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Alcohol abuse and alcoholism are international problems whose costs
economical ly, psychologically and medically have been well
documented. Alcohol is a unique drug in that the effects of
excessive use can have a deleterious effect on most if not all
organs of the body. The brain is one of the organs most affected by
excessive alcohol consumption. Effects on the brain can be seen in
cognitive function, brain structure and neurochemistry. Over the
past few years, there have been significant advances made in
understanding how alcohol affects brain neurochemistry. This book
examines four major areas, i. e. , membrane lipids, receptors and
ion channels, second messengers, and gene expression, where
significant advancements have been made. The book is divided into
four sections based on the four major areas. In each section, data
are examined that cover a range of approaches from in vitro to in
vivo studies. The section on membrane lipids includes recent
developments in how ethanol affects membrane cholesterol domains,
polyunsaturated fatty acids, the cause and consequences of
phosphatidylethanol formation, and the modulation of membrane
protein function by lipid-protein interaction. The second section
comprises chapters on NMDA and 5-HT3 receptors, including new
aspects on alcohol neurotoxicity and the molecular heterogeneity
that may underlie differences in alcohol sensitivity as well as
chapters on GABA-gated chloride flux, and calcium channels.
One of the most active and productive areas of biological science
in the past decade has been the study of the biochemical and
biophysical prop erties of cell membranes. There is little doubt
that membranes are essen tial components of all cellular systems
and that each type of membrane manifests specific and
characteristic cellular functions. In the nervous system, important
events such as neurotransmission, receptor binding, ion transport,
axonal transport, and cell uptake are all known to take place
within the neural cell membrane. Phospholipids, one of the major
components of membranes, not only provide the membrane with its
structural integrity and physical proper ties, but also play an
important role in regulating membrane function. Attention has
recently been focused on the asymmetric localization of these
molecules, the identification of discrete metabolic pools of
phospholipids within the membrane matrix, and their involvement in
sig nal transmission. Although synaptic membranes generally lack an
active mechanism for the de novo biosynthesis of phospholipids, a
number of enzymic routes are present for their interconversions and
for facilitating metabolic turnover. Metabolites generated during
the interconversion reactions may also exert a great influence in
modulating membrane func tions. The phosphogylcerides of neural
membranes are especially enriched in polyunsaturated fatty acids.
However, only very small amounts of these fatty acids are present
in the free form, and they are maintained in dynamic equilibrium
with the membrane phospholipids."
Alcohol abuse throughout the world is associated with serious
social and medical implications. Problems such as intoxication, tol
erance, and development of physical dependence have been well
recognized. The central nervous system and the liver are especially
affected. There is little doubt that alcohol abuse can result in
organ damage, which in turn leads to deleterious health
consequences to the individual. Understanding ethanol action
presents a special and functional diver challenge because of its
molecular simplicity sity. In fact, the ability for alcohol to
disrupt cellular function is at tributed to its cellular injury
without regard to an apparent specific mechanism of action.
Nevertheless, the key to an effective treatment to this problem is
through research into understanding the mechan isms underlying how
ethanol interacts with cells and membranes. This book is the result
of a cooperative effort among scientists from many nations who met
in a symposium in Taipei, Taiwan, ROC, July 1988. The focus of this
book is on experimental ap proaches to better understand the
molecular mechanisms of ethanol on the biological system. These
recent advances in the examination of the alcohol effects on
cellular function are divided into four sec tions. The first
section addresses specific actions of ethanol on the central
nervous system. The second section is directed to the use of cell
cuI tures in ethanol research and the usefulness of cell cultures
in examination of the effects of ethanol in vitro."
Alcohol abuse throughout the world is associated with serious
social and medical implications. Problems such as intoxication, tol
erance, and development of physical dependence have been well
recognized. The central nervous system and the liver are especially
affected. There is little doubt that alcohol abuse can result in
organ damage, which in turn leads to deleterious health
consequences to the individual. Understanding ethanol action
presents a special and functional diver challenge because of its
molecular simplicity sity. In fact, the ability for alcohol to
disrupt cellular function is at tributed to its cellular injury
without regard to an apparent specific mechanism of action.
Nevertheless, the key to an effective treatment to this problem is
through research into understanding the mechan isms underlying how
ethanol interacts with cells and membranes. This book is the result
of a cooperative effort among scientists from many nations who met
in a symposium in Taipei, Taiwan, ROC, July 1988. The focus of this
book is on experimental ap proaches to better understand the
molecular mechanisms of ethanol on the biological system. These
recent advances in the examination of the alcohol effects on
cellular function are divided into four sec tions. The first
section addresses specific actions of ethanol on the central
nervous system. The second section is directed to the use of cell
cuI tures in ethanol research and the usefulness of cell cultures
in examination of the effects of ethanol in vitro."
One of the most active and productive areas of biological science
in the past decade has been the study of the biochemical and
biophysical prop erties of cell membranes. There is little doubt
that membranes are essen tial components of all cellular systems
and that each type of membrane manifests specific and
characteristic cellular functions. In the nervous system, important
events such as neurotransmission, receptor binding, ion transport,
axonal transport, and cell uptake are all known to take place
within the neural cell membrane. Phospholipids, one of the major
components of membranes, not only provide the membrane with its
structural integrity and physical proper ties, but also play an
important role in regulating membrane function. Attention has
recently been focused on the asymmetric localization of these
molecules, the identification of discrete metabolic pools of
phospholipids within the membrane matrix, and their involvement in
sig nal transmission. Although synaptic membranes generally lack an
active mechanism for the de novo biosynthesis of phospholipids, a
number of enzymic routes are present for their interconversions and
for facilitating metabolic turnover. Metabolites generated during
the interconversion reactions may also exert a great influence in
modulating membrane func tions. The phosphogylcerides of neural
membranes are especially enriched in polyunsaturated fatty acids.
However, only very small amounts of these fatty acids are present
in the free form, and they are maintained in dynamic equilibrium
with the membrane phospholipids."
Lipid Structure, Domains, and Proteins: Molecular Mechanisms of
Ethanol and Anesthetic Actions (C.D. Stubbs, E. Rubin). Membrane
Cholesterol and Ethanol (W.G. Wood et al.). The Effects of Ethanol
on Polyunsaturated Fatty Acid Composition (N. Salem, Jr., G. Ward).
Receptors and Ion Channels: Sensitivity of NMDA Receptors to Acute
and in Utero Ethanol Exposure (S.W. Leslie, M.S. Weaver). Molecular
Mechanisms of Alcohol Neurotoxicity (F.T. Crews et al.). Second
Messenger Systems and Kinases: Nucleoside Transport and
EthanolInduced Heterologous Desensitization (A. Gordon et al.).
Ethanol and Phospholipid Dependent Signal Transduction (J.B. Hoek
et al.). Gene Expression: Regulation of Neuronal Gene Transcription
by Ethanol (M.F. Miles et al.). Effect of Acute and Chronic
Administration of Ethanol on cfos Expression in Brain (F. Le et
al.). 19 additional articles. Index.
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