Linked Life Data

20020740

Source:http://linkedlifedata.com/resource/pubmed/id/20020740

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-2-1
pubmed:abstractText
Ipratropium bromide, an anticholinergic drug used for the treatment of asthma and chronic obstructive pulmonary disease, has low oral bioavailability, but systemic exposure, superior to oral administration, can be achieved by inhalation. Therefore, we investigated the pulmonary absorption mechanism of ipratropium using human bronchial epithelial BEAS-2B cells. [3H]Ipratropium uptake by BEAS-2B cells was temperature-dependent and saturable, with a K(m) value of 78.0 microM, suggesting involvement of carrier-mediated uptake. An RT-PCR study showed that organic cation/carnitine transporters OCTN1 and OCTN2 are expressed in BEAS-2B cells, but organic cation transporters (OCTs) are not. Uptake of [3H]ipratropium by HEK293 cells expressing OCTN1 (HEK293/OCTN1) and OCTN2 (HEK293/OCTN2) was significantly increased, compared with mock-transfected cells, and the estimated K(m) values were 444 microM and 53.0 microM, respectively. Finally, the contributions of OCTN1 and OCTN2 to ipratropium uptake were evaluated by measuring [3H]ipratropium uptake by BEAS-2B cells in which OCTN1 or OCTN2 gene expression had been silenced. Knock-down of OCTN1 or OCTN2 suppressed the uptake of [3H]ipratropium to 78.2% and 14.8% of that by control BEAS-2B cells, respectively. In addition, another anticholinergic, tiotropium, was also taken up by both HEK293/OCTN1 and HEK293/OCTN2 cells. Therefore, ipratropium and tiotropium are taken up primarily by OCTN2, and to a lesser extent by OCTN1, in bronchial epithelial cells. These findings are consistent with the pharmacological activity of the drugs after administration via inhalation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1543-8392
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
187-95
pubmed:meshHeading
pubmed-meshheading:20020740-Absorption, pubmed-meshheading:20020740-Administration, Inhalation, pubmed-meshheading:20020740-Base Sequence, pubmed-meshheading:20020740-Biological Transport, Active, pubmed-meshheading:20020740-Bronchi, pubmed-meshheading:20020740-Cell Line, pubmed-meshheading:20020740-Cholinergic Antagonists, pubmed-meshheading:20020740-DNA Primers, pubmed-meshheading:20020740-Epithelial Cells, pubmed-meshheading:20020740-Humans, pubmed-meshheading:20020740-Ipratropium, pubmed-meshheading:20020740-Kinetics, pubmed-meshheading:20020740-Lung, pubmed-meshheading:20020740-Organic Cation Transport Proteins, pubmed-meshheading:20020740-Pulmonary Disease, Chronic Obstructive, pubmed-meshheading:20020740-RNA, Small Interfering, pubmed-meshheading:20020740-RNA Interference, pubmed-meshheading:20020740-Scopolamine Derivatives
pubmed:year
2010
pubmed:articleTitle
Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption.
pubmed:affiliation
Department of Membrane Transport and Biopharmaceutics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't