We proudly present the first book to integrate all aspects of purinergic signaling in the respiratory system. The first chapters introduce basic notions of purinergic pharmacology and metabolism, which allows readers from all scientific backgrounds to fully grasp the importance of these signaling networks for airway defenses, including mucociliary clearance and inflammatory responses. Then, chapters are devoted to the groundbreaking discovery that chronic respiratory diseases, including asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD), present specific aberrances in purinergic signaling which essentially drive lung complications. The last chapters describe the animal models used to investigate purinergic signaling in respiratory diseases, and the therapeutic applications developed by the pharmaceutical industry based on receptor agonists/antagonists and metabolic correctors. This highly comprehensive manuscript constitutes an invaluable tool for beginners and experts to follow the rapidly evolving research field of purinergic signaling. Furthermore, the critical analysis of past clinical protocols should facilitate the identification of potent therapeutic targets, and provide a better understanding of the data acquired in current clinical trials.

We proudly present the first book to integrate all aspects of purinergic signaling in the respiratory system. The first chapters introduce basic notions of purinergic pharmacology and metabolism, which allows readers from all scientific backgrounds to fully grasp the importance of these signaling networks for airway defenses, including mucociliary clearance and inflammatory responses. Then, chapters are devoted to the groundbreaking discovery that chronic respiratory diseases, including asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD), present specific aberrances in purinergic signaling which essentially drive lung complications. The last chapters describe the animal models used to investigate purinergic signaling in respiratory diseases, and the therapeutic applications developed by the pharmaceutical industry based on receptor agonists/antagonists and metabolic correctors. This highly comprehensive manuscript constitutes an invaluable tool for beginners and experts to follow the rapidly evolving research field of purinergic signaling. Furthermore, the critical analysis of past clinical protocols should facilitate the identification of potent therapeutic targets, and provide a better understanding of the data acquired in current clinical trials.

This presentation describes various aspects of the regulation of tissue oxygenation, including the roles of the circulatory system, respiratory system, and blood, the carrier of oxygen within these components of the cardiorespiratory system. The respiratory system takes oxygen from the atmosphere and transports it by diffusion from the air in the alveoli to the blood flowing through the pulmonary capillaries. The cardiovascular system then moves the oxygenated blood from the heart to the microcirculation of the various organs by convection, where oxygen is released from hemoglobin in the red blood cells and moves to the parenchymal cells of each tissue by diffusion. Oxygen that has diffused into cells is then utilized in the mitochondria to produce adenosine triphosphate (ATP), the energy currency of all cells. The mitochondria are able to produce ATP until the oxygen tension or PO2 on the cell surface falls to a critical level of about 4–5 mm Hg. Thus, in order to meet the energetic needs of cells, it is important to maintain a continuous supply of oxygen to the mitochondria at or above the critical PO2 . In order to accomplish this desired outcome, the cardiorespiratory system, including the blood, must be capable of regulation to ensure survival of all tissues under a wide range of circumstances. The purpose of this presentation is to provide basic information about the operation and regulation of the cardiovascular and respiratory systems, as well as the properties of the blood and parenchymal cells, so that a fundamental understanding of the regulation of tissue oxygenation is achieved.

The study of carbonic anhydrase has spanned multiple generations of scientists. Carbonic anhydrase was first discovered in 1932 by Meldrum and Roughton. Inhibition by sulfanilamide was shown in 1940 by Mann and Keilin. Even Hans Krebs contributed to early studies with a paper in 1948 showing the relationship of 25 different sulfonamides to CA inhibition. It was he who pointed out the importance of both the charged and uncharged character of these compounds for physiological experiments. The field of study that focuses on carbonic anhydrase (CA) has exploded in recent years with the identification of new families and isoforms. The CAs are metalloenzymes which are comprised of 5 structurally different families: the alpha, beta, gamma, and delta, and epsilon classes. The alpha class is found primarily in animals with several isoforms associated with human disease. The beta CAs are expressed primarily in plants and are the most divergent. The gamma CAs are the most ancient. These are structurally related to the beta CAs, but have a mechanism more similar to the alpha CAs. The delta CAs are found in marine algae and diflagellates. The epsilon class is found in prokaryotes in which it is part of the carboxysome shell perhaps supplying RuBisCO with CO2 for carbon fixation. With the excitement surrounding the discovery of disease-related CAs, scientists have redoubled their efforts to better understand structure-function relationships, to design high affinity, isotype-specific inhibitors, and to delineate signaling systems that play regulatory roles over expression and activity. We have designed the book to cover basic information of mechanism, structure, and function of the CA families. The authors included in this book bring to light the newest data with regard to the role of CA in physiology and pathology, across phylums, and in unique environmental niches.

This book aims to provide a brief update on the functions of purinergic receptors in various systems, in addition to the signaling pathway activated to mediate these functions. We address the influence of hypoxia by modulating the activity of these receptors under physiological and pathophysiological conditions. Additionally, we describe the mechanisms of induction of pain and inflammation in different systems. Finally, the book discusses some of the main bioinformatics tools currently used to improve or discover new prototypes capable of selectively acting on these receptors with estimated parameters of satisfactory solubility and toxicity for possible commercial implementation.

The imbalance between the production of reactive oxygen species (ROS) and antioxidant defenses determines a state known as oxidative stress. Higher levels of pro-oxidants compared to antioxidant defenses may generate oxidative damage, which, in turn, may lead to modifications in cellular proteins, lipids, and DNA, reducing functional capacity and increasing the risk of diseases. Nevertheless, the clearance of harmful reactive chemical species is achieved by the antioxidant defense systems. These protection systems are referred to as the first and second lines of defense and comprise the classic antioxidants, enzymatic and nonenzymatic defenses, including glutathione. This book presents and discusses the advancement of research on health and diseases and their underlying mechanisms, exploring mainly aspects related to the glutathione antioxidant system.

Membrane Transporters in the Pathogenesis of Cardiovascular and Lung Disorders, Volume 83, the latest release in the Current Topics in Membranes series, highlights new advances in the field, with this volume presenting chapters from recognized experts on topics such as cardiotonic steroids, Na+, K+ pumps and vascular fibrosis, purinergic signaling in the lung, structural models of a2-subunit N-termini and binding interfaces, ubiquitous and cell type-specific transcriptomic changes triggered by dissipation of monovalent cation gradients, the Na, K-ATPase alpha2 isoform in cardiovascular pathologies, the role of cell swelling and volume-sensitive ion channels in stroke pathology, structure-function relationships in the renal NaCl cotransporter, and more. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in the Current Topics in Membranes series - Includes the latest information on membrane ion transporters

A number of chronic respiratory diseases including chronic bronchitis, asthma, cystic fibrosis and bronchiectasis are characterized by mucus hypersecretion. Following damage to the airway epithelium, a repair process of dedifferentiation, regenerative proliferation and redifferentiation takes place that is invariably accompanied by mucus hypersecretion as a key element in the host defence mechanism. In chronic respiratory diseases, however, excessive mucus production leads to a pathological state with increased risk of infection, hospitalization and morbidity. An understanding of the mechanisms that underlie and maintain this hypersecretory phenotype is therefore crucial for the development of rational approaches to therapy. Despite a high and increasing prevalence and cost to healthcare services and society, mucus hypersecretion in chronic respiratory disease has received little attention until recently, probably because of the difficulties inherent in studying this pathology. Only in the last few years have some of the genes involved in mucus secretion been characterized. The recent availability of genomic sequence information and specific antibodies has led to an explosion of interest in this area making this publication particularly timely. This book draws together contributions from an international and interdisciplinary group of experts, whose work is focused on both basic and clinical aspects of the problem. Coverage includes epidemiology, airways infection and mucus hypersecretion, the genetics and regulation of mucus production, models of mucus hypersecretion, and the implications of new knowledge for the development of novel therapies.

Since their discovery approximately 25 years ago, adenosine receptors have now emerged as important novel molecular targets in disease and drug discovery. These proteins play important roles in the entire spectrum of disease from inflammation to immune suppression. Because of their expression on a number of different cell types and in a number of different organ systems they play important roles in specific diseases, including asthma, rheumatoid arthritis, Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, heart disease, stroke, cancer, sepsis, and obesity. As a result of intense investigations into understanding the molecular structures and pharmacology of these proteins, new molecules have been synthesized that have high specificity for these proteins and are now entering clinical trials. These molecules will define the next new classes of drugs for a number of diseases with unmet medical needs.

This book details advances in research regarding cilia, mucus, and mucociliary clearance, examining changes in mucus expression and goblet cell metaplasia, and assessing the ability of the mucociliary system to respond to abnormalities. Recognizes that cilia and dynein arms play pivotal roles in developing mammalian embryos! Examines the rol