Cyclic Nucleotides: Part II: Physiology and Pharmacology

ISBN-13: 9783642683954 / Angielski / Miękka / 2011 / 888 str.

P. D. Kebabian;M. D. Nathanson

Opis

Cyclic nucleotides are intimately involved in the consequences of either stimulation or blockade of receptors; therefore, an understanding of the biochemistry of cyclic nucleotides ought to be important for pharmacologists. Pharmacology is a science that among other things investigates chemical compounds that affect the physiology of cells, tissues and organs. Frequently pharmacologists account for the effect of low concentrations of a drug upon a tissue by invoking the presence of a receptor upon the surface of the cell. Traditional pharmacologists excelled at identifying and classifying the properties of receptors. A. J. CLARK'S monograph in the earlier series of the Handbook of Experimental Pharmacology (CLARK 1937) summarized the mathematics underlying the traditional pharmacological approach towards receptors. By its nature, however, classic pharmacology provided little useful information about the intracellular events occurring as a consequence of occupying a receptor; for example, ALQUIST (1948) identified the beta-adrenocep- tor, but he did not provide any insight into how stimulation of the receptor produces tissue-specific physiological responses. The discovery of cyclic AMP by RALL and SUTHERLAND (see RALL, Vol. I) led to biochemical investigations of many different receptors (including ALQUIST'S beta-adrenoceptor) that share a cyclic nucleotide as a common factor in the biochemical mechanisms that translate the occupancy of receptors into physiological effects. Ten years ago, in the introduction to their monograph on cyclic nucleotides, ROBISON et al. (1971) commented on the rapid growth of interest in cyclic nucleotides over the preceding years.

Spis treści

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.