Linked Life Data

7616397

Source:http://linkedlifedata.com/resource/pubmed/id/7616397

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-8-18
pubmed:abstractText
The polyamines putrescine, spermidine and spermine (SPM) are low molecular weight organic cations that play essential intracellular regulatory roles in cell growth and differentiation. Whereas both de novo polyamine synthesis and transmembrane transport regulate cell polyamine contents, exploitation of pathways as pharmacologic targets has been limited by the lack of agents which specifically block polyamine transport. We now report the synthesis and biologic activity of novel polymeric glutaraldehyde conjugates of putrescine, spermidine and SPM which act at the cell membrane to inhibit polyamine uptake in cultured bovine pulmonary artery smooth muscle cells. Each conjugate caused dose-related inhibition of [14C]polyamine transport in pulmonary artery smooth muscle cells with the polymeric SPM conjugate being most effective in inhibiting the uptake of all three polyamines. Polymeric SPM failed to impair uptake of neutral or charged amino acids or to associate with pulmonary artery smooth muscle cells in a temperature-dependent manner. The polymeric SPM conjugate caused substantial decreases in cell polyamine contents which were associated with concentration-dependent cytotoxicity. Spectroscopic analyses of the polymeric SPM conjugate indicated that its molecular weight was 25 +/- 0.5 kDa, which is equivalent to approximately 90 monomeric--HN(CH2)3NH(CH2)4NH(CH2)3NH(CH2)5--units. These findings indicate that reduced polymeric glutaraldehyde conjugates of the polyamines may function as specific inhibitors of polyamine transport and thus provide a basis for examination of polyamine transport as a pharmacologic target in disorders characterized by dysregulated cell growth and differentiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
181-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
A novel polymeric spermine conjugate inhibits polyamine transport in pulmonary artery smooth muscle cells.
pubmed:affiliation
Division of Pharmacology, College of Pharmacy, A.B. Chandler Medical Center, University of Kentucky, Lexington, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.