In the first 20 years that followed the purinergic signalling hypothesis in 1972, most scientists were sceptical about its validity, largely because ATP was so well established as an intracellular molecule involved in cell biochemistry and it seemed unlikely that such a ubiquitous molecule would act as an extracellular signalling molecule. However, after the receptors for ATP and adenosine were cloned and characterized in the early 1990s and ATP was established as a synaptic transmitter in the brain and sympathetic ganglia, the tide turned. More recently it has become clear that ATP is involved in long-term (trophic) signalling in cell proliferation, differentiation and death, in development and regeneration, as well as in short-term signalling in neurotransmission and secretion. Also, important papers have been published showing the molecular structure of P2X receptors in primitive animals like Amoeba and Schistosoma, as well as green algae. This has led to the recognition of the widespread nature of the purinergic signalling system in most cell types and to a rapid expansion of the field, including studies of the pathophysiology as well as physiology and exploration of the therapeutic potential of purinergic agents. In two books, Geoffrey Burnstock and Alexej Verkhratsky have aimed at drawing together the massive and diverse body of literature on purinergic signalling. The topic of this first book is purinergic signalling in the peripheral and central nervous systems and in the individual senses. In a second book the authors focus on purinergic signalling in non-excitable cells, including those of the airways, kidney, pancreas, endocrine glands and blood vessels. Diseases related to these systems are also considered.

T cells play a vital role mediating adaptive immunity, a specific acquired resistance to an infectious agent produced by the introduction of an antigen. There are a variety of T cell types with different functions. They are called T cells, because they are derived from the thymus gland. This volume discusses how T cells are regulated through the operation of signaling mechanisms. Topics covered include positive and negative selection, early events in T cell receptor engagement, and various T cell subsets.

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.

ATP, the intracellular energy source, is also an extremely important cell–cell signalling molecule for a wide variety of cells across evolutionarily diverse organisms. The extracellular biochemistry of ATP and its derivatives is complex, and the multiple membrane receptors that it activates are linked to many intracellular signalling systems. Purinergic signalling affects a diverse range of cellular phenomena, including ion channel function, cytoskeletal dynamics, gene expression, secretion, cell proliferation, differentiation and cell death. Recently, this class of signalling molecules and receptors has been found to mediate communication between neurons and non-neuronal cells (glia) in the central and peripheral nervous systems. Glia are critical for normal brain function, development and response to injury. Neural impulse activity is detected by glia and purinergic signalling is emerging as a major means of integrating functional activity between neurons, glia and vascular cells in the nervous system. These interactions mediate effects of neural activity on the development of the nervous system and in association with injury, neurodegeneration, myelination and cancer. Bringing together contributions from experts in diverse fields, including glial biologists, neurobiologists and specialists in purinergic receptor structure and pharmacology, this book considers how extracellular ATP acts to integrate communication between different types of glia, and between neurons and glia. Beginning with an overview of glia and purinergic signalling, it contains detailed coverage of purine release, receptors and reagents, purinergic signalling in the neural control of glial development, glial involvement in information processing, and discussion of the interactions between neurons and microglia.

This is an overview of the fast-moving field of purinergic signalling through adenosine and ATP receptors. - Authors are the leading authorities in their fields - Subject matter is important for understanding tissue protection - Subject matter is of intense interest for new drug development

This volume aims to cover all major methodological aspects of research into purinergic signaling and to provide a foundation for studying them at molecular, biochemical, pharmacological, and physiological levels. Chapters guide readers through current knock-out and knock-in mouse models, in silico modeling, knock down purinoceptor expression, bioluminiscence resonance energy transfer, enzyme-based biosensors, recording P2X receptor electrophysiology, controlling P2X receptors by optogenetics, inflammasome activation, leukocyte migration, and cell adhesion. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Purinergic Signaling: Methods and Protocols will provide a sound basis for molecular, cellular, and physiological research into purinergic signaling in health and disease and will spark interest in this fascinating signaling process among researchers in many different and unrelated disciplines.

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.