QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nagata, Y. Articles by Sugiyama, Y. Search for Related Content PubMed PubMed Citation Articles by Nagata, Y. Articles by Sugiyama, Y.

CARRIER-MEDIATED UPTAKE OF H₂-RECEPTOR ANTAGONISTS BY THE RAT CHOROID PLEXUS: INVOLVEMENT OF RAT ORGANIC ANION TRANSPORTER 3

Graduate School of Pharmaceutical Sciences, the University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan (Y.N., H.K., Y.S.); School of Pharmaceutical Sciences, Kitasato University, Shirokane, Mitano-ku, Tokyo, Japan (S.H.); and Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Shinkawa, Mitaka, Tokyo, Japan (H.E.)

The choroid plexus (CP) acts as a site for the elimination of xenobiotic organic compounds from the cerebrospinal fluid (CSF). The purpose of the present study is to investigate the role of rat organic anion transporter 3 (rOat3; Slc22a8) in the uptake of H₂-receptor antagonists (cimetidine, ranitidine, and famotidine) by the isolated rat CP. Saturable uptake of cimetidine and ranitidine was observed in rOat3-LLC with K_m values of 80 and 120 µM, respectively, whereas famotidine was found to be a poor substrate. The steady-state concentration of the H₂-receptor antagonists in the CSF was significantly increased by simultaneously administered probenecid, although it did not affect their brain and plasma concentrations. Saturable uptake of cimetidine and ranitidine was observed in the isolated rat CP with K_m values of 93 and 170 µM, respectively, whereas 50% of the uptake of famotidine remained at the highest concentration examined (1 mM). The K_i value of ranitidine for the uptake of cimetidine by the isolated CP (50 µM) was similar to its own K_m value, suggesting that they share the same transporter for their uptake. The inhibition potency of organic anions such as benzylpenicillin, estradiol 17ß-glucuronide, p-aminohippurate, and estrone sulfate for the uptake of cimetidine by the isolated rat CP was similar to that for benzylpenicillin, the uptake of which has been hypothesized to be mediated by rOat3, whereas a minimal effect by tetraethylammonium excludes involvement of organic cation transporter(s). These results suggest that rOat3 is the most likely candidate transporter involved in regulating the CSF concentration of H₂-receptor antagonists at the CP.

This article has been cited by other articles:

				V. Reichel, D. S. Miller, and G. Fricker Texas Red transport across rat and dogfish shark (Squalus acanthias) choroid plexus Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1311 - R1319. [Abstract] [Full Text] [PDF]

				H. Tahara, H. Kusuhara, M. Chida, E. Fuse, and Y. Sugiyama Is the Monkey an Appropriate Animal Model to Examine Drug-Drug Interactions Involving Renal Clearance? Effect of Probenecid on the Renal Elimination of H2 Receptor Antagonists J. Pharmacol. Exp. Ther., March 1, 2006; 316(3): 1187 - 1194. [Abstract] [Full Text] [PDF]

				D. L. Bourdet, J. B. Pritchard, and D. R. Thakker Differential Substrate and Inhibitory Activities of Ranitidine and Famotidine toward Human Organic Cation Transporter 1 (hOCT1; SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3) J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1288 - 1297. [Abstract] [Full Text] [PDF]

				H. Tahara, H. Kusuhara, H. Endou, H. Koepsell, T. Imaoka, E. Fuse, and Y. Sugiyama A Species Difference in the Transport Activities of H2 Receptor Antagonists by Rat and Human Renal Organic Anion and Cation Transporters J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 337 - 345. [Abstract] [Full Text] [PDF]

				M. Kuroda, H. Kusuhara, H. Endou, and Y. Sugiyama Rapid Elimination of Cefaclor from the Cerebrospinal Fluid Is Mediated by a Benzylpenicillin-Sensitive Mechanism Distinct from Organic Anion Transporter 3 J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 855 - 861. [Abstract] [Full Text] [PDF]