Linked Life Data

19762432

Source:http://linkedlifedata.com/resource/pubmed/id/19762432

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-1-26
pubmed:abstractText
Folic acid is a vitamin essential for thymidylate and purine synthesis. The human proton-coupled folate transporter (hPCFT) has recently been identified as a pH-dependent folic acid transporter, and mutations in this transporter have been linked to hereditary folic acid malabsorption. In this study, we assessed hPCFT-mediated transport activity in vitro, intersubject variability of intestinal expression in relation to blood folates, and the relationship of proton-pump inhibitor (PPI) therapy on hPCFT expression in vivo. We created a Madin-Darby canine kidney strain II (MDCKII) cell line stably expressing hPCFT to evaluate its drug substrates and inhibitors. Intestinal pinch biopsies (duodenum, ileum, colon) were collected from patients undergoing routine endoscopy procedures, and expressed levels of hPCFT were determined by RT-PCR. When assessed using MDCKII-hPCFT cells, folic acid and methotrexate were found to be high-affinity hPCFT substrates. Sulfasalazine and pyrimethamine were noted to inhibit hPCFT activity with Ki values of 42.3 and 161.7 micromol/l, respectively. hPCFT was localized to the brush-border membrane of enterocytes with highest expression in the duodenum and reduced levels in the ileum and colon. When we assessed hPCFT expression in a subset of patients who were receiving PPI therapy, a near 50% reduction in duodenal hPCFT mRNA expression was noted. These results suggest that hPCFT transporter activity can be modulated by many drugs in clinical use, and expression of this transporter in the gastrointestinal tract is higher in the duodenum than more distal sites (duodenum > ileum > colon). Importantly, we note that PPI drug use appears to be associated with reduced hPCFT expression in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1522-1547
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
298
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G248-54
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19762432-Animals, pubmed-meshheading:19762432-Biopsy, pubmed-meshheading:19762432-Cell Line, pubmed-meshheading:19762432-Colon, pubmed-meshheading:19762432-Dogs, pubmed-meshheading:19762432-Duodenum, pubmed-meshheading:19762432-Enterocytes, pubmed-meshheading:19762432-Folic Acid, pubmed-meshheading:19762432-Folic Acid Antagonists, pubmed-meshheading:19762432-Humans, pubmed-meshheading:19762432-Ileum, pubmed-meshheading:19762432-Intestinal Mucosa, pubmed-meshheading:19762432-Kidney, pubmed-meshheading:19762432-Membrane Transport Proteins, pubmed-meshheading:19762432-Methotrexate, pubmed-meshheading:19762432-Proton Pump Inhibitors, pubmed-meshheading:19762432-Proton-Coupled Folate Transporter, pubmed-meshheading:19762432-RNA, Messenger, pubmed-meshheading:19762432-Transfection, pubmed-meshheading:19762432-Tritium
pubmed:year
2010
pubmed:articleTitle
The human proton-coupled folate transporter (hPCFT): modulation of intestinal expression and function by drugs.
pubmed:affiliation
Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London Health Sciences Centre-Univ. Campus, 339 Windermere Rd., London, Ontario, Canada.
pubmed:publicationType
Journal Article