Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.64 (
MPP
)
1,876
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Ipratropium bromide
(
IPR
) is an anticholinergic used to treat chronic obstructive pulmonary disease (COPD), and is a substrate of organic cation transporters. The present study aimed to assess the contribution of organic cation transporters to tracheobronchial absorption of
IPR
in vivo by directly injecting [(3) H]
IPR
into the tracheal lumen of mice and measuring its accumulation in tracheal tissue. RT-PCR and immunohistochemical analysis showed that Octn1, Octn2, and Oct2 were localized at epithelial cells in the respiratory tract. Electron-microscopic immunohistochemistry indicated that Octn1 and Octn2 were localized at the apical portions of ciliated epithelial cells of trachea. In vitro uptake studies in HEK293 cells expressing these transporters demonstrated that
IPR
is a preferred substrate of Octn2. Inhibition of mouse tracheal accumulation of [(3) H]
IPR
by carnitine was concentration-dependent, reaching a maximum of 42% at 1 mM, whereas inhibition by 0.1 mM
MPP
(+) amounted to 62%. Tracheal accumulation of [(3) H]
IPR
was unchanged when mice were simultaneously injected with Octn1 substrate ergothioneine and organic anion transporter substrate estrone sulfate. These results suggest that Octn2 is involved in membrane permeation of
IPR
in the respiratory tract in vivo. Targeting organic cation transporters may be an effective strategy for delivery of cationic anti-COPD drugs to patients.
...
PMID:In vivo evidence of organic cation transporter-mediated tracheal accumulation of the anticholinergic agent ipratropium in mice. 2368 92
