Table Of ContentSubcellular Biochemistry 73
Baoxue Yang
Jeff M. Sands Editors
Urea
Transporters
Subcellular Biochemistry
Volume 73
Series editor
Robin Harris, Northumberland, UK
More information about this series at http://www.springer.com/series/6515
Baoxue Yang · Jeff M. Sands
Editors
Urea Transporters
1 3
Editors
Baoxue Yang Jeff M. Sands
Department of Pharmacology Renal Division, Department of Medicine
School of Basic Medical Sciences and Department of Physiology
Peking University Emory University School of Medicine
Beijing Atlanta, GA
China USA
ISSN 0306-0225
ISBN 978-94-017-9342-1 ISBN 978-94-017-9343-8 (eBook)
DOI 10.1007/978-94-017-9343-8
Library of Congress Control Number: 2014949493
Springer Dordrecht Heidelberg New York London
© Springer Science Business Media Dordrecht 2014
+
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part
of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,
recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or
information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar
methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts
in connection with reviews or scholarly analysis or material supplied specifically for the purpose of
being entered and executed on a computer system, for exclusive use by the purchaser of the work.
Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright
Law of the Publisher’s location, in its current version, and permission for use must always be obtained
from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance
Center. Violations are liable to prosecution under the respective Copyright Law.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
While the advice and information in this book are believed to be true and accurate at the date of
publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for
any errors or omissions that may be made. The publisher makes no warranty, express or implied, with
respect to the material contained herein.
Printed on acid-free paper
Springer is part of Springer Science+Business Media (www.springer.com)
Foreword
Urea Transporters edited by B. Yang and J.M. Sands is a compendium of chapters
about urea transport across membranes and the transporters/channels that medi-
ate it. This is the first book on urea transport since a classic book Urea and the
Kidney edited by Bodil-Schmidt Nielsen in 1970. The editors have recruited the
top workers in the field worldwide to provide us with a far-reaching accounting of
the world’s knowledge about urea transport. The book deals with most aspects of
urea transport from urea transporter molecules, illustrating that the SLC14 family
of proteins most likely function as urea channels and not carriers. The chapter on
the use of transgenic knockout mice to study renal urea transporters by Fenton and
Yang is particularly informative, providing the latest information on the relation-
ship between urea transport and the urinary concentrating mechanism. An exciting
chapter on small molecule inhibitors of urea channels by Verkman and colleagues
provides insight into urea channels as pharmacological targets. Since SLC14 iso-
forms UT-A1 and UT-A3 are expressed in the inner medullary collecting duct,
downstream from sites of sodium chloride transport, inhibition of these transport-
ers can be expected to increase water excretion without affecting sodium chloride
balance. Thus, this family of drugs may provide us with new therapeutic agents for
the treatment of water balance disorders.
I expect that this book will be highly useful as a comprehensive reference work
to provide a foundation for future studies of urea transport. We are living in an
era of information glut, and works such as the one provided by Yang and Sands
are invaluable as a means to rapidly assimilate information on a given topic going
back to the earliest studies. The scholarship is exceptional and book is as up-to-
date as it can be in this era of rapidly expanding knowledge. I wish that more
books with this level of focus and scholarship were available.
Mark A. Knepper
v
Contents
1 Overview and Historical Perspective ........................... 1
Baoxue Yang and Jeff M. Sands
2 Urea ..................................................... 7
Hongkai Wang, Jianhua Ran and Tao Jiang
3 Mathematical Modeling of Urea Transport in the Kidney ......... 31
Anita T. Layton
4 Genes and Proteins of Urea Transporters ....................... 45
Jeff M. Sands and Mitsi A. Blount
5 Structure of Urea Transporters ............................... 65
Elena J. Levin and Ming Zhou
6 Expression of Urea Transporters and Their Regulation ........... 79
Janet D. Klein
7 Biochemical Properties of Urea Transporters ................... 109
Guangping Chen
8 Transport Characteristics of Urea Transporter-B ................ 127
Baoxue Yang
9 Urea Transporter Knockout Mice and Their Renal Phenotypes .... 137
Robert A. Fenton and Baoxue Yang
10 Extrarenal Phenotypes of the UT-B Knockout Mouse ............. 153
Baoxue Yang, Xin Li, Lirong Guo, Yan Meng,
Zixun Dong and Xuejian Zhao
vii
viii Contents
11 Small-Molecule Inhibitors of Urea Transporters ................. 165
Alan S. Verkman, Cristina Esteva-Font, Onur Cil,
Marc O. Anderson, Fei Li, Min Li, Tianluo Lei,
Huiwen Ren and Baoxue Yang
12 Clinical Aspects of Urea Transporters .......................... 179
Jianhua Ran, Hongkai Wang and Tinghai Hu
13 Active Urea Transport in Lower Vertebrates and Mammals ....... 193
Lise Bankir
14 Urea Transport Mediated by Aquaporin Water Channel Proteins .... 227
Chunling Li and Weidong Wang
Contributors
Marc O. Anderson Department of Chemistry and Biochemistry, San Francisco
State University, San Francisco, CA, USA
Lise Bankir INSERM UMRS 1138, Centre de Recherche Des Cordeliers, Paris,
France; Université Pierre et Marie Curie, Paris, France
Mitsi A. Blount Renal Division, Department of Medicine and Department of
Physiology, Emory University School of Medicine, Atlanta, GA, USA
Guangping Chen Department of Physiology, and Renal Division Department of
Medicine, Emory University School of Medicine, Atlanta, GA, USA
Onur Cil Departments of Medicine and Physiology, University of California, San
Francisco, CA, USA
Zixun Dong Department of Pharmacology, School of Basic Medical Sciences,
Peking University, Beijing, China
Cristina Esteva-Font Departments of Medicine and Physiology, University of
California, San Francisco, CA, USA
Robert A. Fenton Department of Biomedicine, Interpret Center, Aarhus University,
Aarhus, Aarhus, Denmark
Lirong Guo Department of Pathophysiology, Norman Bethune College of
Medicine of Jilin University, Changchun, China
Tinghai Hu Department of Nephrology, The Second Affiliated Hospital,
Chongqing Medical University, Chongqing, China
Tao Jiang Department of Pharmacology, School of Basic Medical Sciences,
Peking University, Beijing, China
Janet D. Klein Renal Division, Department of Medicine and Department of
Physiology, Emory University School of Medicine, Atlanta, GA, USA
Anita T. Layton Department of Mathematics, Duke University, Durham, NC, USA
ix
x Contributors
Tianluo Lei Department of Pharmacology, School of Basic Medical Sciences,
Peking University, Beijing, China
Elena J. Levin Verna and Marrs McLean Department of Biochemistry and
Molecular Biology, Baylor College of Medicine, Houston, USA
Xin Li Department of Pharmacology, School of Basic Medical Sciences, Peking
University, Beijing, China
Fei Li Department of Pharmacology, School of Basic Medical Sciences, Peking
University, Beijing, China
Min Li Department of Pharmacology, School of Basic Medical Sciences, Peking
University, Beijing, China
Chunling Li Institute of Hypertension and Kidney Research, Zhongshan School of
Medicine, Sun Yat-sen University, Guangzhou, China
Yan Meng Department of Pathophysiology, Norman Bethune College of Medicine
of Jilin University, Changchun, China
Jianhua Ran Department of Anatomy and Neuroscience Center, Basic Medical
College, Chongqing Medical University, Chongqing, China
Huiwen Ren Department of Pharmacology, School of Basic Medical Sciences,
Peking University, Beijing, China
Jeff M. Sands Renal Division, Department of Medicine and Department of
Physiology, Emory University School of Medicine, NE, Atlanta, GA, USA
Alan S. Verkman Departments of Medicine and Physiology, University of
California, San Francisco, CA, USA
Hongkai Wang Department of Anatomy and Neuroscience Center, Basic Medical
College, Chongqing Medical University, Chongqing, China
Weidong Wang Institute of Hypertension and Kidney Research, Zhongshan
School of Medicine, Sun Yat-sen University, Guangzhou, China
Baoxue Yang State Key Laboratory of Natural and Biomimetic Drugs, Key
Laboratory of Molecular Cardiovascular Sciences, Ministry of Education,
Department of Pharmacology, School of Basic Medical Sciences, Peking U niversity,
Beijing, China
Xuejian Zhao Department of Pathophysiology, Norman Bethune College of
Medicine of Jilin University, Changchun, China
Ming Zhou Verna and Marrs McLean Department of Biochemistry and Molecular
Biology, Baylor College of Medicine, Houston, USA
