Table Of ContentProceedings in Life Sciences
E. Petzinger, R. K. H. Kinne, H. Sies
(Eds.)
Hepatic Transport of
Organic Substances
With 118 Figures
Springer-Verlag Berlin Heidelberg NewY ork
London Paris Tokyo
Professor Dr. ERNST PETZINGER
Institut fUr Pharmakologie und Toxikologie
Universitiit Giel3en.·
Frankfurter Stral3e 107
6300 Giel3en/FRG
Professor Dr. ROLF K. H. KINNE
Max-Planck-Institut fUr Systemphysiologie
Rheinlanddamm 201
4600 Dortmund lIFRG
Professor Dr. HELMUT SIES
Institut fUr Physiologische Chemie I
Universitiit Dusseldorf
Moorenstral3e 5
4000 Dusseldorf lIFRG
ISBN -13 :9 78-3-642-74249-1 e-ISBN- 13: 978-3-642-74247-7
DOl: lO.1007/978-3-642-74247-7
Library of Congress Cataloging-in-Publication Data.
Hepatic transport in organic substances 1 E. Petzinger, R. K. H.Kinne, H. Sies (ed.).
p. cm. --(Proceedings in life sciences)
Proceedings of a symposium, held May 8-11, 1988 at Schloss Ringberg, Rottach Egern.
Includes index.
ISBN-13:978-3-642-74249-1 (U.S.: alk. paper)
1. Liver--Physiology--Congresses. 2. Biological transport--Congresses.
3. Biomolecules--Metabolism--Congresses.
4. Organic compounds--Metabolism--Congresses.
I. Petzinger, E. (Ernst), 1950-. II. Kinne, RolfK. H. III. Sies, H. (Helmut), 1942-. IV. Series.
[DNLM: 1. Liver--metabolism--congresses. WI 702 H5296 1988]
QP185.H47 1989 612'.35--dc 19 DNLM/DLC for Library of Congress 88-38907 CIP
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Preface
During recent years, the application of modern techniques has
dramatically increased our insights into the cellular and
molecular mechanisms comprising the chain of events involved
in the transport of organic solutes into, out of, and across
the hepatocyte. A major component facilitating this progress
was the acceptance by the majority of hepatologists that
general principles derived for membrane transport processes in
epithelial cells such as kidney and intestine are also applic
able to the hepatocyte despite its more complex morphology and
the predominance of intracellular modification of organic com
pounds.
The Ringberg Symposium, whose proceedings are compiled in this
volume, was thus aimed to foster this way of consideration
even further by bringing together scientists whose work
focusses on membrane events in general and transport events in
particular. In doing so, this symposium can be considered as a
continuation of the series of books initiated in 1981 by the
publication of "Renal Transport of Organic Solutes" edited by
R. Greger, F. Lang. and S. Silbernagl. followed in 1983 by
"Intestinal Transport: Fundamental and Comparative Aspects"
edited by M. Gilles-Baillieu and R. Gilles.
In planning the symposium, it became evident that time would
not permit to include transport events which occur via vesi
cular uptake and transcytosis, although these transport
processes are involved in a large number of hepatic functions.
The symposium. held from May 8-11. 1988 at SchloB Ringberg.
Rottach Egern. coincided with the death of Dr. Hans Popper.
VI
eminent hepatologist and role model for generations of liver
physiologists, clinicians, and pathologists. The participants
and the organi.zing committee, therefore, decided to dedicate
the symposium and this volume to him. In his letter, withdraw
ing his participation, Dr. Hans Popper expressed his eagerness
to prepare the Summary Statements ,and "by doing so, to learn a
great deal". We hope that this book confers some of this
eagerness and interest onto its readers and makes the reading
a fascinating and rewarding learning experience.
E. Petzinger
R.K.H. Kinne
H. Sies
List of Contributors
Acker, H. 87 Kramer, W. 297, 372
Akerboom, T.P.M. 295 Krell, H. 33
Anathanarayanan, M. 257 Krenning, E.P. 390
Arias, 1.M. 102 Kurz, G. 267, 344
Baumert, T. 131 Lauterbach, F. 388
Berk, P.D. 195 Levy, D. 279
Blitzer, B.L. 233 Locher, M. 303
Boyer, J.L. 58 Lowe, P.J. 21
Bucuvalas, J.C. 257 Mayer, D. 131
Bultmann, T. 295 Meier, P.J. 286, 305
Burckhardt, G. 297, 372 Meijer, D.K.F. 344
Changchit, A. 377 Mo 1, W. 344
Conrady-Lorck, S. 370 MUller, M. 267, 344
Czekay, R.-P. 388 MUllner, S. 301
de Herder, W.W. 403 Petersen, K.-U. 74, 85
Docter, R. 390 Petzinger, E. 87, 327
Durham, S. 377 Potter, B.J. 195
Eelkman-Rooda, S.J. 403 Reichen, J. 45
Enrich, C. 35 Richter, E. 368
Evans, W.H. 35 Ruetz, S. 286
Fasold, H. 301 Rutger, M. 403
Feng, X.-C. 368 Schafer, S.G. 370
Fichtl, B. 370 Schorn, M. 388
Fleischer, B. 240 Schramm, U. 267
Fleischer, S. 240 Schulze, J. 368
Fries, A. 388 Schwenk. M. 303
Frimmer, M. 309 Sheikh. M.1. 190
Ga ut am, A. 5 8 Sies, H. 121, 295
Gebhardt, R. 177 Simion, F.A. 240
Gerok, W. 267 Simon, F.R. 89
Graf, J. 58, 299 Sorrentino, D. 195
Gregus, Z. 141 Stremmel, W. 195, 211
Guhlmann, A. 131 Stump, D. 195
Haussinger, D. 157 Suchy, F.J. 257
Hardison, W.G.M. 21 Teo, S. 377
Hazenberg, M.P. 403 Ullrich, K.J. 405
Heinz, E. 12 Valantinas, J. 305
Hennemann, G. 390 Visser, T.J. 390, 403
Hentschel, J. 87 Vore, M. 377
Hoffmann, A. 301 Wehner, F. 85, 87
Huber, M. 131 Wilson, F.A. 297
J~rgensen, K.E. 190 Winterhager, J.M. 85
Keppler, D. 131 Wolkoff. A.W. 221
Kiang, C.-L. 195 Zhou, S.-L. 195
Kilberg, M.S. 167, 188 Ziegler, K. 301, 317
Kinne, R.K.H. 3, 87 Zimmerli, B. 305
Klaassen, C.D. 141
In Memoriam Hans Popper
We dedicate this volume to the memory of the eminent hepato
logist Hans Popper, M.D. Ph.O., Gustave L. Levy Distinguished
Service Professor, Mount Sinai School of Medicine, New York,
whO died shortly before this meeting to which he was invited
as a Honorary Chairman.
Dr. Popper's intellect inspired and stimulated at least three
generations of hepatologists and by many Dr. Popper is
considered the founding father of hepatology as it is known
today. His broad range of interest was linked to a sustained
desire to transpose advances in modern biology, morphology,
and physiology to medicine and pathobiology. During his whole
scientific carreer he kept reaching out into new disciplines
to learn more about the liver and its diseases. Dr. Popper
played also a crucial role in catalyzing the development of
hepatology on both sides of the Atlantic.
Dr. Popper had a unique fascinating personality and was an
enthusiastic teacher and clinician. His efforts, like his
life, serve as an inspiration to all of us.
Hans Popper 1903 - 1988
Acknowledgements
As in any endeavor a whole array of interfaces is necessary to
complete" the task successfully. In addition to financial
support which was generously provided by the foundations and
agencies mentioned below, moral support, scientific advice,
and logistic support are indispensable. In this respect our
enthusiastic colleagues and our secretarial staff, notably
Daniela Magdefessel and Christine MUller were instrumental.
Without their effective, understanding, and thoughtful
arrangements and the service of the staff of the Ringberg
Castle, the conference would not have attained the ambiance
necessary for the fruitful exchange of ideas in a relaxed and
hospitable atmosphere. D. Magdefessel. Ch. MUller, F. Drager,
and F. Sieland also carried the major burden in preparing
the final version for the publication of the book which
summarizes the papers and abstracts given at this meeting.
Last but not least we would like to thank all the participants
of the conference, notably the speakers, both the presenters
and discussants, who made this meeting a stimulating voyage
into an exciting scientific territory.
We would like to thank the Deutsche Forschungsgemeinschaft,
the Max-Planck-Gese1lschaft. the Pau1-Martini-Stiftung and the
Thyssen-Stiftung for their generous support.
Furthermore we acknowledge the financial assistance by Bayer
AG, Leverkusen, Byk Gulden Lomberg Chemische Fabrik GmbH,
Konstanz and Schering AG, Berlin.
Contents
Part 1 General Aspects of Hepatic Transport
R.K.H. Kinne
Glutamate-sodium Cotransport in the Kidney: An
Example for the Plasticity of Transport Systems 3
E: Heinz
Energetic Coupling in Secondary Active Transport ... 12
W.G.M. Hardison and P.J. Lowe
The Passage of Molecules into Bile: Paracellular
and Transcytotic Pathways ................•......... 21
H. Krell
Increase in Paracellular Permeability as a
Pathophysiological Principle of Drug-induced
Intrahepatic Cholestasis in Rats ................... 33
W.H. Evans and C. Enrich
The Hepatocyte's Plasma Membrane Domains.
Interrelations with the Endocytic Compartment 35
J. Reichen
Hepatic Spaces and Transport in the Perfused Liver. 45
J.L. Boyer. J. Graf. A. Gautam
New Methodologic Approaches for the Study of
Transport in the Liver ..•.......................... 58
K. -U. Petersen
Transport Processes in Mammalian Gallbladder and
Bi le Duct.......................................... 74
K.-U. Petersen, F. Wehner, J.M. Winterhager
Transcellular Butyrate Transport in Gallbladder
Epithelium .....................••...•.............. 85
