Linked Life Data

8216348

Source:http://linkedlifedata.com/resource/pubmed/id/8216348

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1993-11-1
pubmed:abstractText
The cellular uptake of phosphonylmethoxypropyl cytosine (HPMPC) was characterized to gain insight into the molecular properties that allow this anticytomegalovirus drug to permeate cell membranes. The time course of uptake of HPMPC into Vero cells was linear between 10 and 75 min and proportional to the concentration in the medium from 10(-6) to 10(-2) M. HPMPC uptake was temperature sensitive and the rate of uptake was considerably lower at 27 degrees than at 37 degrees and almost totally inhibited at 4 degrees. In competition studies with naturally occurring nucleosides, nucleotides or the phosphonylmethoxyethyl derivatives, none affected the uptake of HPMPC at concentrations up to 2000-fold molar excess. The uptake of [3H]HPMPC into Vero cells was compared with that of [14C]sucrose, a probe for fluid-phase endocytosis. Kinetics for both compounds were very similar, as were the effects of the microtubule antagonist colchicine and the tumor promoting agent phorbol myristate acetate. Colchicine and the phorbol ester are known to, respectively, inhibit and stimulate endocytosis. It is concluded from these data that HPMPC enters Vero cells by fluid-phase endocytosis and that once internalized it may accumulate in the lysosome. Protonation of the negative charge on the phosphonyl group in HPMPC may allow its diffusion across the lysosome membrane and eventual activation to its putative active diphosphorylated form in the cell cytoplasm.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1053-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Mechanism of uptake of the phosphonate analog (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) in Vero cells.
pubmed:affiliation
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38101-0318.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't