Cyclic Nucleotides

Section III. Physiology and Pharmacology of Cellular Regulatory Processes.- 16 Regulation of Carbohydrate Metabolism by Cyclic Nucleotides.- Overview.- A. Regulation of Hepatic Glycogenolysis.- I. Glucagon Stimulation of Hepatic Glycogenolysis.- 1. Evidence That Glucagon Exerts Physiological Control on Hepatic Glycogenolysis.- 2. Role of Cyclic AMP in Glucagon Action.- 3. Role of Cyclic AMP-Dependent Protein Kinase.- 4. Role of Phosphorylase b Kinase.- 5. Activation of Phosphorylase.- 6. Possible Role of Phosphoprotein Phosphatase.- 7. Evidence Against a Role for Ca2+ in Glucagon Stimulation of Glycogenolysis.- II. Catecholamine Stimulation of Hepatic Glycogen Breakdown.- 1. Role of Catecholamines and the Sympathetic Nervous System in the Control of Hepatic Glycogenolysis.- 2. The Nature of the Adrenergic Receptors Mediating Catecholamine Effects on the Liver.- 3. Mechanisms Involved in Adrenergic Stimulation of Hepatic Glycogenolysis.- III. Actions of Vasopressin, Angiotensin II and Oxytocin on Hepatic Glycogenolysis.- IV. Insulin Inhibition of Hepatic Glycogenolysis.- 1. Action Against Glucagon.- 2. Action Against Catecholamines.- V. Glucose Modulation of Hormone Effects on Hepatic Glycogenolysis.- VI. Permissive Effects of Glucocorticoids on Hormone Activation of Liver Phosphorylase.- B. Regulation of Hepatic Glycogen Synthesis.- I. Glucose Inhibition of Hepatic Glycogen Synthesis.- II. Catecholamine Inhibition of Hepatic Glycogen Synthesis.- III. Insulin, Glucose, and Glucocorticoid Stimulation of Hepatic Glycogen Synthesis.- C. Regulation of Hepatic Gluconeogenesis.- I. Glucagon Stimulation of Hepatic Gluconeogenesis.- 1. Evidence That Glucagon Exerts Physiological Control on Gluconeogenesis.- 2. Glucagon Inhibition of Hepatic Pyruvate Kinase.- 3. Glucagon Stimulation of Hepatic Pyruvate Carboxylation.- 4. Apparent Non-Involvement of Pyruvate Dehydrogenase in Glucagon Stimulation of Hepatic Gluconeogenesis.- 5. Glucagon Inhibition of Hepatic P-Fructokinase.- 6. Glucagon Induction of P-Enolpyruvate Carboxykinase.- 7. Other Mechanisms Possibly Involved in Glucagon Stimulation of Gluconeogenesis.- II. Catecholamine Stimulation of Hepatic Gluconeogenesis.- III. Insulin Inhibition of Hepatic Gluconeogenesis.- IV. Permissive Effects of Glucocorticoids on Hormone Activation of Hepatic Gluconeogenesis.- D. Regulation of Muscle Glycogenosis.- I. Catecholamine Stimulation of Muscle Glycogenosis.- 1. Physiological Aspects.- 2. Roles of Cyclic AMP, Cyclic AMP-Dependent Protein Kinase, and Phosphorylase b Kinase.- 3. Activation of Phosphorylase.- 4. Possible Role of Phosphorylase Phosphatase.- 5. Permissive Effects of Glucocorticoids on Catecholamine Stimulation of Muscle Glycogenosis.- E. Regulation of Muscle Glycogen Synthesis.- I. Regulation of Glycogen Synthase by Phosphorylation.- II. Catecholamine Inhibition of Muscle Glycogen Synthesis.- III. Insulin Stimulation of Muscle Glycogen Synthesis.- F. Regulation of Pyruvate Metabolism in Muscle.- G. Regulation of Carbohydrate Metabolism in Adipose Tissue.- I. Catecholamine Effects on Glycogen and Pyruvate Metabolism in Adipose Tissue.- II. Insulin Effects on Glycogen Metabolism in Adipose Tissue.- III. Insulin Effects on Pyruvate Metabolism in Adipose Tissue.- References.- 17 Regulation of Lipid Metabolism by Cyclic Nucleotides.- Overview.- A. Cyclic Nucleotides in Regulation of Triglyceride Breakdown in Adipocytes.- I. Role of Lipid Mobilization from Adipocytes.- II. Adenylate Cyclase Regulation.- 1. Short-Acting Hormones Which Active Adenylate Cyclase Through Receptor Binding: Catecholamines.- 2. Regulation of the Coupling of Hormone-Receptor Complexes to Adenylate Cyclase: Thyroid Hormones.- 3. Adenylate Cyclase Regulation by Inhibition of Deactivation: Cholera Toxin.- 4. Regulation Through Synthesis of Components of Adenylate Cyclase: Growth Hormone and Glucocorticoids.- 5. Inhibition of Adenylate Cyclase.- III. Cyclic AMP Phosphodiesterase Regulation.- IV. Protein Kinase Regulation by Cyclic AMP.- V. Activation of Triacylglycerol Lipase by Protein Kinase.- VI. Lipoprotein Lipase Regulation.- VII. Role of Cyclic AMP Independent Processes in Triglyceride Breakdown.- 1. Calcium and Catecholamine Activation of Lipolysis.- 2. Calcium, Phospholipase A2 Activation, and the Lipolytic Action of ACTH.- 3. Regulation of Lipolysis via Substrate Availability.- B. Catecholamine Activation of Thermogenesis in Brown Adipose Tissue via Cyclic Nucleotides.- I. Role of the Na+/K+ Plasma Membrane Pump in Thermogenic Action of Catecholamines.- II. Mitochondrial Uncoupling by Fatty Acids in the Regulation of Thermogenesis.- III. Cyclic AMP as the Mediator of Catecholamine-Activated Lipolysis.- C. Calcium, Cyclic Nucleotides, and Glycogen Synthase Regulation.- I. Calcium-Dependent Regulation of Glycogen Metabolism by Alpha1-Catecholamines.- II. Relationship Between Alpha1-Adrenergic Stimulation of Phos-phatidylinositol Turnover and Ca2+.- D. Mode of Insulin Action Through Cyclic Nucleotides, Ca2+ and Special Mediators.- I. Insulin Action on Adipocytes. Regulation of Glycogen Synthase and Pyruvate Dehydrogenase.- II. Insulin, Cyclic GMP, and Calcium.- III. Insulin and Hexose Transport.- IV. Menadione, Insulin, and H2O2.- V. Insulin, Catecholamines, and Protein Phosphorylation.- E. Conclusion.- References.- 18 Regulation of the Cell Cycle and Cellular Proliferation by Cyclic Nucleotides.- Overview.- A. Role of Cyclic Nucleotides in Cell Proliferation.- I. Cultured Fibroblasts.- 1. The G+-G0 Interconversion.- 2. Other Cell Cycle Effects of cAMP in Fibroblasts.- II. Liver Cells.- 1. Liver Regeneration.- 2. Continuous Cultures of Liver Cells.- III. Neuroblastoma Cells.- IV. Adrenal Cortical Cells.- V. Thyroid Cells.- VI. Melanoma Cells.- VII. Schwann Cells.- VIII. S49 Lymphoma Cells.- IX. Thymic Lymphocytes.- X. Hemopoietic Stem Cells (CFU-S).- XI. HeLa Cells.- XII. Miscellaneous Cell Types.- XIII. Generalizations on the Actions of Cyclic Nucleotides in Cell Proliferation.- 1. Cell Cycle Loci of cAMP Action.- 2. Speculations on the Physiological Role of cAMP in Growth Regulation.- B. Cyclic Nucleotides and Cancer.- I. cAMP and Properties of Transformed Fibroblasts.- II. Cyclic Nucleotides and Tumors of Liver.- III. Cyclic Nucleotide Levels in Tumors.- IV. cAMP-Dependent Protein Kinase in Cancer Cells.- V. Effects of Elevated cAMP Upon Tumor Growth.- C. Concluding Remarks.- References.- 19 Regulation of Development by Cyclic Nucleotides and Inorganic Ions.- Overview.- A. Introduction.- B. Evidence for the Involvement of Chemical Messengers in Development.- I. Maturation of the Oocyte.- 1. Cellular Events.- 2. Extracellular Messenger.- 3. Involvement of Cyclic Nucleotides.- 4. Involvement of Inorganic Ions.- 5. Maturation of Oocytes From Starfish and Mammals.- 6. Summary.- II. Formation of Cartilage and Muscle in the Limb.- 1. Developmental Events.- 2. Chondrogenesis.- 3. Myogenesis.- 4. Transformation by Sarcoma Viruses.- 5. Summary.- III. Pattern Formation in Dictyostelium Discoideum.- 1. Developmental Events.- 2. Involvement of Cyclic Nucleotides and Inorganic Ions.- 3. Cyclic AMP-Associated Proteins in Multicellular Stages.- 4. Cyclic AMP and Cell Contact.- 5. Cell Contact Effects in Development.- 6. Summary.- C. Chemical Messengers and Gene Expression in Development.- D. Conclusion.- References.- 20 Regulation of Cell Secretion: The Integrated Action of Cyclic AMP and Calcium.- Overview.- A. Introduction.- B. The Calcium Signalling System.- I. General Features.- II. Voltage-Dependent Calcium Channels.- III. Agonist-Dependent Calcium Channels.- IV. Mobilization of Internal Calcium.- V. The Role of Calcium in Stimulus-Secretion Coupling.- VI. Spatial and Temporal Aspects of Calcium Signalling.- VII. A Description of the Drugs Which are Used to Alter Calcium Metabolism.- C. The Integrated Action of Cyclic AMP and Calcium in the Control of Enzyme and Fluid Secretion.- I. Insulin-Secreting ?-Cells.- II. Anterior Pituitary Gland.- III. Mast Cells.- IV. Exocrine Pancreas.- V. Intestine.- VI. Parietal Cells.- VII. Mammalian Salivary Gland.- VIII. Insect Salivary Gland.- D. Conclusion.- References.- 21 Regulation of Water and Electrolyte Movement in Kidney by Vasopressin and Cyclic Nucleotides.- Overview.- A. Vasopressin Action in Kidney and Toad Bladder.- B. Cell Culture Models.- I. MDCK Cell Line.- II. LLC-PK1 Cells.- III. Primary Culture of Toad Bladder Epithelial Cells.- IV. Primary Culture of Glomerular Mesangial Cells.- C. Role of Cyclic AMP in ADH Action — Cellular Mechanisms.- I. ADH Receptors and Adenylyl Cyclase.- 1. ADH Receptor Occupancy and Coupling to Adenylyl Cyclase..- 2. Effects of NaCl.- 3. Effects of Glucocorticoid Hormones.- 4. Interactions with Prostaglandins.- II. Activation of Protein Kinase and Protein Phosphorylation.- III. Protein Dephosphorylation.- 1. Relationship of SCARP to Type II cAMP-PK.- 2. Effects of Steroids on SCARP: A Hypothesis.- IV. ADH Action and Calcium.- 1. Effect of Ca++ on Sodium Transport in Toad Bladder.- 2. Effect of Ca++ on Water Flow in Toad Bladder.- 3. Conclusions.- V. Role of Microtubules and Microfilaments in ADH Action.- 1. Physiological Studies.- 2. Control of Microfilament and Microtubule Organization — A Working Hypothesis for ADH Action.- D. Conclusions.- References.- 22 Regulation of Cellular Excitability by Cyclic Nucleotides.- Overview.- A. Introduction.- B. Measures of Excitability.- I. Transmembrane Properties Using Intracellular Recording.- II. Summed Potentials of Cell Populations.- III. Extracellular Action Potentials of Single Units.- C. Problems of Drug Administration.- I. Perfusion and Superfusion.- II. Microiontophoresis.- III. Micropressure Application.- D. Effect of Cyclic Nucleotides and Related First Messengers on Excitable Cells.- I. Liver.- II. Fat Cells.- III. Glandular Tissue.- 1. Invertebrate Salivary Glands.- 2. Parotid Acinar Cells.- 3. Pineal Gland.- IV. Epithelial Electrolyte Transporting Tissue.- V. Muscle.- 1. Skeletal Muscle.- 2. Cardiac Muscle.- 3. Smooth Muscle.- VI. Photoreceptors.- VII. Invertebrate Neurons.- VIII. Vertebrate Nervous Tissue.- 1. Peripheral Nervous System.- 2. Central Nervous System.- 3. Glia.- E. Conclusions and Speculations.- References.- 23 Regulation of Cardiac Contractile Activity by Cyclic Nucleotides.- Overview.- A. Introduction.- B. Effector Role of Ca2+.- C. Regulatory Effects of Cyclic AMP on Ca2+ Fluxes in the Heart..- I. Calcium Fluxes Across the Sarcolemma.- II. Calcium Fluxes Across the Sarcoplasmic Reticulum.- III. Phosphorylation of the Cardiac Sarcoplasmic Reticulum by Cyclic AMP-Dependent Protein Kinases and Catecholamine-Induced Acceleration of Cardiac Relaxation.- IV. Phosphorylation of the Cardiac Sarcoplasmic Reticulum and the Catecholamine-Induced Increases in Tension Development and Rate of Tension Rise in the Heart.- V. Calcium Fluxes Between the Cytosol and Troponin: Phosphorylation of the Troponin Complex.- VI. Significance of Phosphorylation of Cardiac Phospholamban and.- Troponin.- D. Regulatory Effect of Ca2+ on Cyclic AMP Levels.- References.- 24 Cyclic Nucleotides as First Messengers.- Overview.- A. Intercellular Communication by cAMP Signals.- I. Cyclic Nucleotides and the Cellular Slime Molds.- II. cAMP Signals Elicit a Chemotactic Response, Can be Relayed and are Involved in Cell Development.- B. Biochemical Aspects of the cAMP Signal Generating System.- I. Introduction.- II. Cell Surface Receptors for cAMP.- III. Synthesis and Secretion of Camp.- IV. Destruction of the cAMP Signal.- C. Transduction of cAMP Signals in the Cell.- I. Introduction.- II. Cyclic Nucleotides as Possible Second Messengers.- III. Ca++ Ions as a Second Messenger.- D. Extracellular cAMP Controlled Developmental Changes.- I. Changes During Cell Aggregation.- II. Differentiation into Spore and Stalk Cells.- E. Are There Other Systems That Use cAMP as a Primary Messenger?.- References.- Section IV. Physiology and Pharmacology of Organ Systems.- 25 The Role of Cyclic Nucleotides in the Nervous System.- Overview.- A. Introduction.- I. Cyclic Nucleotides as Second Messengers.- II. Criteria for Evaluating Cyclic Nucleotide Mediation of Physiological Responses.- B. Cyclic AMP.- I. The Role of Cyclic AMP as a Postsynaptic Second Messenger.- 1. Is Cyclic AMP the Second Messenger for NE in the Cerebellum?.- 2. Does Cyclic AMP Mediate the Central Effects of Adenosine and Adenine Nucleotides?.- II. Cyclic AMP as a Modulator of Synaptic Responses.- 1. Cyclic AMP as a Postsynaptic Modulator.- 2. Cyclic AMP as a Presynaptic Modulator.- III. Cyclic AMP and Intermediary Metabolism.- 1. Increases in Cyclic AMP and Metabolic Changes.- 2. Stratial ?-Receptors.- 3. Electrophysiological Experiments.- C. Physiological Role of Cyclic GMP.- I. Acetylcholine and Cyclic GMP.- II. Excitatory Amino Acids and Cyclic GMP.- III. Transmitter Release.- IV. Electrophysiological Effects of Cyclic GMP.- D. Cyclic Nucleotides and Disease States.- I. Manic-Depressive Illness and Lithium Actions.- 1. Acute Effects.- 2. Chronic Effects.- II. Regulation of Neuronal Excitability and Seizure Disorders.- 1. Effects of Seizures on Cyclic Nucleotide Levels in Brain.- 2. Effects of Drugs Which Modify Seizures.- 3. Effects of Cyclic Nucleotide Applications on Neuronal Excitability.- E. Conclusion.- References.- 26 The Role of Cyclic Nucleotide Metabolism in the Eye.- Overview.- A. Introduction.- B. Cyclic Nucleotide Metabolism in the Retina.- I. Cyclic Nucleotides in Rod-Dominant Retinas.- 1. Cyclic GMP.- 2. Cyclic AMP.- II. Cyclic Nucleotides in Cone-Dominant Retinas.- 1. Cyclic AMP and Cyclic GMP Content.- 2. Modulation of Cyclic AMP Levels by Light.- 3. Effect of Freezing.- 4. Effect of Hibernation.- 5. Effect of Iodoacetic Acid-Induced Degeneration of Cone Visual Cells.- III. Cyclic Nucleotides in Retinal Pigment Epithelium.- IV. Abnormalities in Cyclic Nucleotide Metabolism and Retinal Degenerations.- 1. rd (Retinal Degeneration) Mouse.- 2. Irish Setter Dog.- 3. Drug-Induced Photoreceptor Cell Degeneration in Normal Eyes..- 4. Retinal Degeneration in Several Strains of Rats.- C. Cyclic Nucleotide Metabolism in Ocular Tissues Other Than Retina.- I. Ciliary Body-Iris-Aqueous Humor.- II. The Aqueous Outflow System.- III. Lens.- IV. Cornea.- D. Concluding Remarks.- References.- 27 The Role of Cyclic Nucleotides in the Control of Anterior Pituitary Gland Activity.- Overview.- A. Role of Cyclic AMP in the Action of LHRH, TRH, CRF, Somatostatin, Dopamine and “Inhibin” in the Adenohypophysis.- I. Indirect Evidence for a Role of Cyclic AMP in Adenohypo-physeal Function.- II. Stimulatory Effect of LHRH on Cyclic AMP Accumulation.- III. Stimulatory Effect of TRH on Cyclic AMP Accumulation.- IV. Stimulatory Effect of CRF on Cyclic AMP Accumulation.- V. Inhibitory Effect of Somatostatin on Cyclic AMP Accumulation..- VI. Inhibitory Effect of Dopamine on Cyclic AMP Accumulation..- VII. Inhibitory Effect of “Inhibin” on Cyclic AMP Accumulation.- B. Role of Prostaglandins in the Adenohypophysis.- I. Prostaglandins and Adenohypophyseal Cyclic AMP.- II. Fatty Acids and Changes of Adenohypophyseal Cyclic AMP Accumulation in vitro.- III. Prostaglandins and Adenohypophyseal Hormone Release.- 1. PGs and Growth Hormone Release.- 2. PGs and Gonadotropin Release.- 3. PGs and TSH and PRL Release.- 4. PGs and ACTH Release.- C. Role of Ca2+ in the Adenohypophysis.- D. Adenohypophyseal Cyclic AMP-Dependent Protein Kinase and Its Substrates.- E. Pituitary LHRH Receptor.- F. Interactions Between LHRH, Sex Steroids and “Inhibin” in the Control of LH and FSH Secretion.- G. Interactions Between Sex Steroids and Dopamine in the Control of Prolactin Secretion.- H. Alpha-Adrenergic Control of ACTH and Beta-Endorphin Secretion.- References.- 28 The Role of Cyclic Nucleotides in the Thyroid Gland.- Overview.- A. Mechanism of Action of TSH.- I. The TSH Receptor.- 1. Binding of TSH to Thyroid Plasma Membranes.- 2. Characterization of the Receptor.- 3. Coupling Process.- II. TSH and Adenylate Cyclase Activity.- 1. Correlation Between Binding of TSH and Activation of Adenylate Cyclase.- 2. Time Course and Dose Response.- 3. Regulation.- III. TSH and Cyclic AMP Formation.- 1. Cyclic AMP as the Intracellular Mediator of the Effects of TSH..- 2. Time Course and Dose Response.- 3. Regulation.- IV. TSH and Protein Kinase Activity.- 1. Time Course and Dose Response.- 2. Correlation with Cyclic AMP Levels.- 3. Phosphoprotein Phosphatase.- 4. Possible Substrates to be Phosphorylated.- V. Role of Cyclic AMP in Thyroid Metabolism.- 1. Colloid Endocytosis and Exocytosis.- 2. Iodine Metabolism.- 3. Glucose Oxidation.- 4. Nucleic Acid Metabolism.- 5. Protein Synthesis and Growth.- 6. Phospholipid Metabolism.- VI. Inhibitors of TSH-Stimulated Thyroidal Cyclic AMP Formation..- 1. Iodide.- 2. Thyroid Hormones.- 3. Adrenergic Agonists.- 4. Cholinergic Agonists.- B. Other Stimulators of Thyroidal Cyclic AMP Formation.- I. Thyroid-Stimulating Immunoglobulins.- II. Prostaglandins.- III. Adrenergic Agonists.- IV. Cholera Toxin.- C. Desensitization — Characterization of the Phenomenon.- I. Effects on Binding Process.- II. Effect on Cyclic AMP-Adenylate Cyclase System.- III. Effect on Other Metabolic Parameters.- D. Clinical Aspects.- I. Graves’ Disease.- II. Thyroid Nodules.- 1. Functioning Nodules.- 2. Non-Functioning Nodules.- III. Thyroid Carcinoma.- References.- 29 Parathyroid Hormone, Bone and Cyclic AMP.- Overview.- A. Introduction.- B. Cyclic AMP as Messenger in Bone.- C. Heterogeneity of Circulating PTH.- D. Correlations Between Responses to PTH and Changes in cAMP..- I. Hypercalcemic Effect of PTH in vivo.- II. Demineralization Effect of PTH in vitro.- III. Metabolic Effects of PTH in Bone.- 1. Glucose Metabolism.- 2. Lactate Production.- 3. Citrate Production.- 4. Hyaluronate Synthesis.- 5. Collagen Synthesis.- 6. RNA Synthesis.- E. Calcium as Messenger.- References.- 30 The Role of Cyclic Nucleotides and Calcium in Adrenocortical Function.- Overview.- A. Primary Interaction of Effectors with Adrenocortical Cells.- I. ACTH Receptors.- II. Angiotensin Receptors.- B. Adrenocortical Adenylate Cyclase.- I. Adrenocorticotropin.- II. Angiotensin.- III. Cholera Toxin.- IV. Adenosine.- C. Intracellular Cyclic Nucleotides and Calcium Ion.- I. Adrenocorticotropin.- II. Angiotensin.- III. Potassium.- IV. Serotonin.- D. Actions of Cyclic Nucleotides in the Adrenal Cortex.- E. Concluding Remarks.- References.- 31 A Role of Cyclic AMP in the Gastrointestinal Tract: Receptor Control of Hydrogen Ion Secretion by Mammalian Gastric Mucosa.- Overview.- A. Introduction.- B. The Regulation and Pharmacology of Acid Secretion.- C. In vivo, in situ, and in vitro Gastric Studies of Cyclic AMP Metabolism.- I. Exogenous Administration and Intact Mucosa.- II. Cell Free Systems.- III. Isolated Gastric Glands.- D. Isolated Gastric Parietal Cells.- I. Cell Preparations.- II. Parietal Cell Responses and Cyclic Nucleotide Metabolism.- 1. Cyclic Nucleotide Phosphodiesterase Inhibitors.- 2. Adenylyl Cyclase.- E. Recapitulation and Speculation.- I. Second Messengers for Acetylcholine and Gastrin: Relationship to Cyclic Nucleotides and Histamine.- References.- 32 The Role of Cyclic Nucleotides in the Vasculature.- Overview.- A. Introduction.- B. The Role of Cyclic Nucleotides in Vascular Smooth Muscle Contractility.- C. Adrenergic Receptor Modulation of Vascular Cyclic Nucleotides.- D. Cyclic Nucleotides and the Vascular Endothelium.- E. Cyclic Nucleotides and Vascular Disease.- F. The Effect of Cyclic AMP on Calcium Ion Movements in Vascular Muscle Cells.- G. Conclusion.- References.- 33 The Role of Cyclic Nucleotides in the Pineal Gland.- Overview.- A. Introduction.- I. Synthesis of Melatonin.- II. Orcadian Rhythms in Pineal Indoleamines.- III. Neuroendocrine Transduction.- B. Induction of Serotonin N-Acetyl transferase (SNAT) Activity by Beta-Adrenergic Stimulation.- I. Roles of Cyclic AMP.- II. Regulation of Sensitivity to Stimulation.- 1. Accumulation of Cyclic AMP.- 2. Cyclic AMP-Dependent Protein Kinase.- C. Cyclic GMP.- References.- 34 The Role of Cyclic Nucleotides in Epithelium.- Overview.- A. Introduction.- B. Metabolism of Cyclic Nucleotides in Normal Skin.- I. Adenylate Cyclase and Associated Receptors.- 1. Beta-Adrenergic Receptor.- 2. Histamine Receptor.- 3. Adenosine Receptor.- 4. Prostaglandin E2 Receptor.- II. Guanylate Cyclase.- III. Cyclic Nucleotide Phosphodiesterases.- C. Effects of Cyclic Nucleotides on Cells in Culture.- I. Growth of Primary Epidermal Cultures on Plastic.- 1. Adult Guinea Pig Ear.- 2. Neonatal Mouse.- II. Growth of Primary Epidermal Cultures on Collagen Gels.- III. Growth of Primary Epidermal Cultures on 3T3 Feeder Layers..- IV. Outgrowths of Epidermal Cells from Explants.- D. Cyclic Nucleotide Metabolism in Diseased Skin.- I. Cyclic Nucleotide Levels in Psoriasis.- II. Data Supporting an Altered Cyclic Nucleotide System in Psoriasis..- III. Cyclic Nucleotide System in Atopic Dermatitis.- References.- 35 The Role of Cyclic Nucleotides in Platelets.- Overview.- A. Introduction.- I. Natural History of Platelets.- II. Aggregation and Secretion.- III. Changes During Activation.- IV. Effects on Coagulation.- V. Clot Retraction.- B. Adenylate Cyclase.- I. Introduction.- II. Prostaglandins.- 1. Effects on Aggregation and on Cyclic AMP.- 2. Receptors for Prostaglandins.- 3. Physiological Significance.- III. Adenosine.- 1. Inhibition of Aggregation and Stimulation of Adenylate Cyclase.- 2. Inhibition of Adenylate Cyclase.- 3. Receptors for Adenosine.- IV. Catecholamines.- 1. Effects on Platelet Aggregation.- 2. Effects on Cyclic AMP.- 3. Catecholamine Receptors.- V. ADP.- 1. Aggregation and Cyclic AMP Effects.- 2. Inhibition of Adenylate Cyclase.- 3. Platelet Receptors for ADP.- VI. Other Agents.- VII. Subcellular Localization of Cyclic AMP.- VIII. Effects of Guanine Nucleotides.- C. Phosphodiesterase.- I. Effects of Inhibitors.- II. Properties of the Enzymes.- III. Release from Platelets.- IV. Regulatory Role of Phosphodiesterase.- V. Uses of Phosphodiesterase Inhibitors in Thrombosis.- D. Effects of Cyclic AMP on Platelet Function.- I. Direct Effects.- II. Protein Kinases.- III. Phosphorylation of Endogenous Substrates.- E. Cyclic GMP.- I. Properties of Platelet Guanylate Cyclase.- II. Control of Cyclic GMP Levels in Intact Platelets.- F. Changes in Cyclic AMP Metabolism in Disease.- References.- 36 Cyclic Nucleotides in the Immune Response.- Overview.- A. Introduction.- B. Components of the Cyclic Nucleotide System in Lymphoid Tissue..- I. Cyclic Nucleotide Levels.- II. Adenylate Cyclase and Guanylate Cyclase.- III. Phosphodiesterase.- IV. Protein Kinase Activity.- V. Phosphoprotein Phosphatase.- VI. Summary.- C. Lymphocyte Activation.- I. Biochemical Changes in Activated Lymphocytes.- II. Measurement of Lymphocyte Activation.- III. Alterations in Cyclic Nucleotides in Lectin Activated Lymphocytes.- IV. Adenylate Cyclase Activity in Isolated Subcellular Fractions From Human Peripheral Blood Lymphocytes.- V. Cyclic AMP Binding to Lymphocyte Plasma Membranes.- VI. Protein Phosphorylation in Intact Lymphocytes.- VII. Protein Kinase Activity in Lymphocyte Plasma Membranes.- VIII. Summary.- D. Cyclic GMP in Lymphocyte Activation.- E. Cyclic Nucleotides in Lymphocyte-Mediated Cytotoxicity.- F. Cyclic AMP in Proliferating Thymocytes.- G. Conclusions.- References.- 37 The Role of Cyclic Nucleotides in Invertebrates.- Overview.- A. Introduction.- B. Serotonin-Cyclic Nucleotide Interactions.- I. Molluscs.- 1. Nerve Tissue.- 2. Heart.- 3. Gill.- 4. Buccal Muscles.- 5. Catch Muscles.- II. Insects.- 1. Salivary Gland.- 2. Nerve Tissue.- 3. Muscle.- 4. Malphigian Tubule.- III. Crustacea.- 1. Heart.- 2. Limb Muscles.- 3. Eyestalk (Hormone Release).- IV. Trematodes.- 1. Liver Fluke.- 2. Other Trematodes.- C. Octopamine-Cyclic Nucleotide Interactions.- I. Molluscs.- 1. Nerve Tissue.- 2. Muscle.- II. Insects.- 1. Photogenic Tissue.- 2. Nerve and Muscle.- 3. Metabolic Effects.- 4. Relationship to Pesticide Action.- III. Crustacea.- IV. Arachnids.- D. Dopamine-Cyclic Nucleotide Interactions.- I. Molluscs.- 1. Nerve Tissue.- 2. Gill.- 3. Muscle.- II. Insects.- 1. Salivary Gland.- 2. Other Tissues.- III. Crustacea.- 1. Nerve Tissue.- 2. Muscle.- E. Peptide — Cyclic Nucleotide Interactions.- I. Molluscs.- II. Insects.- III. Crustacea.- F. Other Roles For Cyclic Nucleotides in Invertebrates.- I. Sponges.- II. Coelenterates.- III. Nematodes.- IV. Annelids.- References.