Gastrointestinal Regulatory Peptides

Since the discovery of the pancreatic secretagogue secretin by W. M. BAYLISS and E. H. STARLING at the inception of the twentieth century, intense interest has focused on numerous, continually expanding classes of small peptides which appear to serve as regulatory molecules in the gastrointestinal tract, brain, and other organ systems. Initially, many of these substances were, like secretin, discovered in functional assays as "factors" or "activities" extractable in minute quantities from tissues or tissue fluids. By the middle of the century, advances in biochemical and immunological methods for the purification, characterization, and quantification of biologically active peptides in organ systems, tissues, and body fluids provided further impetus to this field. It was readily appreciated that small, biologically active peptides were particularly abundant in the digestive tract. Many peptides such as vasoactive intestinal peptide, gastrin, and more recently peptide YY and galanin were in fact originally discovered in and isolated from gut tissue. Moreover, these peptides were found to have profound actions on the gastroenteropancreatic system in vivo and in vitro. During the past 2 decades, information on regulatory peptides has burgeoned as a result of technological refinements in the synthesis of peptides, improved methods for detecting and visualizing peptides and their precursors in cells and tissues from a variety of species, advances in the functional assessment of peptide activity, and the application of molecular biological techniques to the char acterization of peptide gene structure and expression.

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1 Localization and Colocalization of Gastrointestinal Peptides.- A. Introduction.- B. Coexistence of Messengers.- C. Endocrine and Paracrine Cells.- D. Enteric Neurons.- References.- 2 Regulation of Gastrointestinal Peptide Hormone Gene Expression.- A. Introduction.- B. Gene Structure.- C. RNA Polymerase II.- D. Transcriptional Regulation Overview.- E. Analysis of Gene Expression.- F. Regulation of Specific Hormone Gene Expression.- G. Conclusion.- References.- 3 Post-Translational Processing of Regulatory Peptides.- A. Introduction.- B. General Design of Processing Systems.- C. Intracellular Trafficking and Processing Pathways.- D. Processing Sites and General Mechanisms.- E. Enzymes Involved in the Processing of Prohormones.- F. Processing of Specific Prohormones.- G. Conclusion.- References.- 4 Regulation of Peptide Secretion from Gastroenteric Endocrine Cells.- A. Introduction.- B. Gastroenteric Endocrine Cells.- C. Neurotransmitter and Peptide Regulation of Release.- D. Nutrient Regulation of Peptide Release.- 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.- C. Signal Transduction by Receptors.- D. Peptide Receptors in the Digestive Tract.- 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.- C. Pathways of Proteolytic Inactivation of Some Gastrointestinal Hormones.- D. Pathways of Proteolytic Inactivation of Some Gastrointestinal Neuropeptides.- E. Conclusion.- References.- 7 Peptidergic Regulation of Gastric AcidSecretion.- A. Introduction.- B. Acid Secretory Control Mechanisms In Vivo.- C. Peptide Effects on Isolated Cells.- References.- 8 Peptides and Enteric Neural Activity.- A. Introduction.- B. Electrophysiology of Enteric Nerves.- C. Actions of Peptides on Enteric Nerves.- D. Conclusions.- References.- 9 Peptidergic Regulation of Smooth Muscle Contractility.- A. Introduction.- B. Regulation of Smooth Muscle by Peptide Hormones.- C. Regulation of Smooth Muscle by Neural Peptides.- References.- 10 Peptidergic Regulation of Intestinal Electrolyte Transport.- A. Introduction.- B. Transport Models for Absorption and Secretion.- C. Regulation of Intestinal Transport by Peptide Neurohormones.- D. Concluding Remarks.- References.- 11 Peptidergic Regulation of Gastrointestinal Blood Flow.- A. Introduction.- B. Gastrointestinal Peptides.- C. Capsaicin-Sensitive Afferent Nerves.- References.- 12 Peptidergic Regulation of Cell Proliferation Through Multiple Signaling Pathways.- A. Introduction.- B. Growth-Promoting Activities of Neuropeptides in Cultured Cells.- C. Early Signaling Events.- D. Evidence for Growth-Promoting Effects of Neuropeptides In Vivo.- E. Conclusions.- References.- 13 Peptidergic Regulation of Mucosal Immune Function.- A. Introduction.- B. Overview of Immune Function in Gut-Associated Lymphoid Tissue.- C. Peptide Effects on Immune Function.- D. Conclusion.- References.- 14 Pathophysiological Aspects of Gut Peptide Hormones.- A. Introduction.- B. Esophagus.- C. Stomach.- D. Duodenum.- E. Pancreas.- F. Gallstones.- G. Small Bowel.- H. Colon.- J. Gastrointestinal Hormones and Cardiovascular Function.- K. Conclusions.- References.- 15 Gastrointestinal Peptides as Therapeutic Agents and Targets: Past, Present and Future.- A. Introduction.- B. Diagnostic Use of Gastrointestinal Peptides.- C. Peptides as Agonists in Therapeutics.- D. Antagonists of Peptides in Therapy.- E. The Future.- References.