Linked Life Data

7714780

Source:http://linkedlifedata.com/resource/pubmed/id/7714780

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-5-17
pubmed:abstractText
When the blood-brain barrier (BBB) transport of a series of model peptides that varied in their physicochemical properties (lipophilicity, size and hydrogen-bonding potential) was determined using an in situ rat brain perfusion technique, an unexpected increase in flux with increasing peptide concentration was observed with one of the peptides. Further, inclusion of verapamil in the perfusion medium also increased permeability of the peptides. These observations were consistent with the presence of a polarized efflux system in the BBB that was saturable, could be competitively inhibited and showed substrate specificity. Such properties are similar to those of P-glycoprotein (P-gp), an apically localized efflux pump that has recently been reported to be present in the endothelial cells that constitute the BBB, and suggest that P-gp may be responsible for this activity. By measuring the BBB transport of the model peptides in the presence of verapamil (a P-gp inhibitor), the intrinsic BBB permeabilities (due to passive diffusion only) were obtained. The presence of verapamil caused a significant increase in the BBB permeabilities of six of the seven model peptides. When the intrinsic permeability coefficients were correlated with several physicochemical parameters, it was shown that hydrogen bonding potential rather than lipophilicity had the greatest influence on the passive diffusion of these model peptides across the BBB. From these studies it can be concluded that inhibition of P-gp, as well as reduction of the hydrogen bonding potential, can be used as strategies to increase peptide transport across the BBB.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
298-303
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
The effect of verapamil on the transport of peptides across the blood-brain barrier in rats: kinetic evidence for an apically polarized efflux mechanism.
pubmed:affiliation
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't