This book explores several subtypes of muscarinic receptors that modulate smooth muscle activity. Main topics include a classification of muscarinic receptors, biochemical responses that occur in smooth muscle, the role of muscarinic receptors in the function of gastrointestinal and genitourinary smooth muscle, and prejunctional muscarinic receptors in smooth muscle. Discussions cover the current state of research and are intended to generate further research into the design of novel therapeutics for disorders of smooth muscle function.
This book is a compendium of the latest electrophysiological research on smooth muscles from an international collection of authors. It includes recent discoveries in calcium stores and their relationship to contraction and to electrical changes in the membrane. A major section of the book concentrates on calcium release mechanisms in the cell, their control, and the consequences of calcium release in the cell for membrane events. Smooth Muscle Excitation also covers the effects of chemicals released from adjacent cells. Key Features * State-of-the-art volume that represents a synopsis of all work currently being undertaken in this area throughout the world * Content covers both basic and clinical research * Provides a range of drug development studies * Presents contributions from many internationally recognized smooth muscle physiologists
In this second edition of Post-Genomic Cardiology, developing and new technologies such as translational genomics, next generation sequencing (NGS), bioinformatics, and systems biology in molecular cardiology are assessed in light of their therapeutic potential. As new methods of mutation screening emerge, both for the genome and for the “epigenome, comprehensive understanding of the many mutations that underlie cardiovascular diseases and adverse drug reactions is within our reach. This book, written by respected cardiologist José Marín-García, features discussion on the Hap-Map: the largest international effort to date aiming to define the differences between our individual genomes. This unique reference further reviews and investigates genome sequences from our evolutionary relatives that could help us decipher the signals of genes, and offers a comprehensive and critical evaluation of regulatory elements from the complicated network of the background DNA. Offers updated discussion of cutting-edge molecular techniques including new genomic sequencing / NGS / Hap-Map / bioinformatics / systems biology approaches Analyzes mitochondria dynamics and their role in cardiac dysfunction, up-to-date analysis of cardio-protection, and cardio-metabolic syndrome Presents recent translational studies, gene therapy, transplantation of stem cells, and pharmacological treatments in CVDs
Muscarinic acetylcholine receptors have played a key role in the advancement of knowledge of pharmacology and neurotransmission since the inception of studies in these fields, and the effects of naturally occurring drugs acting on muscarinic receptors were known and exploited for both therapeutic and non-therapeutic purposes for hundreds of years before the existence of the receptors themselves was recognized. This volume presents a broad yet detailed review of current knowledge of muscarinic receptors that will be valuable both to long-time muscarinic investigators and to those new to the field. It describes the detailed insights that have been obtained on the structure, function, and cell biology of muscarinic receptors. This volume also describes physiological analyses of muscarinic receptors and their roles in regulating the function of the brain and of a variety of peripheral tissues. This volume shows how the study of muscarinic receptors continues to provide new and surprising insights not just to the cholinergic system but to the broad areas of neurobiology, cell biology, pharmacology, and therapeutics.
The differentiation between the muscarinic and the nicotinic ef fects of acetylcholine led to the subdivision of the cholinergic ner vous system into two categories. Further studies showed that stimu lating and inhibiting muscarinic effects could be demonstrated in different organs. For instance, gastric secretion and gastrointestinal motility are stimulated, while heart rate and the vascular muscula ture are inhibited. For decades, it could not be determined whether the various ef fects were mediated by different subgroups of muscarinic receptors, but eventually, with the availability of agonists and antagonists to muscarinic receptors, and using various techniques, the existence of at least two such subgroups could be ascertained . . Mt receptors are defined by their high affinity for the antagonist pirenzipine in comparison to M2 receptors. This subdivision of muscarinic receptors has since been proved beyond doubt by experi ments in vivo and in vitro, by receptor binding studies, by histoauto radiography, and by electrophysiological studies. However, these different classes of muscarinic receptors have not been found to relate to different types of effects; instead both excit atory and inhibitory effects appear to be linked to each class. For ex ample, excitation of gut motility and inhibition of cardiac contrac tile activities both appear to be mediated by M2 receptors, while ex citation of some nerves in sympathetic ganglia and inhibition of some myenteric nerves may be mediated by M receptors.
The costs associated with a drug's clinical trials are so significant that it has become necessary to validate both its safety and efficacy in animal models prior to the continued study of the drug in humans. Featuring contributions from distinguished researchers in the field of cognitive therapy research, Animal Models of Cognitive Impairmen
Three distinct types of contractions perform colonic motility functions. Rhythmic phasic contractions (RPCs) cause slow net distal propulsion with extensive mixing/turning over. Infrequently occurring giant migrating contractions (GMCs) produce mass movements. Tonic contractions aid RPCs in their motor function. The spatiotemporal patterns of these contractions differ markedly. The amplitude and distance of propagation of a GMC are several-fold larger than those of an RPC. The enteric neurons and smooth muscle cells are the core regulators of all three types of contractions. The regulation of contractions by these mechanisms is modifiable by extrinsic factors: CNS, autonomic neurons, hormones, inflammatory mediators, and stress mediators. Only the GMCs produce descending inhibition, which accommodates the large bolus being propelled without increasing muscle tone. The strong compression of the colon wall generates afferent signals that are below nociceptive threshold in healthy subjects. However, these signals become nociceptive; if the amplitudes of GMCs increase, afferent nerves become hypersensitive, or descending inhibition is impaired. The GMCs also provide the force for rapid propulsion of feces and descending inhibition to relax the internal anal sphincter during defecation. The dysregulation of GMCs is a major factor in colonic motility disorders: irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and diverticular disease (DD). Frequent mass movements by GMCs cause diarrhea in diarrhea predominant IBS, IBD, and DD, while a decrease in the frequency of GMCs causes constipation. The GMCs generate the afferent signals for intermittent short-lived episodes of abdominal cramping in these disorders. Epigenetic dysregulation due to adverse events in early life is one of the major factors in generating the symptoms of IBS in adulthood.
