Mechanisms and Consequences of Proton Transport
Edited by T Urushidani, J G Forte, G Sachs. Amsterdam: Kluwer, 2002, b/w, pp 372. ISBN 1-4020-7059-4
For someone who attended one of the early proton transport meetings and who lived through the era of the discovery of histamine H2 receptor antagonists and proton pump inhibitors, this volume makes fascinating reading. The elegant application of modern biochemical and molecular biology techniques has increased our knowledge of the intimate working of the proton pump in a remarkable manner. The book, written by key players in the field, describes, to use a hackneyed phrase, the cutting edge research that is being undertaken. The contributions are not restricted to proton transport but address the K+ and Cl− channels in the parietal cell and the role of Ca2+ in the secretory process. In the latter context, it is interesting that our knowledge of the structure of the gastric H+/K+ ATPase has depended heavily on studies of the crystal structure of the calcium pump of the sarcoplasmic reticulum. New, to the reviewer at least, is the existence of parchorin, a chloride intracellular channel related protein which appears to play an important role in the regulated movement of body fluid via Cl− transport in a range of tissues, including the gastric mucosa, salivary gland, and kidney. As an old acid inhibitory man, I viewed, at least initially, a role for Helicobacter pylori in the aetiology of peptic ulcer with some scepticism. However, I found the current chapters on this bacterium absorbing, particularly in the cunning ways it combats the low intragastric pH by, for example, downregulation of H+/K+ ATPase gene expression. Similarly, the fact that the H+/K+ ATPase is the dominant gastric autoantigen in H pylori infection has important implications for our understanding of autoimmune gastritis and possibly gastric cancer.
In their preface, the editors state that the field is still filled with a multitude of potential targets for drug development but it is not exactly clear what they have in mind. The chapter on inhibition of acid secretion using a myosin light chain kinase inhibitor applied locally is scientifically interesting but do we really need another antisecretory drug to add to the already highly effective armamentarium of H2 antagonists and proton pump inhibitors? The same argument applies to potential inhibitors of the potassium channel. Are there pathological states associated with the non-gastric H+/K+ ATPase found in the kidney and colon? Probably not, as they play an important role in the normal maintenance of body K+ homeostasis.
As is inevitable with a book based on presentations at a conference, some of the chapters are short and drop the reader almost immediately into the detailed science without much background introduction. The first chapter is excellent, setting the scene for the research based chapters that follow, although a little more discussion on the proton pump inhibitors both of the covalent class and K+ competitive-type would have been useful.
In these days of “all singing, all dancing” computer enhanced images, the cover of the book is disappointing and far from eye catching. The book is obviously required reading for those actively involved in the field of proton transport. Whether it will appeal to a broader audience is less clear.