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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1998-7-2
pubmed:abstractText
The 19F NMR resonances of intra- and extracellular 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU) in suspensions of human erythrocytes are well resolved. This phenomenon allows its transport behavior to be monitored in a 19F NMR time-course experiment. The rate of L-FMAU uptake at 25 degrees in a suspension containing L-FMAU at an initial extracellular concentration of 4 mM was 7.6 +/- 1.0 x 10(-7) pmol cell(-1) sec(-1) (N = 5). Concentration-dependent uptake studies of L-FMAU indicate the existence of both saturable and nonsaturable transport mechanisms, with a Km for the saturable uptake of approximately 1 mM. Although the transport of L-FMAU at 25 degrees was inhibited significantly (54-65%) by nitrobenzylthioinosine (NBTI) and dipyridamole, consistent with the participation of the nucleoside transporter, these inhibitors did not achieve complete blockage of L-FMAU uptake. The participation of the nucleobase transporter in L-FMAU uptake was ruled out by the absence of competition with uracil uptake, and by the lack of inhibition by papaverine. In addition, the NBTI-insensitive uptake of L-FMAU was not affected by pretreatment of the cells with the sulfhydryl reagent, p-chloromercuriphenylsulfonic acid (pCMBS). However, the NBTI- and dipyridamole-insensitive transport of L-FMAU was found to increase upon treatment of the erythrocytes with butanol, an agent that affects membrane fluidity. The partition coefficient of L-FMAU in octanol/phosphate-buffered saline determined by absorption spectrophotometry was 0.31. These data indicate that under the conditions of the studies, L-FMAU uptake by erythrocytes proceeds by both the nucleoside transporter and nonfacilitated membrane diffusion.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1611-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
19F NMR study of the uptake of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil in erythrocytes: evidence of transport by facilitated and nonfacilitated pathways.
pubmed:affiliation
Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.