Springer protocols feed by Pharmacology/Toxicology 
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This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.Rescue of Defective G Protein-Coupled Receptor Function by Intermolecular Cooperation
G protein-coupled receptors (GPCRs) transduce signals from a wide variety of extracellular stimuli such as ions, photons, odors, tastants, hormones, and neurotransmitters and hence are central players in communication between the cells of multicellular organisms and their environment. Characterization of these receptors at the molecular level has shown that GPCRs form dimers or oligomers (for simplicity, herein called dimers), yet their function is just beginning to emerge. The activation of GPCRs as dimers presents the opportunity for trans-activation of receptors, where a ligand-bound GPCR can change the activity of a ne...
Source: Springer protocols feed by Pharmacology/Toxicology - January 27, 2014 Category: Drugs & Pharmacology Source Type: news
Design of Super-arrestins for Gene Therapy of Diseases Associated with Excessive Signaling of G Protein-Coupled Receptors
Numerous congenital disorders, ranging from night blindness to cancer, are associated with signaling by overactive GPCR mutants. Excessive GPCR signaling also underlies certain acquired pathological conditions. The coupling of most GPCRs to their cognate G proteins is stopped by the natural desensitization mechanism, which includes receptor phosphorylation by GRKs followed by arrestin binding to active phosphoreceptor. Elucidation of the molecular mechanisms of arrestin binding to GPCRs enabled the construction of enhanced arrestins that bind active receptors with higher affinity and even interact with unphosphorylated GPC...
Source: Springer protocols feed by Pharmacology/Toxicology - January 27, 2014 Category: Drugs & Pharmacology Source Type: news
Use of Optogenetic Approaches to Control Intracellular Signaling of G Protein-Coupled Receptors
The tractability of light-activated receptors makes them attractive tools by which to study the brain. They allow for the noninvasive and specific control of neuronal signaling and could allow for the study of receptor pathways that occur faster than the rate of diffusion. Furthermore, with the aid of implantable light devices, light-activated receptors have the potential for use in live animals and later in humans to control and cure G protein-coupled receptor (GPCR) pathways involved in diseases. We will summarize here the latest developments for controlling intracellular signaling pathways by light-activated GPCRs and e...
Source: Springer protocols feed by Pharmacology/Toxicology - January 27, 2014 Category: Drugs & Pharmacology Source Type: news
Viral Infection for G Protein-Coupled Receptor Expression in Eukaryotic Cells
This chapter describes the protocol for the preparation of recombinant adenoviruses and infection of target cells to transiently express G protein-coupled receptors (GPCRs) or other proteins of interest. Adenoviruses are non-enveloped viruses containing a linear double-stranded DNA genome. Their life cycle does not normally involve integration into the host genome, rather they replicate as episomal elements in the nucleus of the host cell, and consequently there is no risk of insertional mutagenesis. Up to 30 kb out of the 35 kb of the wild-type adenovirus genome can be replaced by foreign DNA. Adenoviral vectors are very ...
Source: Springer protocols feed by Pharmacology/Toxicology - January 27, 2014 Category: Drugs & Pharmacology Source Type: news
Importance of G Protein-Coupled Receptor Genetics in Clinical Medicine
Progress in areas of research from the field of G protein-coupled receptor (GPCR) signaling now shows that GPCRs are involved in a broad range of cellular regulatory activities. By virtue of widespread distribution and important roles in cell physiology and biochemistry, GPCRs play multiple important roles in clinical medicine. The understanding of how GPCRs interact with G proteins, effectors, as well as other regulatory proteins has enormous implications for clinical medicine. The rapid progress in determining three-dimensional structures of GPCRs, and more recently their regulators and effectors, has illuminated the sea...
Source: Springer protocols feed by Pharmacology/Toxicology - January 27, 2014 Category: Drugs & Pharmacology Source Type: news
Pharmacogenomics of G Protein-Coupled Receptor Signaling and Other Pathways in Essential Hypertension
Essential hypertension represents a cluster of genetically determined physiological abnormalities that is influenced by environmental factors and the individual’s lifestyle. Essential hypertension is a major public health challenge because it affects one in every three adult Americans and about one billion people worldwide, yet its current treatment is empirical and is focused on the remediation of a physical sign (i.e., high blood pressure [BP]) and not the underlying cause. In spite of the demonstrable utility of antihypertensive therapy, less than 50 % of patients are effectively managed. Surmounting the limitatio...
Source: Springer protocols feed by Pharmacology/Toxicology - January 27, 2014 Category: Drugs & Pharmacology Source Type: news
Exon Sequencing of G Protein-Coupled Receptor Genes and Perspectives for Disease Treatment
G protein-coupled receptors (GPCRs) comprise the largest family of membrane-spanning proteins in humans with approximately 800 members. GPCRs carry out an extensive array of biological functions and are privileged drug targets. Exon sequencing identified several disease-causing loss-of-function and gain-of-function GPCR mutations in patients with rare diseases. Recent large-scale exon sequencing studies revealed the high abundance of rare GPCR mutations in the human population. Many of these rare mutations are suspected to contribute to the risk of common diseases and interindividual and ethnic differences in drug action. ...
Source: Springer protocols feed by Pharmacology/Toxicology - January 27, 2014 Category: Drugs & Pharmacology Source Type: news
Gene Therapy Using G Protein-Coupled Receptors for the Treatment of Cardiovascular Disease
Cardiovascular diseases are the most common cause of death worldwide, and despite advances in treatments, mortality rates still remain elevated. Heart failure prevalence is increasing and accounts for half a million deaths per year in the USA. Thus, there is an urgent need to develop new therapeutic strategies for heart failure patients, and gene therapy certainly is a promising one. Currently, clinical trials using virus-mediated gene transfer of molecular targets involved in heart failure pathophysiology are in progress. G protein-coupled receptors and the GPCR-related signaling molecules have proven to be a valuable pot...
Source: Springer protocols feed by Pharmacology/Toxicology - January 27, 2014 Category: Drugs & Pharmacology Source Type: news
Novel Mechanisms of G Protein-Coupled Receptor Oligomer and Ion Channel Interactions in Nociception
G protein-coupled receptors (GPCRs) represent the largest family of cell surface receptors that are involved in regulating several physiological and behavioral responses in organisms. Indeed, over half of all the approved drugs on the market target GPCRs. Over the past 20 years, several lines of evidence have suggested that GPCRs associate to form oligomeric structures that substantially expand the complexity of signaling processes in vivo. In addition, GPCRs have also been shown to functionally regulate ion channels and help fine-tune neurotransmission. In this review, we will discuss recent advances in both mechanisms, w...
Source: Springer protocols feed by Pharmacology/Toxicology - January 27, 2014 Category: Drugs & Pharmacology Source Type: news
Discovery and Characterization of Leucine-Rich Repeat-Containing G Protein-Coupled Receptors
Leucine-rich repeat-containing G protein-coupled receptors (LGRs) are type A rhodopsin-like GPCRs that include the glycoprotein pituitary hormone receptors for the thyroid-stimulating, follicle-stimulating, and luteinizing hormones (TSH, FSH, and LH); a pair of receptors for insulin-like peptides (LGR7, LGR8); and the LGR4, LGR5, and LGR6 receptors, which are the basis of this chapter. LGRs were initially identified as conceptual proteins extracted from DNA sequence databases, displaying sequence similarity with the glycoprotein hormone receptors. In 2007, LGR5 was identified as a marker of adult stem cells in several tiss...
Source: Springer protocols feed by Pharmacology/Toxicology - January 27, 2014 Category: Drugs & Pharmacology Source Type: news
The Role of G-Protein-Coupled Receptors in Adult Neurogenesis
Adult neurogenesis is the process of creating new brain cells during adulthood. This involves several stages including proliferation, migration, differentiation, integration, and survival. G-protein-coupled receptors (GPCRs) regulate this process in both neurogenic regions of the brain: the subgranular and subventricular zones. The regulation of adult neurogenesis by GPCRs holds therapeutic promise for many neuropathologies. Several GPCRs activated by the neurotransmitters dopamine, glutamate, norepinephrine, and serotonin were shown to regulate adult neurogenesis. Melatonin, a neurohormone, and inflammatory molecules such...
Source: Springer protocols feed by Pharmacology/Toxicology - January 27, 2014 Category: Drugs & Pharmacology Source Type: news
Utilizing RNA-Seq to Define Phytochemical-Induced Alterations in Insulin and IGF-Regulated Transcriptomes
Cancer at its root is a genetic disease brought on by genomic alterations that lead to uncontrolled cell division, metastasis, and enhanced cell survival. The study of genomics can address many of the genetic abnormalities associated with cancer and represents a rapidly progressing field. Our knowledge base regarding specific gene mutations and alterations leading to cancer and the development of subsequent gene-targeted therapies is being rapidly transformed by the application of new RNA and DNA sequencing technology, including a number of high-throughput sequencing methods. In contrast to older Sanger sequencing methods,...
Source: Springer protocols feed by Pharmacology/Toxicology - November 27, 2013 Category: Drugs & Pharmacology Source Type: news
The Use of Seahorse Extracellular Flux Analyzer in Mechanistic Studies of Naturally Occurring Cancer Chemopreventive Agents
Metabolic pathways and bioenergetics were described in great detail over half a century ago, and during the past decade a resurgence in integrating these cellular processes with other biological properties of the cell, including growth control, protein kinase cascade signaling, cell cycle division, and autophagy, has occurred. Because many chronic pathological conditions, including cancer, are associated with altered metabolism and production of energy, developing new approaches to measure these cellular parameters is important. Recent studies also indicate that many naturally occurring cancer chemopreventive agents, such ...
Source: Springer protocols feed by Pharmacology/Toxicology - November 27, 2013 Category: Drugs & Pharmacology Source Type: news
The Azoxymethane Plus Dextran Sulfate Sodium-Induced Mouse Colon Cancer Model for the Study of Dietary Chemoprevention of Inflammation-Associated Carcinogenesis
The azoxymethane (AOM) plus dextran sulfate sodium (DSS)-induced mouse colon carcinogenesis model is a fascinating tool for investigating the pathogenesis and chemoprevention of colitis-associated colorectal cancer. In this two-stage mouse colon cancer model, tumorigenesis is initiated by a single intraperitoneal administration of the carcinogen AOM and promoted by DSS-induced inflammation. The successful induction of AOM plus DSS-induced colorectal cancer relies on several critical factors, such as the molecular weight and the dosage of DSS, the strain, age, and sex of animals, and other experimental conditions. Here, we ...
Source: Springer protocols feed by Pharmacology/Toxicology - November 27, 2013 Category: Drugs & Pharmacology Source Type: news
The Use of Mouse Models for Lung Cancer Chemoprevention Studies
Mouse lung tumor models are widely used in lung cancer chemopreventive studies. Lung cancer is a heterogeneous disease histologically classified as small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), which is usually divided into adenocarcinoma, squamous cell carcinoma (SCC), and large cell carcinoma. In order to illustrate the power of the mouse model in preclinical lung cancer investigations, comprehensive instructions for the selection of mice, genotyping, and induction of lung tumors (e.g., adenoma/adenocarcinoma, lung SCC, and SCLC) in mice are provided. We have described in detail the histolog...
Source: Springer protocols feed by Pharmacology/Toxicology - November 27, 2013 Category: Drugs & Pharmacology Source Type: news
