2011 Fiscal Year Final Research Report
In vivo analysis of intestinal drug absorption using adaptor/efflux transporter gene deficient mice
| Project/Area Number |
22790152
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Keywords | トランスポーター / アダプター / 消化管吸収 / タンパク質間相互作用 |
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| Research Abstract |
Transporter adaptor protein PDZK1regulates several influx transporters(PEPT1and OCTN2) in small intestine, and their expression on the apical membrane is diminished in pdzk1gene knockout mice(pdzk1^<-/->). In addition, we have identified that PDZK1regulates the expression of organic anion transporting polypeptide OATP1A and intestinal absorption of its substrate, estrone-3-sulfate. In the present study, we attempted to use pdzk1^<-/-> mice to functionally identify influx transporters responsible for intestinal absorption of cimetidine. Contrary to our expectation, the expression level of intestinal efflux transporter for cimetidine, BCRP, was significantly decreased in pdzk1^<-/-> mice, and plasma concentration of cimetidine after oral administration to pdzk1^<-/-> mice was higher than that in wild-type mice. Taken together, these findings demonstrate that PDZK1plays a pivotal role in the apical localization of both influx transporters and efflux transporter in small intestine.
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[Journal Article] PDZK1regulates organic anion transporting polypeptide Oatp1a in mouse small intesti2010
Author(s)
Sugiura T, Otake T, Shimizu T, Wakayama T, Silver DL, Utsumi R, Nishimura T, Iseki S, Nakamichi N, Kubo Y, Tsuji A, Kato Y
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Journal Title
Drug Metab Pharmacokinet
Volume: 25(5)
Pages: 588-598
DOI
Peer Reviewed
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[Journal Article] Functional expression of carnitine/organic cation transporter OCTN1/SLC22A4 in mouse small intestine and liver2010
Author(s)
Sugiura T, Kato S, Shimizu T, Wakayama T, Nakamichi N, Kubo Y, Iwata D, Suzuki K, Soga T, Asano M, Iseki S, Tamai I, Tsuji A, Kato Y
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Journal Title
Drug Metab Dispos
Volume: 38(10)
Pages: 1665-1672
DOI
Peer Reviewed
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[Journal Article] Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN12010
Author(s)
Kato Y, Kubo Y, Iwata D, Kato S, Sudo T, Sugiura T, Kagaya T, Wakayama T, Hirayama A, Sugimoto M, Sugihara K, Kaneko S, Soga T, Asano M, Tomita M, Matsui T, Wada M, Tsuji A
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Journal Title
Pharm Res
Volume: 27(5)
Pages: 832-840
DOI
Peer Reviewed
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