Linked Life Data

9514944

Source:http://linkedlifedata.com/resource/pubmed/id/9514944

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-4-23
pubmed:abstractText
The multidrug resistance (MDR)-associated P-glycoprotein (P-gp) is a membrane transporter which carries, at the expense of MgATP hydrolysis, many amphiphilic molecules, such as the MDR-related cytotoxic drugs vincristine and vinblastine, and the MDR-reversing agents verapamil and progesterone. We have tested the effects on P-gp function of bromocriptine (BCT), an ergot alkaloid known as a D2 dopaminergic receptor agonist. BCT (at 4 microM) partially reverses the P-gp-mediated vincristine resistance of the Chinese hamster lung fibroblasts DC-3F/ADX, a MDR cell line. P-gp containing membrane vesicles prepared from the DC-3F/ADX cells exhibit, in the absence of any added drug, a basal MgATPase activity due to P-gp. BCT inhibits this basal ATPase activity, with a half-inhibiting concentration of 0.30 +/- 0.15 microM. BCT also inhibits the verapamil-induced P-gp ATPase stimulation competitively (Ki approximately 0.2 microM), and the progesterone-induced P-gp ATPase stimulation non-competitively (Ki approximately 0.07-0.10 microM). BCT also non-competitively inhibits the vinblastine-dependent P-gp ATPase activity within the same concentration range. Hydroxylated metabolites of BCT have different effects on P-gp ATPase, only the monohydroxylated being able to modulate both the basal and the drug-stimulated ATPase activities. In conclusion, these effects of BCT on P-gp function can be linked to a specific interaction with P-gp, probably involving inhibition of P-gp-mediated drug transport.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
244
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
481-8
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Bromocriptine modulates P-glycoprotein function.
pubmed:affiliation
Section de Biophysique des Protéines et des Membranes, DBCM, CEA, Centre d'Etudes de Saclay, Gif/Yvette, France. orlowski@dsvidf.cea.fr
pubmed:publicationType
Journal Article