive route. The addition of glucose increased total efflux by 3-fold and caused a substantial change in the proportion of efflux that occurred via each of the three components. The major portion of efflux (46%) now occurred via the bromosulfophthalein-sensitive route, while the influx carrier contributed only 29% of the total. The inhibitor-insensitive route accounted for the remaining 25%. The opposite result was obtained with metabolic inhibitors which decreased total efflux but increased the contribution by the influx carrier to greater than 80%. The demonstration of multiple routes for methotrexate efflux and their differential sensitivities to alterations in energy metabolism thus provides a basis for explaining previously described asymmetries between the influx and efflux of methotrexate in mouse leukemia cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
259
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1526-31
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Transport routes utilized by L1210 cells for the influx and efflux of methotrexate.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't