Toward a Molecular Basis of Alcohol Use and Abuse

401 Pages·1994·10.57 MB·English

by  Bert L. Vallee (auth.)

EXS71
Toward a Molecular Basis
of Alcohol Use and Abuse
Edited by B. Jansson
H.JomvaIl
U. Rydberg
L. Terenius
B.L. Vallee
Birkhauser Verlag
Basel . Boston . Berlin
Editors
Prof. B. Jansson Prof. H. Jornvall
Department of Psychiatry Department of Medical Biochemistry
Karolinska Institutet and Biophysics
Huddinge University Hospital Karolinska Institutet
S-14186 Huddinge S-171 77 Stockholm
Sweden Sweden
Prof. U. Rydberg Prof. B.L. Vallee
Prof. L. Terenius Center for Biochemical and
Department of Clinical Neuroscience Biophysical Sciences and Medicine
Karolinska Institutet Harvard Medical School
5-171 76 Stockholm Seeley G. Mudd Building
Sweden 250 Longwood Avenue
Boston, MA 02115
USA
Library of Congress Cataloging-in-Publication Data
Deutsche Bibliothek Cataloging-in-Publication Data
Toward a molecular basic of alcohol use and abuse / ed. by
B. Jansson ... - Basel; Boston; Berlin: Birkhauser, 1994
(Experientia: Supplementum ; 71)
ISBN-13: 978-3-0348-7332-1
NE: Jansson, Bengt [Hrsg.]
The publisher and editor can give no guarantee for the information on drug dosage and adminis
tration contained in this publication. The respective user must check its accuracy by consulting
other sources of reference in each individual case.
The use of registered names, trademarks etc. in this publication, even if not identified as such,
does not imply that they are exempt from the relevant protective laws and regulations or free for
general use.
This work is subject to copyright. All rights are reserved, whether the whole or part of the
material is concerned, specifically the rights of translation, reprinting, re-use of illustrations,
recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks.
For any kind of use permission of the copyright owner must be obtained.
© 1994 Birkhauser Verlag, PO Box 133, CH-4010 Basel, Switzerland
Softcover reprint of the hardcover 1st edition 1994
Camera-ready copy prepared by the authors
Printed on acid-free paper produced from chlorine-free pulp
ISBN-13: 978-3-0348-7332-1 e-ISBN-13: 978-3-0348-7330-7
001: 10.1007/978-3-0348-7330-7
987654321
Contents
Preface ............................................... IX
Perspectives
B.L. Vallee
Alcohol in human history 1
Section 1: Neurophannacological aspects
L. Terenius
Reward and its control by dynorphin peptides 9
C. Alling, L. Gustavsson, C. Larsson, C. Lundqvist, D. Rodriguez
and P. Simonsson
Adaptation of signal transduction in brain . . . . . . . . . . . . . . . . . . . . . . . .. 19
R. Roivainen, B. Hundle and R.O. Messing
Protein kinase C and adaptation to ethanol . . . . . . . . . . . . . . . . . . . . . . .. 29
S. Biffo, G. Dechant, H. Okazawa and y'-A. Barde
Molecular control of neuronal survival in the chick embryo . . . . . . . . . . . . .. 39
N. Wilke, M. Sganga, S. Barhite and M.E Miles
Effects of alcohol on gene expression in neural cells .................. 49
P.L. Hoffman and B. Tabakoff
The role of the NMDA receptor in ethanol withdrawal . . . . . . . . . . . . . . . .. 61
S. Nakanishi, M. Masu, Y. Bessho, Y. Nakajima, Y. Hayashi
and R. Shigemoto
Molecular diversity of glutamate receptors and their physiological functions 71
f.-C. Schwartz, f. Diaz, N. Griffon, D. Levesque, M.-P' Martres and P. Sokoloff
Multiple dopamine receptors: The D3 receptor and actions of substances of
abuse. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 81
P.R. Hartig
Molecular pharmacology of serotonin receptors .. . . . . . . . . . . . . . . . . . .. 93
G.E Koob, S. Rassnick, S. Heinrichs and E Weiss
Alcohol, the reward system and dependence ...... . . . . . . . . . . . . . . . .. 103
VI
Section 2: Biological markers and special clinical features
U. Rydberg
Clinical aspects on molecular probes, markers and metabolism 115
J. Knop
Familial alcoholism: Family, twin adoption and high risk studies 121
G.R. Uhl
Association strategies in substance abuse . 133
L. Farde, S. Pauli, J.-E. Litton, C. Halldin, J. Neiman and G. Sedvall
PET-determination of benzodiazepine receptor binding in studies on alcohol-
ism ............................................. 143
M. Linnoila, M. Virkkunen, T. George, M. Eckardt, J.D. Higley, D. Nielsen
and D. Goldman
Serotonin, violent behavior and alcohol ....... . . .. 155
J.M. van Ree, M. Kornet and C. Goosen
Neuropeptides and alcohol addiction in monkeys .................... 165
l. Diamond andA.S. Gordon
The role of adenosine in mediating cellular and molecular responses to ethanol 175
M. Salaspuro
Helicobacter pylori alcohol dehydrogenase. . . . . . . . . . . . . . . . . . . . . . . .. 185
M. lngelman-Sundberg, l. Johansson, l. Persson, M. Oscarson, Y. Hu,
L. Bertilsson, M.-L. Dahl and F. Sjoqvist
Genetic polymorphism of cytochrome P450. Functional consequences and
possible relationship to disease and alcohol toxicity . . . . . . . . . . . . . . . . .. 197
C.A. Naranjo and K.E. Bremner
Serotonin-altering medications and desire, consumption and effects of alcohol
treatment implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 209
Section 3: Enzymatic aspects
H. Jornvall
The alcohol dehydrogenase system ............................. 221
D. W. Nebert
Drug metabolism and signal transduction: Possible role of Ah receptor and
arachidonic acid cascade in protection from ethanol toxicity ............ 231
J. Piatigorsky, M. Kantorow, R. Gopal-Srivastava and S.l. Tomarev
Recruitment of enzymes and stress proteins as lens crystallins . . . . . . . .. 241
M. Ghosh, A. Avezoux, C. Anthony, K. Harlos and C. C. F. Blake
X-ray structure of PQQ-dependent methanol dehydrogenase . . . . . . . . . . . .. 251
VII
K. Wuthrich
NMR, alcohols, protein solvation and protein denaturation 261
H. Eklund, S. Ramaswamy, B. V. Plapp, M. El-Ahmad, O. Danielsson,
J. -0. Haag and H. Jarnvall
Crystallographic investigations of alcohol dehydrogenases . . . . . . . . . . . . . .. 269
C. Duester
Retinoids and the alcohol dehydrogenase gene family ................. 279
D./.N. Sherman, R.J. Ward, A. Yoshida and T.J. Peters
Alcohol and acetaldehyde dehydrogenase gene polymorphism and alcoholism .. 291
J.-O. Haag, M. Estonius and o. Danielsson
Site-directed mutagenesis and enzyme properties of mammalian alcohol de-
hydrogenases correlated with their tissue distribution ................ 301
B. V. Plapp
Control of alcohol metabolism ................................ 311
J. F. Riordan
Angiotensin converting enzyme inhibitors and alcohol abuse . . . . . . . . . . . .. 323
Section 4: Clinical aspects and pharmacological approaches
B. Jansson
Treatment of alcoholism .................................... 333
M.A. Schuckit
Alcohol sensitivity and dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 341
C. P. O'Brien
Treatment of alcoholism as a chronic disorder . . . . . . . . . . . . . . . . . . . . . .. 349
P.A.J. Janssen
Addiction and the potential for therapeutic drug development .. . . . . . . . . .. 361
W.-M. Keung and B.L. Vallee
Therapeutic lessons from traditional Oriental medicine to contemporary Occi-
dental pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 371
R.O. Brady
Potential gene therapy for alcoholism . . . . . . . . . . . . . . . . . . . . . . . . . . .. 383
E. Cordis
Outlook: Prospects for alcoholism treatment ....................... 395
Subject index ........................................... 405
Preface
Since the dawn of Western civilization, ethanol consumption has profoundly affected human
affairs. In the course of history, the consequences of ethanol use and abuse have focused attention
variously on its nutritional, psychological, medical, sociological, toxicological, philosophical,
legal and religious implications. In this century, public attention has been directed progressively
to the chronic medical consequences including morbidity and mortality, and the resultant
economic burdens. There have often been hopes of decisive preventive or therapeutic action.
However, these hopes have been thwarted by the meager knowledge of the biology and
pathology including their underlying mechanisms of chronic ethanol abuse. This frustration has
been intensified by the increasing realization that ethanol abuse now constitutes one of the major
lethal human afflictions but not enough is known about the mechanisms involved. Ethanol related
problems are multifactorial in character and this poses both investigative and intellectual
challenges. Interdisciplinary barriers of language and knowledge have to be removed or
overcome and dialogue established. The best approach, perhaps, is to develop, share and integrate
pertinent information from the fields of molecular and cell biology. Advances in these areas have
been quite remarkable in recent years and yet they still await translation into pharmacological
progress. All the evidence suggests that we are on the verge of uncovering rewarding possiblities.
Such considerations led us to convene a meeting of scientists working at the frontiers of
molecular and clinical sciences pertinent to the ethanol field. With the support of the Nobel
Foundation, a symposium was held at the Nobel-Forum Conference Center of the Karolinska
Institute in Stockholm in the fall of 1993. The participants were asked to emphasize conceptual
features rather than experimental details of their work in order to stimulate future collaboration
spanning conventional boundaries. Four such major sections now define the organization of the
39 chapters of this volume. Section 1 presents neuropharmacological aspects of ethanol
consumption that include receptors, adaptive responses, signal transduction and the resultant
reward systems. Section 2 deals with biological markers as well as with molecular genetics and
clinical features in studies of families, twins, adoptions, and high risk groups. Section 3 cites
x
advances in the knowledge of alcohol metabolism, including the structure, function and
polymorphism of relevant enzymes. The final section, devoted to clinical aspects and
pharmacological approaches, features both generalized aspects of clinical treatments and
inhibitors of unconventional approaches. The influences and interactions of cultural, social and
other environmental factors with those of personality and behavior are not covered explicitly. It is
hoped, nevertheless, that the present description of the actions of ethanol will be of interest to
those concerned with the making of government policy and with the sociological aspects of
ethanol use.
We are grateful to the Nobel Foundation for its support in providing the impetus to discern corre
lations between molecular events and clinical disease states. In our view, these pages provide
both an introduction to current trends and an indication of more intensive studies yet to come on
the molecular basis of the use and abuse of ethanol.
Finally, we gratefully acknowledge the skilful secretarial assistance and preparation of the
manuscripts by Ann-Margreth Gustavsson.
Bengt Jansson, Hans Jornvall, Ulf Rydberg, Lars Terenius and Bert Vallee
Karolinska Institutet and Harvard Medical School
Stockholm and Boston, January 1994
bward aM olecular Basis of Alcohol Use and Abuse
ed. by B. Jansson, H. JiirnvaI, U. Rydag, L Terenius &B . L Vallee
© 1994 BirkMuserYertag Basel/Switzer1and
Alcohol in human history
Bert L. Vallee
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, 250 Longwood Avenue,
Boston, Massachusetts 02115 USA
Keynote: "Man's supposed love affair with alcohol turns out to have been less of a
passionate infatuation than a marriage of convenience and necessity. "
Summary
The role of ethanol in the history of human development is here summarized under seven topics: I. Alcohol: the
substitute for water as the major human beverage; II. Alcohol as a component of the diet and source of calories;
III. Alcohol, concentration by distillation; IV. The Reformation, Temperance and Prohibition; V. Potable non
alcoholic beverages: Boiled water (coffee, tea); VI. Purification and sanitation of water; VII. The present and
future.
I. Alcohol as the substitute for water as the major human beverage
Until the 19th century human beings in Western society considered water unsuitable for
consumption. The very earliest historic societies, whether Egyptian, Babylonian, Hebrew,
Assyrian, Greek or Roman, unanimously rejected water as a beverage. Through the ages water
was known to cause acute and chronic but deadly illnesses and to be poisonous and therefore
was avoided, particularly when brackish. The Old and New Testaments are virtually devoid of
references to water as a common beverage as is the Greek literature, excepting some positive
statements regarding the quality of water from mountain springs (Marcuse, 1899; Glen W.
Bowersock, personal communication). Bacteriological insight identifying waterborne infections
would not occur until the 19th century. Water purification methods were unknown, and in the
West - in contrast to the East - the benefits of boiling water (thereby destroying bacteria and
other parasites) were neither appreciated nor attributed to that process.
For nearly 10,000 years of known Western history, beer and wine, not water, were the major
daily thirst quenchers, consumed by all ages. This simple statement does not make an impact
commensurate with the consequences of this reality. Seafaring nations and explorers, e.g., knew