Perturbation of rat renal tubule transport of the organic cation amantadine in recent onset streptozotocin-induced diabetes and in uninephrectomy

Simple item page
dc.contributor.authorGoralski, KB
dc.contributor.authorStupack, DG
dc.contributor.authorHatch, GM
dc.contributor.authorSitar, DS
dc.date.accessioned2007-10-05T17:27:40Z
dc.date.available2007-10-05T17:27:40Z
dc.date.issued2001-01-31
dc.description.abstractThe effects of early-stage diabetes mellitus and uninephrectomy on the renal tubule transport of amantadine were investigated. Kidney tubules were isolated from streptozotocin-induced diabetic (+/- insulin treatment), uninephrectomized, and control male Sprague-Dawley rats. There were no differences in the K-m of amantadine uptake in renal proximal and distal tubules for the imposed treatments compared with control values. V-max for amantadine uptake in the proximal tubules of diabetic and uninephrectomized rats was higher than the respective control (P < 0.05). V-max for insulin-treated diabetic rats was similar to control values but was lower than that for untreated diabetic rats (P < 0.05). V-max for distal tubule uptake was not altered by any treatment. Structure-activity studies demonstrated that bicarbonate-dependent amantadine uptake was inhibited by glycolate and lactate, but not by propionate or alpha-, beta-, or gamma -hydroxybutyrate. Early stage streptozotocin-induced diabetes mellitus and uninephrectomy induced changes in the kidney that resulted in a similar selective increase in proximal tubule amantadine uptake. These data represent the first description that experimentally induced diabetes mellitus and uninephrectomy modulate the function of the renal tubule organic cation (amantadine) transport system. Both interventions represent potential models in which phenotypic modulation of the renal elimination of organic cationic drugs may be achieved and studied.en
dc.description.urihttps://www.ingentaconnect.com/content/cndscipub/cjpp/2001/00000079/00000001/art00004en_US
dc.format.extent204121 bytes
dc.format.mimetypeapplication/pdf
dc.identifier.citationCanadian Journal of Physiology and Pharmacology, JAN 2001;79(1):18-24.en_US
dc.identifier.doi10.1139/y00-104
dc.identifier.urihttp://hdl.handle.net/1993/2904
dc.language.isoengen_US
dc.rightsNo part of the NRC Research Press electronic journals may be reproduced, stored, or transmitted in any form or by any means, without the written permission of the publisher, except as stated below. Under the Canadian Copyright Act, individuals may download or print single copies of articles for personal research or study. Any person may reproduce short excerpts from articles in the journals for any purpose that respects the moral rights of authors, provided that the source is fully acknowledged. As a courtesy, the consent of authors of such material should be obtained directly from the author. Authorization to reproduce items for other than personal research or study, as stated above, may be obtained via Access © upon payment of the copyright fee of $10.00 per copy. NRC Research Press also extends certain additional rights to authors. The above rights do not extend to copying or reproduction for general distribution, for advertising or promotional purposes, for creating new collective works, or for resale. For such copying or reproduction, arrangements must be made with NRC Research Press.en
dc.rightsopen accessen_US
dc.statusPeer revieweden
dc.subjectamantadineen
dc.subjectorganic cation transporten
dc.subjectrenal tubulesen
dc.subjectdiabetesen
dc.subjectuninephrectomyen
dc.subjectDISTAL TUBULESen
dc.subjectPHARMACOKINETICSen
dc.subjectBICARBONATEen
dc.subjectQUINIDINEen
dc.subjectQUININEen
dc.subjectNEPHROTOXICITYen
dc.subjectHYDROCHLORIDEen
dc.subjectACCUMULATIONen
dc.subjectINHIBITIONen
dc.subjectIDENTIFYen
dc.titlePerturbation of rat renal tubule transport of the organic cation amantadine in recent onset streptozotocin-induced diabetes and in uninephrectomyen
dc.typejournal articleen_US
Files
Collections
University of Manitoba Scholarship (login required)