Transport Phenomena in the Nervous System

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.