Decreased biosynthesis of lung surfactant constituent phosphatidylcholine due to inhibition of choline transporter by gefitinib in lung alveolar cells.

Decreased biosynthesis of lung surfactant constituent phosphatidylcholine due to inhibition of choline transporter by gefitinib in lung alveolar cells. Research Abstract Details 

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Decreased biosynthesis of lung surfactant constituent phosphatidylcholine due to inhibition of choline transporter by gefitinib in lung alveolar cells. Abstract Text:

Naoki Ishiguro,Masanobu Oyabu,Toshihiro Sato,Tomoji Maeda,Hironobu Minami,Ikumi Tamai,Naoki Ishiguro,Masanobu Oyabu,Toshihiro Sato,Tomoji Maeda,Hironobu Minami,Ikumi Tamai,

PURPOSE: We investigated whether gefitinib, an anticancer agent, inhibits phosphatidylcholine (PC) biosynthesis and choline uptake by alveolar epithelial type II cells. MATERIALS AND METHODS: Uptake of choline and PC biosynthesis were examined in vitro, using human alveolar epithelia-derived cell line A549 and rat alveolar type (AT) II cells as models. RESULTS: Gefitinib reduced the incorporation of [(3)H]choline into PC in A549 and rat ATII cells. The uptake of [(3)H]choline by A549 and rat ATII cells was concentration-dependent, and the Km values were 15.0 and 10-100 muM, respectively. The uptake of [(3)H]choline by A549 and rat ATII cells was weakly Na(+)-dependent, and inhibited by hemicholinium-3. RT-PCR revealed expression of choline transporter-like protein (CTL)1 and organic cation transporter (OCT)3 mRNAs in both cells. The choline uptake by A549 and rat ATII cells was strongly inhibited by gefitinib with the IC(50) value of 6.77 muM and 10.5 muM, respectively. CONCLUSIONS: Our results demonstrate that gefitinib reduces PC biosynthesis via inhibition of cellular choline uptake by A549 and rat ATII cells, which is mainly mediated by CTL1, resulting in abnormality of lung surfactant that can be one of mechanisms of the interstitial lung disease associated with gefitinib.

Decreased biosynthesis of lung surfactant constituent phosphatidylcholine due to inhibition of choline transporter by gefitinib in lung alveolar cells. Publishing Authors By Initials

N Ishiguro,M Oyabu,T Sato,T Maeda,H Minami,I Tamai,N Ishiguro,M Oyabu,T Sato,T Maeda,H Minami,I Tamai,

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Decreased biosynthesis of lung surfactant constituent phosphatidylcholine due to inhibition of choline transporter by gefitinib in lung alveolar cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Pharmaceutical research

VOLUME: 25

Page Numbers: 417-27

Journal Abbreviation: Pharm. Res.

ISSN: 0724-8741

DAY: 12

MONTH: 07

YEAR: 2007

Decreased biosynthesis of lung surfactant constituent phosphatidylcholine due to inhibition of choline transporter by gefitinib in lung alveolar cells. Information

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LANGUAGE: eng

NlmUniqueID: 8406521

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Grant and Affiliation Information for Decreased biosynthesis of lung surfactant constituent phosphatidylcholine due to inhibition of choline transporter by gefitinib in lung alveolar cells.

AFFILIATION: Department of Membrane Transport and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamasaki, Noda, Chiba, 278-8510, Japan.

Country: United States

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MEDLINETA: Pharm Res

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