Transport phenomena in the nervous system : physiological and pathological aspects : [proceedings of the satellite symposium of the International Society for Neurochemistry held in Padua, Italy, September 9-11, 1975]

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Transport phenomena in the nervous system : physiological and pathological aspects : [proceedings of the satellite symposium of the International Society for Neurochemistry held in Padua, Italy, September 9-11, 1975]

edited by Giulio Levi, Leontino Battistin, and Abel Lajtha

(Advances in experimental medicine and biology, v. 69)

Plenum Press, c1976

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Description and Table of Contents

Description

This book presents the papers that were delivered at the Satellite Symposium of the International Society for Neurochemistry in Padua, September, 1975. Having such Satellite Symposia was a new experiment for the Society, and all signs, including those from Padua, indicate that it was a very successful experiment, which will be an old tradition for the Society. The large international meeting affords the opportunity for presentations from all areas, for meeting of colleagues from various backgrounds and disciplines. The Satellite Symposia allow people from the same area of interest to discuss their subject in depth, and as such represent meetings of possibly the greatest practical significance for the partici- pants. The Padua Symposium was no exception: all who particiDated in it could testify to its success in exchanging of information, learning of new approaches, and acqu~r~ng of new ideas, also the strengthening of old friendships, forming of new friendships and new collaborations, and exposing ideas to criticisms, suggestions, discussions. As a sign of the interest and success of the partici- pants I can mention that all participants have sent in their contributions. Perhaps editors of volumes would anpreciate that the very last came in no later than two months past the deadline.

Table of Contents

Section I Metabolite Transport.- Metabolite Transport at Cell Membranes.- Mediation of apparently spontaneous metabolite migrations.- Each active transport has a reverse phase.- Meaning of duality or multiplicity of transport systems.- Evidence that exodus occurs by reversal of a weaker pump.- Increased importance of discriminating distinct transport systems.- Roles of receptor sites for amino acid transport in neurotransmission?.- The place of the hydrogen ion.- The future: Generation versus interconversion of energetic gradients.- Possible Role of Glutathione in Transport Processes.- Enzymatic synthesis and degradation of glutathione.- The ?-glutamyl cycle.- Evidence for the function of the ?-glutamyl cycle in amino acid transport.- Heritable disorders of metabolism due to deficiencies in enzymes of the ?-glutamyl cycle.- Section II Barriers in the Living Brain.- Transport Mechanisms in the Cerebrospinal Fluid System for Removal of Acid Metabolites from Developing Brain.- Maturation of bulk flow.- Development of intracranial mechanisms for efflux of:.- (a) para-aminohippuric acid (PAH).- (b) 5-hydroxyindoleacetic acid (5-HIAA).- Sink action of the cerebrospinal fluid (CSF) system.- The Morphological Approach to the Study of Normal and Abnormal Brain Permeability.- Induced opening of the blood-brain barrier.- tumors.- hyperosmotic opening.- hypertensive opening.- Loci where there is no barrier.- permeable vessels.- The Transport of Metabolizable Substances into the Living Brain.- Glucose and other energy yielding substances.- Glucose.- ketone bodies.- pyruvate and lactate.- Amino acids.- differences in influx of amino acids into the brain.- exclusion of amino acids from the brain by inhibition of transport mechanisms.- two sites of cerebral transport.- The relation of cerebral transport to various brain disorders.- aminoacidurias.- changes in transport which affect neurotransmitters.- hormonal abnormalities affecting transport into the brain.- The Specificity of Amino Acid and Sugar Carriers in the Capillaries of the Dog Brain Studied in Vivo by Rapid Indicator Dilution.- Methods and interpretation.- Carrier for amino acids.- Sugar carrier.- Possible Role of Insulin in the Transport of Tyrosine and Tryptophan from Blood to Brain.- Insulin effect on amino acid concentrations.- Mechanism of the effect.- Conclusion.- The Influence of Liver-Bypass on Transport and Compartmentation in vivo.- Consideration of the transformation of metabolizeable.- molecules after they have entered the brain from the blood.- Metabolic labelling patterns from various precursor substrates the evidence for the compartmentation of metabolism within the brain.- Evidence for rapid transformation of transported substrates.- Substrate uptake and metabolism in a pathological condition affecting astrocytes.- comparative studies between normal rats and animals with a portocaval anastomosis.- Certain Aspects of Drug Distribution to Brain.- Transcapillary exchange.- Blood-brain barrier permeability.- Drug distribution to brain.- Penetration of Proteins in the Central Nervous System.- Penetration of proteins into the CSF.- Penetration of proteins into the tissue.- Routes of penetration.- Increased penetration.- Pathological conditions.- Pharmacological studies.- Section III Transport Studies in Various Nervous Tissue Preparations.- The Characteristics of Glucose Transport Across the Blood Brain Barrier and its Relation to Cerebral Glucose Metabolism.- Glucose transport kinetics under physiological conditions.- Glucose transport kinetics during hypoglycemia.- Glucose transport kinetics during anoxia.- Mechanism of glucose transport.- Comparison with glucose transport in the erythrocyte.- Proposed model for glucose transport at the blood brain interface.- Mechanisms for the Passive Regulation of Extracellular K+ in the Central Nervous System: The Implications of Invertebrate Studies.- K+ homeostasis.- The function of astrocytes.- Invertebrate studies.- Vertebrate studies.- glia as spatial buffers for K+.- Crustacean studies.- Amino Acid Transport in Spinal and Sympathetic Ganglia.- Structure and functions of dorsal root and superior cervical ganglia.- The neurone - glia functional unit.- Uptake of putative amino acid transmitters.- effect of dorsal root section.- metabolic requirements.- kinetic characteristics and sodium dependence.- Localization of amino acids.- Drug inhibition of GABA and glutamate uptake.- Amino acid release.- Exchange processes.- Conclusions.- Uptake of Neurotransmitters and Precursors by Clonal Cell Lines of Neural Origin.- Transport in clonal cell lines.- Uptake of ?-aminobutyric acid (GABA).- Uptake of aspartate, glutamate, glycine and taurine.- Transport of choline.- Transport of precursors and biogenic amines.- On the Uptake Mechanism of Choline in Nerve Cell Cultures.- Cell cultures.- Choline uptake experiments.- Results.- Discussion.- The Uptake and Release of ?-Aminobutyric Acid (Gaba) by the Retina.- Role of GABA in the retina.- GABA uptake in the retina.- Effect of GABA-T inhibitors on GABA uptake.- Sites of GABA uptake.- subcellular distribution of (3H)GABA.- autoradiographic localization of GABA uptake sites.- Efflux of GABA from the retina.- Amino Acid Transport in Isolated Neurons and Glia.- Bulk-prepared neuronal and glial cell fractions as models for amino acid transport studies.- General features of amino acid transport in neuronal and glial cells.- High-affinity uptake in relation to transmitter inactivation.- Metabolic and ionic requirements for amino acid uptake.- Amino acid release from isolated fractions as studied by perfusion.- Inhibitors as tools to study cell specificity of amino acid uptake.- Glutamate-glutamine compartmentation.- Summary.- Transport of Taurine in the Central Nervous System.- Taurine transport in vitro.- Taurine influx in vitro.- Taurine efflux in vitro.- Taurine binding to synaptosomal membranes.- Transport of Adenine Derivatives in Tissues of the Brain.- Translocation and central effects of adenosine.- Entry of adenine derivatives to tissues of the brain.- Adenine.- Adenosine.- Hypoxanthine.- adenine mononucleotides.- Output of adenine derivatives from cerebral tissues.- released compounds and cyclic AMP.- Intracellular movements of adenine derivatives.- Kinetical Analysis of the uptake of Glucose Analogs by rat Brain Cortex Slices from Normal and Ischemic Brain.- Uptake of glucose analogues by slices from normal brain.- A model of the brain slice.- determination of model parameters.- uptake of glucose analogues and mannitol.- determination of the cellular transport by model fitting.- extracellular diffusion versus membrane transport.- Uptake of glucose analogues by slices from ischemic brain.- determination of model parameters.- uptake of glucose analogues and mannitol.- comparison between the membrane transport in slices from.- normal and ischemic brain.- Summary and conclusions.- Uptake and Exchange of Gaba and Glutamate in Isolated Nerve Endings.- Synaptosomal exchange of GABA and glutamate.- concentration dependence of exchange.- sodium-dependence of synaptosomal exchange of GABA and glutamate.- substrate specificity of GABA exchange.- parallel decrease of GABA uptake and exchange.- effects of ouabain and of calcium ionophore A.- Concluding remarks.- Mechanisms of Transport for the Uptake and Release of Biogenic Amines in Nerve Endings.- general characteristics of transport.- Mechanisms of transport.- ion-gradient hypothesis for transport, general.- ion gradient hypothesis for the transport of amines.- criticisms of the ion gradient hypothesis, general.- criticisms of the ion gradient hypothesis, amines.- recent developments in amine transport research.- effect of Na+ on the kinetic constants for transport.- Electrolytes and storage and mobilization of amines.- Evidence for outward transport.- various effects of transport inhibitors.- role of transport in synaptic transmission.- Characteristics of the uptake and Release of Glutamic acid in Synaptosomes from rat Cerebral Cortex. Effects of Ouabain.- Preparation of slices and synaptosomes.- Metabolism of glutamic acid.- Uptake and release of glutamic acid.- Effects of ouabain on uptake.- Release of Biogenic Amines from Isolated Nerve Endings.- Superfusion of synaptosomes.- Some aspects of norepinephrine release from superfused synaptosomes.- Effect of d-amphetamine on the release of biogenic amines.- Relationship between structure and releasing activity of.- ss-phenylethylamine derivatives.- effects on norepinephrine.- effects on dopamine.- effects on 5-hydroxytryptamine.- Transport of Dopamine in Discrete Areas of the Striatum and of Cerebral Cortex in the Rat.- Demonstration of the presence of dopaminergic terminals.- in the rat cerebral cortex.- Reuptake process as a tool to estimate and differentiate.- catecholaminergic innervation in brain structures.- general characteristics.- evidence for a specific 3H-DA uptake in the cerebral.- cortex of the rat.- 3H-Dopamine uptake on microdiscs of cerebral tissues.- distribution of dopaminergic terminals in the rat striatum.- distribution of 3H-DA uptake in the cerebral cortex of the rat.- localization of the cell bodies of the cortical dopaminergic.- terminals.- Section IV Factors Influencing Transport.- Energetics of Low Affinity Amino Acid Transport into Brain Slices.- scope.- rationale for studying slices.- Background.- other reviews.- brain slices.- Does active transport of amino acids require glycolysis, phosphorylation and ATP?.- evidence from bacterial studies.- comparison of properties of isolated vesicles, cells and slices.- Experimental dissociation of transport from glycolysis.- How does active transport of amino acids require K+ or Na+.- the K+ requirement is not specific.- the role of Na+ is more difficult to determine: a. changing.- Na+ and K+ simultaneously.- b. Na+ flux relationship to amino acid uptake.- summary of Na+ relationship to uptake.- Dissociation of ion pump activity from uptake.- Potassium Effects on Transport of Amino Acids, Inorganic Ions and Water: Ontogenetic and Quantitative Differences.- Potassium effects on amino acid transport.- Release.- uptake.- Potassium effects on transport of inorganic ions and water.- Potassium effects on metabolism.- energy metabolism.- Na+-K+-ATPase.- Evidence for a Synthesis-Dependent Release of Gaba.- GABA-dependent inhibition.- Studies on the synthesis-dependent release of GABA in vitro.- Functional significance of the release of newly synthesized.- GABA and other neurotransmitters.- Transport of Amino Acids and Catecholamines in Relation to Metabolism and Transmission.- neurotransmitter uptake.- neurotransmitter release.- experimental approach to the study of transmitter flux.- The shuttling of dopamine across the membrane of corpus.- striatum synaptosomes: The differential effect of d- amphetamine.- experimental procedure.- results and conclusions.- The existence of a continuous membrane flux for transmitters.- Changes in Cerebral Amino Acid Transport During Development.- Developmental changes of enzyme patterns.- Extracellular space and ion content.- Amino acid transport.- Section V Relationship of in vivo and in vitro Studies.- The Usefulness of Studies in vitro for Understanding Cerebral Metabolite Transport in vivo.- Barriers in vitro and in vitro.- Rates of cerebral protein synthesis in vitro and in vitro.- Observations on in vitro alterations.- Substrate specificity of transport vivo and in vitro.- Aspects of transport that can be studied better in vitro.- Function of the barriers.- Metabolite compartmentation in vitro and in vitro.- Conclusions.- Release of Amino Acids from the Spinal Cord in vitro and in vivo.- Release of amino acids from spinal cord slices.- Release of amino acids from spinal cord nerve endings.- Release of amino acids from isolated spinal cord.- Release of amino acids from intact spinal cord.- Conclusion.- The Distribution of Drugs in the Central Nervous System.- Drug distribution between blood and CSF.- salicylic acid.- p-aminosalicylic acid.- penicillin.- gentamiein.- Section VI Alterations of Transport in Pathology.- Cerebral Permeability Phenomena in Epilepsy.- Level and uptake in vitro.- Uptake in vitro.- Regional uptake in vitro.- Conclusions.- Pathological Aspects of Brain Transport Phenomena.- The effect of mercury on BBB.- The effect of hyperosmolar perfusate on BBB.- Ischemia.- the effect on BBB.- the effect on synaptosomes.- The effect of oxygen saturation and p CO2 tension on the.- transport from blood to brain.- In vitro studies.- In vitro studies.- Brain Damage and Oral Intake of Certain Amino Acids.- Excitotoxic amino acids.- Cysteine neurotoxicity.- Discussion.- Physiopathology of the Blood-Brain Barrier.- Cerebral oedema and fluid movement across cerebral capillaries.- Volume control of cerebral fluids.- Solute movement and accumulation as volume determinants.- Primary mechanisms of volume control.- Conclusions.- Brain Barrier Pathology in Acute Arterial Hypertension.- Acute hypertension induced by vasoactive substances.- Acute hypertension induced by clamping of the thoracic aorta.- Renal hypertension.- The location of BBB lesions in different species.- The pathophysiology of the permeability disturbance.- the influence of vasoactive substances.- mechanical effects of high intraluminal pressure.- Fluorescence microscopical and ultrastructural studies of the BBB lesions. Location and mechanisms of the vascular damage.- The protective effect of structural adaptation in the resistance.- vessels in essential hypertension.- The relevance of animal studies on acute hypertension to the.- clinical syndrome of hypertensive encephalopathy.- Conclusions.- Author Index.

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