The most comprehensive and conceptual one-volume treatment of this field available and the first to emphasize the cellular and molecular aspects of gut peptide biology. Authored by an array of internationally distinguished scientists, it deals with issues of peptide localization and biosynthesis in gastrointestinal cells, mechanisms of peptide release and inactivation and the nature of peptide receptors. The breadth and readability make it an invaluable reference source for scientists in all disciplines interested in any aspect of brain-gut peptides.
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1 Localization and Colocalization of Gastrointestinal Peptides.- A. Introduction.- B. Coexistence of Messengers.- C. Endocrine and Paracrine Cells.- I. Stomach.- II. Small Intestine.- III. Large Intestine.- IV. Coexistence of Peptides in Gut Endocrine Cells.- D. Enteric Neurons.- I. Distribution of Peptide-Containing Nerve Fibers in the Digestive Tract.- II. Projections of Enteric Neurons in the Rat.- 1. Myenteric Neurons.- 2. Submucous Neurons.- III. Coexistence of Peptides in Enteric Neurons.- References.- 2 Regulation of Gastrointestinal Peptide Hormone Gene Expression.- A. Introduction.- B. Gene Structure.- C. RNA Polymerase II.- D. Transcriptional Regulation Overview.- I. DNA Elements.- II. Transcription Factors.- 1. General Transcription Factors.- 2. Regulated Transcription Factors.- 3. Modulation of Transcription Factor Activity.- III. Transcriptional Repression.- IV. Genes Lacking TATA Elements.- E. Analysis of Gene Expression.- I. RNA Quantitation.- II. Promoter Studies.- F. Regulation of Specific Hormone Gene Expression.- I. Preface.- II. Gastrin/Cholecystokinin Family.- 1. Gastrin: Background.- 2. Luminal Regulation of Gastrin Gene Expression.- 3. Islet Cell Gastrin Expression.- 4. Gastrin Promoter Analysis.- a) Studies in Pituitary Cell Lines.- b) Studies in Islet Cells.- 5. Cholecystokinin: Background.- 6. Cholecystokinin Gene Regulation: RNA Quantitation.- 7. Cholecystokinin: Promoter Analysis.- III. Somatostatin.- 1. Somatostatin Gene Regulation.- 2. Model of cAMP Regulation.- 3. Tissue Specific Expression.- IV. Glucagon.- V. Secretin.- VI. Motilin.- G. Conclusion.- References.- 3 Post-Translational Processing of Regulatory Peptides.- A. Introduction.- B. General Design of Processing Systems.- I. Active Peptide Stored in Secretory Vesicles.- II. Active Peptide Released Constitutively.- III. Precursor Activated in or Near Cell of Origin.- 1. Precursor Stored Intracellularly.- 2. Precursor Anchored to Cell Surface.- IV. Precursor Activated in the Interstitial Space or Blood.- V. Precursor Activated at Target or by Other Cells.- 1. Precursor Stored Outside Target.- 2. Precursor Stored Inside Target.- VI. Mixed Systems.- C. Intracellular Trafficking and Processing Pathways.- D. Processing Sites and General Mechanisms.- I. Two-Step Processing.- II. Dibasic, Monobasic and Nonbasic Sites.- III. Conformation and Consensus Features.- IV. Sequentially Ordered Reactions.- V. Tissue-Specific Processing.- E. Enzymes Involved in the Processing of Prohormones.- I. Dibasic Residue-Specific Endoproteases.- II. Monobasic Residue-Specific Endoproteases.- III. Tetrabasic Residue-Specific Endoproteases.- IV. Exopeptidases.- V. Enzymes Involved in N- and C-Terminal Modification.- 1. Acetyltransferase.- 2. Glutaminyl Cyclase.- 3. Peptidylglycine a-Amidating Monooxygenase.- VI. Enzymes Involved in Sulfation and Phosphorylation.- 1. Tyrosine Sulfation Enzyme.- 2. Serine Phosphorylating Enzymes.- F. Processing of Specific Prohormones.- I. Yeast Pheromones.- II. Proopiomelanocortin.- III. Gastrointestinal Hormones.- 1. Glucagon and Related Peptides.- 2. Cholecystokinin.- 3. Gastrin.- 4. Somatostatin.- 5. Neurotensin and Neuromedin-N.- 6. Pancreatic Polypeptide.- G. Conclusion.- References.- 4 Regulation of Peptide Secretion from Gastroenteric Endocrine Cells.- A. Introduction.- B. Gastroenteric Endocrine Cells.- I. Localization.- II. Methods for Studying Peptide Release.- C. Neurotransmitter and Peptide Regulation of Release.- I. Acetylcholine.- II. Norepinephrine.- III. Somatostatin.- IV. Gastrin-Releasing Peptide and Bombesin.- V. Gastrin and Cholecystokinin.- D. Nutrient Regulation of Peptide Release.- I. Proteins and Amino Acids.- II. Fatty Acids.- E. Regulation of Release by Luminal pH.- F. Summary.- References.- 5 Peptide Receptors and Signal Transduction in the Digestive Tract.- A. Introduction.- B. General Considerations and Methodology.- I. Receptor Concept and General Properties.- II. Methods for Study of Receptors.- 1. Tissue Preparations.- 2. Radiolabeled Ligand.- 3. Separation of Bound and Unbound Ligand.- III. Molecular Characterization and Purification.- IV. Receptor Cloning Strategies.- C. Signal Transduction by Receptors.- I. Adenylyl Cyclase: Cyclic AMP Pathway.- II. Phosphatidyl Inositol Signaling.- D. Peptide Receptors in the Digestive Tract.- I. Vasoactive Intestinal Peptide.- II. Galanin.- III. Neurotensin.- E. Conclusion and Perspectives.- References.- 6 Proteolytic Inactivation of Neurohormonal Peptides in the Gastrointestinal Tract.- A. Introduction.- B. Proteolytic Enzymes Implicated in the Inactivation of Neurohormonal Peptides in the Gastrointestinal Tract.- I. Endopeptidases.- 1. Endopeptidase 24.11.- 2. Endopeptidase 24.15.- 3. Endopeptidase 24.16.- II. Exopeptidases.- 1. Peptidyl Dipeptidase A.- 2. Aminopeptidases.- 3. Dipeptidyl Aminopeptidase IV.- 4. Carboxypeptidases.- C. Pathways of Proteolytic Inactivation of Some Gastrointestinal Hormones.- I. Neurotensin.- II. Gastrin.- III. Cholecystokinin.- IV. Somatostatin.- D. Pathways of Proteolytic Inactivation of Some Gastrointestinal Neuropeptides.- I. Tachykinins.- II. Enkephalins.- III. Vasoactive Intestinal Polypeptide.- E. Conclusion.- References.- 7 Peptidergic Regulation of Gastric Acid Secretion.- A. Introduction.- B. Acid Secretory Control Mechanisms In Vivo.- I. Extrinsic Innervation and Central Control.- II. Intrinsic Innervation.- III. Cephalic and Gastric Phases of Secretion.- 1. Gastrin Release Mechanisms.- 2. Effects of Other Peptides.- IV. Intestinal Factors.- V. Inhibitory Phases of Acid Secretion.- 1. Cephalic Influences.- 2. Antral and Fundic Mechanisms.- 3. Intestinal Inhibitory Mechanisms.- a) Secretin.- b) Cholecystokinin.- c) Gastric Inhibitory Polypeptide.- d) Somatostatin.- e) Neurotensin.- f) Glucagon-Like Peptides.- g) Peptide YY.- 4. Neuropeptide Inhibitors.- a) Substance P.- b) Galanin.- C. Peptide Effects on Isolated Cells.- I. Parietal Cells.- 1. Peptide Activation Mechanisms.- a) Gastrin.- b) Effects of Other Peptides.- 2. Peptide Inhibitory Mechanisms.- a) Somatostatin.- b) Epidermal Growth Factor.- c) Other Inhibitory Peptides.- II. Antral G Cells.- III. Fundic and Antral D Cells.- IV. Histamine-Containing Cells.- References.- 8 Peptides and Enteric Neural Activity.- A. Introduction.- B. Electrophysiology of Enteric Nerves.- C. Actions of Peptides on Enteric Nerves.- I. Tachykinin Peptides.- 1. Tachykinin Peptides in Enteric Nerves.- 2. Tachykinins Depolarize Enteric Neurons.- 3. Tachykinins Decrease Resting Potassium Conductance (GK).- 4. Tachykinin-Induced Depolarizations Associated with a Conductance Increase.- 5. Tachykinin Receptors on Enteric Neurons.- 6. Tachykinin Receptors Coupled to Polyphosphoinositide Hydrolysis.- 7. Synaptic Activation of Tachykinin Receptors.- II. Vasoactive Intestinal Peptide.- 1. Vasoactive Intestinal Peptide Receptors Coupled to GK Decrease.- 2. Vasoactive Intestinal Peptide Receptors May Be Coupled to Adenylate Cyclase in Enteric Nerves.- 3. Synaptic Potentials Mediated by Vasoactive Intestinal Peptide.- III. Calcitonin Gene-Related Peptide.- 1. Calcitonin Gene-Related Peptide Receptors Coupled to GK Decrease.- 2. Transduction Mechanism.- IV. Cholecystokinin.- 1. Cholecystokinin Receptors Coupled to a GK Decrease.- 2. Transduction Mechanism.- 3. Receptors on Enteric Neurons.- 4. Cholecystokinin Facilitates Neurotransmission in Pancreatic and Gallbl…