The Brain Within the Gut

Totowa, Humana, 1999, $150.00 (x + 584 pages)ISBN 0-896-03506-9This book represents an attempt to provide a selective, and timely, update for a field of substantial complexity and importance that has clearly come of age. The gastrointestinal tract represents the largest endocrine organ in the body and plays the role of ‘brain’ to control, regulate, and integrate the broad spectrum of digestive events that are so important for nutrient homeostasis and survival of the organism. The editor of this multi-author text, George Greeley, Jr, states in his preface that this field is ‘not young or new’, but has matured to include a diversity of regulatory peptides, receptors and biological signaling systems. Rather than attempt to be comprehensive, he has chosen to focus on a few peptides, their physiology and pathophysiology, and the regulatory mechanisms underlying their actions in the gastrointestinal system. An introduction focuses on the structure and function of the hormone-secreting cells scattered throughout the gut. The volume is divided into three major sections: (1) the biochemistry, pharmacology, and receptor biology of the gastrointestinal endocrine system; (2) regulatory mechanisms relevant to these peptides; and (3) several selected gut peptides themselves.This volume has made an attempt to balance what is known about each aspect of the gastrointestinal endocrine system, from endocrine cells to the secreted peptides and to their receptor targets. The most extensive treatment is at the level of the peptides themselves, with only a single introductory chapter dealing with the endocrine cells and with only two chapters devoting substantial focus on receptors.Different groups might benefit from reading this volume. Students and new investigators could obtain a representative glimpse of diverse peptides and receptors, although lack of a global framework or clear organization makes perspective somewhat difficult. Selected chapters are outstanding and appropriate for the most experienced investigators; however, inconsistency in depth of detail and the extent and timeliness of referencing might limit the enthusiasm for such a reader. Finally, the substantial expense of this volume is another component affecting its attractiveness.Part I includes outstanding contributions on the mechanisms of receptor desensitization (Chapter 2 by Stephan Bohm, Eileen F. Grady, and Nigel W. Bunnett) and descriptions of some relevant G-protein-coupled receptors (Chapter 4 by Marc Laburthe, Alain Couvineau and Thierry Voisin). Chapter 4 focuses on the VIP/PACAP and PYY/NPY/PP receptor families. While both are covered well, their selection and grouping together reflects the unusual organization of the volume.Part II provides an overview of current concepts regarding the physiological effects and regulatory mechanisms of specific gastrointestinal hormones, and their presumed roles in certain pathological processes. In this section, Chapter 5 (by Helen E. Raybould) focuses on the effect of cholecystokinin (CCK) to delay gastric emptying. Data from animal studies have demonstrated that CCK has both direct effects on gastric smooth muscle and on intrinsic neurons, and serves as a chemical ‘sensor’ that transmits information of luminal content via a capsaicin-sensitive vagal afferent pathway. The author provides a comprehensive overview of the experimental data that support a neurotransmitter role for CCK. She correctly states in her conclusions that most of these studies have been performed in animal models and, to date, have never been confirmed in humans.The next chapter attempts to shed some light on the effect of aging on gut hormones and gut functions (Tien C. Ko and James C. Thompson). It is meticulously thorough in describing species-related differences and regional variations in age-related effects on hormone content and function. Unfortunately, by doing so, the authors lose clarity and structure in the amalgam of available (and all too often contradictory) data.The eighth chapter (Alan W. Spannagel and Gary M. Green) gives an excellent overview of the current status of research into intraluminal regulatory mechanisms that control CCK secretion. Multiple illustrations and diagrams provide additional information for the reader, facilitating a better understanding of mechanistically important pathways and experimental conditions.Chapter 9 by David C. Whitcomb focuses on the different levels of control of exocrine pancreatic secretion, including neuronal and hormonal control systems and their integration. It provides an excellent overview of both old and new information regarding the role of the different stimulatory and inhibitory hormones. The author also emphasizes the importance of vagal extrinsic innervation for exocrine pancreatic function, thereby stressing the importance of the dorsal vagal complex and its different anatomical components. Also highlighted are recent data showing the presence and functional importance of duodenopancreatic nerve fibers emanating from the enteric nervous system.The next chapter (Sang K. Park and M. Sue O'Dorisio) reviews neuroendocrine immune interactions in the different hypothalamic–pituitary axes, including those that are of major importance in the intestinal immune tissues. First, the authors provide a general overview of the immune interactions between the hypothalamic–pituitary axis and its key target organs – the liver, the gonads, the thyroid gland, and the major cellular components of the immune response. Second, neuroendocrine–immune interactions in the intestine are described. A complete state-of-the-art review of the role of different neuropeptides (substance P, VIP, somatostatin, NPY and CGRP) in these interactions is given. The obvious importance of this chapter is to provide a better understanding of the mechanisms of new therapeutic strategies that might interfere with, or modify, the immune response in the gut, for example in the treatment of inflammatory bowel diseases.Gastrointestinal hormones not only regulate metabolic and secretory processes, but, as part of the physiologic response to a caloric meal, also exert major effects on aboral transport of luminal contents. They do this by initiating and modulating coordinated peristaltic contractions of the smooth muscle wall of the gastrointestinal tract, resulting in propulsion. In Chapter 11, J.R. Grider and A.E. Fox-Orenstein elegantly describe the role of neuropeptides and hormones in peristalsis. Although a multitude of peptides affects peristalsis in both synergistic and opposite ways, thereby contributing to the high complexity of peristalsis control, the authors succeed in providing sufficient insight in a relatively simplified manner. The abundant graphs and diagrams are clear and self-explanatory.A rather concise Chapter 12 (by Neal E. Seymour and Dana K. Andersen) summarizes novel insights into the role of pancreatic polypeptide (PP) in glucose metabolism. Three sections describe the role of PP in glucose-intolerance secondary to pancreatic destruction (chronic pancreatitis, pancreas resection), the effect of PP on hepatic insulin receptor appearance, and on insulin receptor gene expression. The authors conclude that normal PP secretion is necessary for normal function and expression of hepatic insulin receptors.In the next chapter, the author, Jean-Claude Cuber, focuses on the release mechanisms of three peptides secreted by specialized mucosal cells from the upper small intestine: secretin, CCK and motilin. He also describes briefly the methodological approach for the study of gut peptide release in vitro. Information on motilin is most extensively described, and includes the putative biological actions of this peptide.Chapter 14 (Wolfgang E. Schmidt and Jerzy B. Bojko) provides an excellent review of the most recent insights in the regulation of gastric acid secretion. Multiple figures of proposed models clarify the often complicated textual explanation. This chapter concludes with a section on the clinical pathophysiology of acid secretion, thereby offering the non-gastroenterologist clinician a fine opportunity to become re-acquainted with some of the newer concepts of peptic ulcer disease (e.g. H. pylori).Part III contains six chapters, each covering one specific peptide or family of peptides. These include neurotensin/neuromedin N, glucose-dependent insulinotropic polypeptide (GIP), insulin-like growth factors, proglucagon-derived peptides, islet amyloid polypeptide (IAPP, amylin), adrenomedullin, and finally peptide YY. Each of the six chapters gives a detailed description of structure and expression regulation of the various peptides, their respective physiological role and their receptors.This volume represents a timely reference for selected areas of the exciting and important field of gastrointestinal endocrinology.