Catecholamines 1922 -1971 H. BLASCHKO Adrenaline and related substances were discussed in the 1924 edition of Hefl'ter's Handbook by PAUL TRENDELENBURG. On 164 pages he described what was then known not only of adrenaline and its closest relatives but also of the sympathomimetic compounds such as tyramine and ephedrine. When the present Editors of the Handbook entrusted us with the task of editing the present Volume it was decided to restrict it to adrenaline and the other naturally occurring catecholamines. The sympathomimetic amines in general will be discussed only in their relation to the catecholamines. Since TRENDELENBURG completed his review this field has undergone an enormous expansion. There has been a wealth of new findings, and a succession of new ideas. The new theories that have been built into contemporary thought will be fully discussed in the succeeding contributions. But many of the hypotheses that have been put forward since 1924 have long been discarded and yet, they have often led to important observations that we still consider as valid.

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1: Introduction. Catecholamines 19221971.- 2: The Chromaffin System.- I. Introduction.- II. Distribution of Chromaffin Cells in Vertebrates.- 1. Invertebrates.- 2. Vertebrates.- 3. The Carotid Body.- 4. Peripheral Chromaffin Cells.- III. The Functional Anatomy of the Chromaffin Cell.- 1. Structure of Chromaffin Granules.- 2. Cell Organelles.- 3. Formation of Chromaffin Granules.- 4. Adrenalin-Noradrenaline Storage.- 5. Adrenaline versus Noradrenaline Storage.- 6. Discharge of Contents of Chromaffin Granules.- IV. Innervation of Chromaffin Cells.- 1. Adrenal Medulla.- 2. Extra-Adrenal Chromaffin Cells.- References.- 3: Electron Microscopy of Catecholamine-Containing Structures.- I. Introduction.- II. Identifying Catecholamine-Containing Cellular Organelles.- 1. Identification Criteria.- 2. Chemical Basis for the Selective Staining of Catecholamines.- III. Localization of Catecholamines in Nervous Tissues.- 1. Peripheral Sympathetic Nerve Terminals.- a) Small Granular Vesicles.- b) Large Granular Vesicles.- 2. Central Nerve Terminals.- 3. Localizing Catecholamines in Neuronal Cell Bodies and Non-terminal Axons.- IV. Cytology of Catecholamine-Containing Cells.- 1. The Chromaffin Cells.- 2. Chromaffin Neurons.- 3. Carotid Body Chemoreceptors.- 4. Sympathetic Neurons.- 5. Sympathetic Axons and Terminals.- 6. Central Neurons and Terminals.- V. Conclusions.- References.- 4: Catecholamines in the Invertebrates.- I. Introduction.- II. Catecholamines in the Major Invertebrate Phyla.- 1. Protozoa.- 2. Porifera (Sponges).- 3. Coelenterata.- 4. Platyhelminthes (Flatworms).- 5. Nemertinea (Ribbon Worms).- 6. Annelida (Segmented Worms).- 7. Mollusca.- 8. Arthropoda.- 9. Echinodermata.- 10. Hemichordata, Urochordata, Cephalochordata.- III. Summary and Concluding Remarks.-References.- 5: The Distribution of Catecholamines in Vertebrates.- I. Introduction.- II. Methods Used for the Estimation and Identification of Catecholamines in Tissues and Body Fluids.- III. Distribution of Catecholamines in Tissues and Body Fluids.- 1. Catecholamines in Cyclostomata (Hagfishes and Lampreys).- 2. Catecholamines in Euselachii.- 3. Catecholamines in Teleostii (Bony Fishes).- 4. Catecholamines in Amphibia.- 5. Catecholamines in Reptilia.- 6. Catecholamines in Birds.- 7. Catecholamines in Mammals.- a) Nervous System (Brain, Spinal Cord, Pineal Gland, Cerebrospinal Fluid, Peripheral Nerves and Ganglia).- b) Eye.- c) Adrenal Gland (Adrenal Medulla, Dopamine in the Adrenal Gland, N-methyladrenaline.- d) Extramedullary Chromaffin Tissue.- e) Heart.- f) Lung.- g) Kidney.- h) Thyroid Gland.- i) Reproductive Organs (Male Sex Organs, Female Sex Organs).- j) Gastro-intestinal Tract.- k) Liver.- l) Spleen.- m) Salivary Glands.- n) Pancreas.- o) Catecholamines in the Walls of Blood Vessels.- p) Carotid Body.- q) Adipose Tissue.- r) Skeletal Muscle.- s) Skin.- t) Catecholamines in Blood.- u) Catecholamines in Urine.- v) Cells which Can Form Catecholamines.- Annex: Tables 144.- References.- 6: Synthesis, Uptake and Storage of Catecholamines in Adrenergic Nerves. The Effect of Drugs.- A. Introduction.- B. Adrenergic Nerves.- I. Synthesis.- 1. Main Synthetic Pathway.- a) Tyrosine Hydroxylase.- b) DOPA-Decarboxylase.- c) Dopamines ?-hydroxylase.- 2. Other Synthetic Pathways.- 3. Localization of Synthesis. Effect of Precursors.- 4. Synthesis Inhibitors.- a) Tyrosine Hydroxylase Inhibitors.- b) DOPA-Decarboxylase Inhibitors.- ?) Derivatives of Hydrazine and Hydroxylamine.- ?) Decaborane.- c) Dopamine ?-hydroxylase Inhibitors.- ?) Hydroxybenzyloxyamine.- ?)Disulfiram, Tropolone.- d) Reserpine.- 5. Induction and Regulation of Synthesis.- 6. Synthesis Rate and Kinetics.- II. Uptake.- 1. Introduction.- 2. Uptake of Catecholamines in Organs and Tissues.- 3. Uptake in Adrenergic Nerves.- 4. Specific Uptake in Storage Particles.- 5. Bulk Uptake of Catecholamines after Depletion.- 6. Uptake Estimated by Perfusate Deficit Studies.- 7. The Uptake Process.- 8. Uptake of False Transmitters. Multi Amine Storage.- 9. Effect of Drugs on Catecholamine Uptake in Organs, Nerves and Isolated Particles.- a) Sympathomimetic Amines.- b) Adrenergic Blocking Agents.- c) Neuronal and Ganglionic Blockers.- d) Psychotropic Drugs.- ?) Reserpine 209 ?) Cocaine 211 ?) Imipramine, Desipramine, Amitriptyline 212 ?) d-Lysergic Acid Diethylamide.- e) Enzyme and Metabolic Inhibitors.- f) Various Drugs.- III. Storage.- 1. Storage in Subcellular Particles.- 2. Storage Capacity, Noradrenaline Content in Particles.- 3. Stability of Storage Particles.- 4. Free and Particle-bound Noradrenaline in Homogenates of Adrenergic Nerves and in Organs.- 5. Effect of Drugs.- References.- 7: The Synthesis, Uptake and Storage of Catecholamines in the Adrenal Medulla. The Effect of Drugs.- A. Synthesis.- 1. Formation of Adrenaline; N-methylation of Noradrenaline.- 2. Role of Organelles in Synthesis.- 3. Rate of Synthesis in Adrenal Medulla, and Availability of Newly Formed Hormone for Secretion.- 4. Regulation of Catecholamine Synthesis.- 5. Effect of Precursors.- 6. Inhibitors of Synthesis.- 7. Diagrammatic Illustration of Catecholamine Synthesis and Levels of Physiological and Pharmacological Regulation.- B. Uptake.- 1. Uptake at the Cellular Level.- a) Circulating Amines.- b) Reuptake of Catecholamines Secreted.- c) Functional Significance of Uptake ofCirculating Catecholamines into Adrenal Medulla.- d) False Hormones in Adrenal Medulla.- 2. Uptake in Granules.- a) Methods.- b) Exchange versus Net Uptake.- c) Uptake at High Concentrations of Amine.- d) ATP-and Mg++-dependent Uptake.- e) Other Amine Uptake Mechanisms.- f) Role of ATPase.- 3. Inhibitors of Uptake in Chromaffin Amine Storage Vesicles.- a) Inhibition of ATPase.- b) Competition for Inward Transport.- c) Block of Transport Sites.- 4. Diagrammatic Illustration of Catecholamine Uptake, and Levels of Drug Action.- C. Storage.- 1. Origin of Storage Vesicles.- 2. Isolation of Chromaffin Amine Storage Vesicles.- 3. Chemical Composition.- 4. Storage Complex.- a) Stability of Storage Complex at 0°C.- b) Osmotic Lysis.- c) Stability of Storage Complex at Higher Temperature.- d) Differences between Dopamine, Noradrenaline and Adrenaline Storage.- e) Importance of Medium for Stability.- f) Permeability of Vesicle Membrane. Role of ATPase in Amine Transport.- g) Ca++ as Promoter of Release: In vitro Models of Secretion by Exocytosis ?.- h) Cl?-dependent Acceleration of Spontaneous Release Induced by ATP plus Mg++.- i) Homogeneity of Store.- 5. Effect of Drugs.- a) Stabilizers.- b) Promoters of Release.- c) Depleters.- 6. Diagrammatic Representation of Dynamics of Catecholamine Storage.- References.- 8: Metabolic Degradation of Catecholamines. The Relative Importance of Different Pathways under Physiological Conditions and after Administration of Drugs.- I. Introduction.- II. Metabolic Fate.- 1. Deamination by MAO.- 2. O-Methylat…