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https://www.readbyqxmd.com/read/28446017/dexmedetomidine-oral-mucosa-patch-for-sedation-suppresses-apoptosis-in-hippocampus-of-normal-rats
#1
Je Hoon Park, Il Gyu Ko, Sung Eun Kim, Jun Jang Jin, Lakkyong Hwang, Chang Ju Kim, Soo Hwan Yoon, Jongki Hong, Jun Young Chung, Deok Won Lee
PURPOSE: Dexmedetomidine, an α2-adrenergic agonist, provides sedative and analgesic effects without significant respiratory depression. Dexmedetomidine has been suggested to have an antiapoptotic effect in response to various brain insults. We developed an oral mucosa patch using dexmedetomidine for sedation. The effects of the dexmedetomidine oral mucosa patch on cell proliferation and apoptosis in the hippocampus were evaluated. METHODS: A hydrogel oral mucosa patch was adhered onto the oral cavity of physiologically normal rats, and was attached for 2 hours, 6 hours, 12 hours, or 24 hours...
April 2017: International Neurourology Journal
https://www.readbyqxmd.com/read/28444807/rkip-lessons-of-a-better-way-for-%C3%AE-adrenergic-receptor-activation-in-the-heart
#2
Kristina Lorenz, Marsha Rich Rosner, Theresa Brand, Joachim P Schmitt
Stimulation of β-adrenergic receptors (βAR) provides the most efficient physiological mechanism to enhance contraction and relaxation of the heart. Activation of βAR allows rapid enhancement of myocardial function in order to fuel the muscles for running and fighting in a fight-or-flight response. Likewise, βAR get activated during cardiovascular disease in an attempt to counteract the restrictions of cardiac output. However, long-term stimulation of βAR increases the likelihood of cardiac arrhythmias, adverse ventricular remodelling, decline of cardiac performance and premature death, thereby limiting the use of βAR agonists in the treatment of heart failure...
April 26, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28444738/factors-influencing-biased-agonism-in-recombinant-cells-expressing-the-human-%C3%AE-1a-adrenoceptor
#3
Edilson Dantas da Silva Junior, Masaaki Sato, Jon Merlin, Natalie Broxton, Dana S Hutchinson, Sabatino Ventura, Bronwyn A Evans, Roger J Summers
BACKGROUND AND PURPOSE: Agonists acting at G protein-coupled receptors promote biased signalling via Gα or Gβγ subunits, G protein-coupled receptor kinases and β-arrestins. Since demonstration of biased agonism has implications for drug discovery, it is essential to consider confounding factors contributing to bias. We have examined bias at human α1A -adrenoceptors stably expressed at low levels in CHO-K1 cells, identifying off-target effects at endogenous receptors that contribute to ERK1/2 phosphorylation in response to the agonist oxymetazoline...
April 25, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28443535/effects-of-immunocastration-and-%C3%AE-adrenergic-agonists-on-the-performance-and-carcass-traits-of-feedlot-finished-nellore-cattle
#4
D S Antonelo, M R Mazon, K E Z Nubiato, J F M Gómez, D J Brigida, R C Gomes, A S Netto, P R Leme, S L Silva
β-Adrenergic agonists (β-AA) are non-hormonal growth promoters which promote muscle hypertrophy in supplemented animals. The effects of two β-AA in combination with the immunocastration technique on the performance and carcass traits were evaluated using 96 feedlot Nellore males in a randomized complete block design with two sex conditions (immunocastrated (IC) v. non-castrated (NC)) and three treatments: CON (no β-agonists added), RH (300 mg of ractopamine hydrochloride/day, for 33 days) or ZH (80 mg of zilpaterol·hydrochloride animal/day for 30 days, removed 3 days for required withdrawal period)...
April 26, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28442626/active-life-active-antitumor-defense
#5
Leslie K Ferrarelli
An active lifestyle in mice stimulates adrenergic signaling in the nervous system that enhances the function of antitumor natural killer cells.
April 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28442571/beta-2-adrenergic-receptor-activation-mobilizes-intracellular-calcium-via-a-non-canonical-camp-independent-signaling-pathway
#6
Monica Galaz-Montoya, Sara J Wright, Gustavo J Rodriguez, Olivier Lichtarge, Theodore G Wensel
Beta adrenergic receptors (βARs) are G protein-coupled receptors essential for physiological responses to the hormones/neurotransmitters epinephrine and norepinephrine which are found in the nervous system and throughout the body. They are the targets of numerous widely used drugs, especially in the case of the most extensively studied βAR, β2AR, whose ligands are used for asthma and cardiovascular disease. βARs signal through Gαs G proteins and via activation of adenylyl cyclase and cAMP-dependent protein kinase, but some alternative downstream pathways have also been proposed, which could be important for understanding normal physiological functioning of β2AR signaling and its disruption in disease...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28441717/dexmedetomidine-relieves-formaldehyde-induced-pain-in-rats-through-both-%C3%AE-2-adrenoceptor-and-imidazoline-receptor
#7
Hong Zhang, Xiang Yan, De-Gui Wang, Yu-Fang Leng, Zhan-Hai Wan, Yong-Qiang Liu, Yan Zhang
Dexmedetomidine (DEX) is a highly selective α2 adrenergic receptor agonist. In this study, we investigated the analgesic effect and the underlying mechanisms of DEX on inflammatory visceral pain in rats. Twenty-five male Sprague Dawley (SD) rats were randomly divided into 5 groups, including control, sham, low dose DEX, medium dose DEX and high dose DEX group. Pain was induced with 10% formalin and scored every 15min till 2 h-post the induction. Hematoxylin-eosin (HE) staining was used to evaluate the toxicity of DEX on spinal cord neurons...
April 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28440910/subacute-pyridostigmine-exposure-increases-heart-rate-recovery-and-cardiac-parasympathetic-tone-in-rats
#8
Manushree Bharadwaj, Carey Pope, Michael Davis, Stuart Katz, Christian Cook, Lara Maxwell
Heart rate recovery (HRR) describes the rapid deceleration of heart rate after strenuous exercise and is an indicator of parasympathetic tone. A reduction in parasympathetic tone occurs in patients with congestive heart failure, resulting in prolonged HRR. Acetylcholinesterase inhibitors, such as pyridostigmine, can enhance parasympathetic tone by increasing cholinergic input to the heart. The objective of this study was to develop a rodent model of HRR to test the hypothesis that subacute pyridostigmine administration decreases cholinesterase activity and accelerates HRR in rats...
April 25, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28440455/%C3%AE-adrenoceptor-mediated-enhanced-inducibility-of-atrial-fibrillation-in-a-canine-system-inflammation-model
#9
Ying-Ying Chen, Ze-Wei Sun, Jian-Ping Jiang, Xiao-Dong Kang, Lin-Lin Wang, Yue-Liang Shen, Xu-Dong Xie, Liang-Rong Zheng
The exact mechanism associated with inflammation and atrial fibrillation (AF) remains unknown. The aim of the present study was to investigate the roles of connexin 43 (Cx43) and a1‑adrenergic receptor (α1‑AR) activation in the pathogenesis of system inflammation‑induced AF. A canine model of chronic low‑grade system inflammation was established by administrating a low dose of lipopolysaccharide (LPS; 0.1 µg/kg) for 2 weeks. Programmed stimulation was applied on the right atrial appendage to determine the effective refractory periods (ERP) and the window of vulnerability (WOV)...
April 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440105/effect-of-doxazosin-on-stress-reactivity-and-the-ability-to-resist-smoking
#10
Terril L Verplaetse, Andrea H Weinberger, Lindsay M Oberleitner, Kathryn Mz Smith, Brian P Pittman, Julia M Shi, Jeanette M Tetrault, Meaghan E Lavery, Marina R Picciotto, Sherry A McKee
Preclinical findings support a role for α1-adrenergic antagonists in reducing nicotine-motivated behaviors, but these findings have yet to be translated to humans. The current study evaluated whether doxazosin would attenuate stress-precipitated smoking in the human laboratory. Using a well-validated laboratory analogue of smoking-lapse behavior, this pilot study evaluated whether doxazosin (4 and 8 mg/day) versus placebo attenuated the effect of stress (vs neutral imagery) on tobacco craving, the ability to resist smoking and subsequent ad-libitum smoking in nicotine-deprived smokers ( n=35)...
April 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28439935/neonatal-immune-challenge-followed-by-adult-immune-challenge-induces-epigenetic-susceptibility-to-aggravated-visceral-hypersensitivity
#11
J E Aguirre, J H Winston, S K Sarna
BACKGROUND: Abdominal pain is one of the major symptoms of inflammatory Bowel Disease (IBD). The inflammatory mediators released by colon inflammation are known to sensitize the afferent neurons, which is one of the contributors to abdominal pain. However, not all IBD patients have abdominal pain, and some patients report abdominal pain during remission, suggesting contributions of other pathological factors to abdominal pain in IBD. Epidemiological studies found early-life gastrointestinal infections a risk factor for IBD symptoms and adult-life gastrointestinal infections may trigger the onset of IBD...
April 25, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28439254/distinct-conformational-dynamics-of-three-g-protein-coupled-receptors-measured-using-flash-bret-biosensors
#12
Kyla Bourque, Darlaine Pétrin, Rory Sleno, Dominic Devost, Alice Zhang, Terence E Hébert
A number of studies have profiled G protein-coupled receptor (GPCR) conformation using fluorescent biaresenical hairpin binders (FlAsH) as acceptors for BRET or FRET. These conformation-sensitive biosensors allow reporting of movements occurring on the intracellular surface of a receptor to investigate mechanisms of receptor activation and function. Here, we generated eight FlAsH-BRET-based biosensors within the sequence of the β2-adrenergic receptor (β2AR) and compared agonist-induced responses to the angiotensin II receptor type I (AT1R) and the prostaglandin F2α receptor (FP)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28438833/g-protein-gi1-exhibits-basal-coupling-but-not-preassembly-with-g-protein-coupled-receptors
#13
Alexey Bondar, Josef Lazar
The Gi/o protein family transduces signals from a diverse group of G protein-coupled receptors (GPCRs). The observed specificity of Gi/o-GPCR coupling and high rate of Gi/o signal transduction have been hypothesized to be enabled by existence of stable associates between Gi/o proteins and their cognate GPCRs in the inactive state (Gi/o-GPCR preassembly). To test this hypothesis, we applied the recently developed technique of two-photon polarization microscopy (2PPM) to Gαi1 subunits labeled with fluorescent proteins and four GPCRs (the α2A-adrenergic receptor (α2A-AR), γ-aminobutyric acid receptor B (GABAB), cannabinoid receptor type 1 (CB1R) and dopamine receptor type 2 (D2R))...
April 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28438566/t-type-voltage-gated-calcium-channels-are-involved-in-endothelium-dependent-relaxation-of-mice-pulmonary-artery
#14
Guillaume Gilbert, Arnaud Courtois, Mathilde Dubois, Laure-Anne Cussac, Thomas Ducret, Philippe Lory, Roger Marthan, Jean-Pierre Savineau, Jean-François Quignard
In pulmonary arterial endothelial cells, Ca(2+) channels and intracellular Ca(2+)concentration ([Ca(2+)]i) control the release of vasorelaxant factors such as nitric oxide and are involved in the regulation of pulmonary arterial blood pressure. The present study was undertaken to investigate the implication of T-type voltage-gated Ca(2+)channels (T-VGCCs, Cav3.1 channel) in the endothelium-dependent relaxation of intrapulmonary arteries. Relaxation was quantified by means of a myograph in wild type and Cav3...
April 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28438532/kinetic-properties-and-adrenergic-control-of-trek-2-like-channels-in-rat-medial-prefrontal-cortex-mpfc-pyramidal-neurons
#15
W Ładno, M Gawlak, P Szulczyk, E Nurowska
TREK-2-like channels were identified on the basis of electrophysiological and pharmacological tests performed on freshly isolated and enzymatically/mechanically dispersed pyramidal neurons of the rat medial prefrontal cortex (mPFC). Single-channel currents were recorded in cell-attached configuration and the impact of adrenergic receptors (α1, α2, β) stimulation on spontaneously appearing TREK-2-like channel activity was tested. The obtained results indicate that noradrenaline decreases the mean open probability of TREK-2-like channel currents by activation of β1 but not of α1- and α2-adrenergic receptors...
April 21, 2017: Brain Research
https://www.readbyqxmd.com/read/28437032/autonomic-receptor-mediated-regulation-of-production-and-release-of-nitric-oxide-in-normal-and-malignant-human-urothelial-cells
#16
Michael Winder, Renata Vesela, Patrik Aronsson, Bhavik Patel, Thomas Carlsson
In the urinary bladder, the main source of NO seems to be the urothelium and the underlying suburothelium. In this study, we aimed to characterize how receptors in the human urothelium regulate the production and release of NO. For this, we cultured two human urothelial cell lines - the normal immortalized cell line UROtsa and the malignant cell line T24. These were treated with an array of agonists and antagonists with affinity for adrenergic, muscarinic and purinergic receptors. The production of NO and expression of nitric oxide synthase (NOS) was studied by immunocytochemistry and western blotting...
April 24, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28436486/muscle-wasting-and-cachexia-in-heart-failure-mechanisms-and-therapies
#17
REVIEW
Stephan von Haehling, Nicole Ebner, Marcelo R Dos Santos, Jochen Springer, Stefan D Anker
Body wasting is a serious complication that affects a large proportion of patients with heart failure. Muscle wasting, also known as sarcopenia, is the loss of muscle mass and strength, whereas cachexia describes loss of weight. After reaching guideline-recommended doses of heart failure therapies, the most promising approach to treating body wasting seems to be combined therapy that includes exercise, nutritional counselling, and drug treatment. Nutritional considerations include avoiding excessive salt and fluid intake, and replenishment of deficiencies in trace elements...
April 24, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28435771/brown-adipose-tissue-bioenergetics-a-new-methodological-approach
#18
María Calderon-Dominguez, Martín Alcalá, David Sebastián, Antonio Zorzano, Marta Viana, Dolors Serra, Laura Herrero
The rediscovery of brown adipose tissue (BAT) in humans and its capacity to oxidize fat and dissipate energy as heat has put the spotlight on its potential as a therapeutic target in the treatment of several metabolic conditions including obesity and diabetes. To date the measurement of bioenergetics parameters has required the use of cultured cells or extracted mitochondria with the corresponding loss of information in the tissue context. Herein, we present a method to quantify mitochondrial bioenergetics directly in BAT...
April 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28434969/translational-science-approach-for-assessment-of-cardiovascular-effects-and-proarrhythmogenic-potential-of-the-beta-3-adrenergic-agonist-mirabegron
#19
Cees Korstanje, Masanori Suzuki, Koichiro Yuno, Shuichi Sato, Masashi Ukai, Marlowe J Schneidkraut, Gan X Yan
INTRODUCTION: Translational assessment of cardiac safety parameters is a challenge in clinical development of beta-3 adrenoceptor agonists. The preclinical tools are presented that were used for assessing human safety for mirabegron. METHODS: Studies were performed on electrical conductance at ion channels responsible for cardiac repolarization (IKr, IKs, Ito, INa, and ICa,L), on QT-interval, subendocardial APD90, Tpeak-end interval, and arrhythmia's in ventricular dog wedge tissue in vitro and on cardiovascular function (BP, HR, and QTc) in conscious dogs...
April 20, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28433253/neuropeptide-s-increases-motor-activity-and-thermogenesis-in-the-rat-through-sympathetic-activation
#20
Takuya Ensho, Keiko Nakahara, Yoshihiro Suzuki, Noboru Murakami
The central role of neuropeptide S (NPS), identified as the endogenous ligand for GPR154, now named neuropeptide S receptor (NPSR), has not yet been fully clarified. We examined the central role of NPS for body temperature, energy expenditure, locomotor activity and adrenal hormone secretion in rats. Intracerebroventricular (icv) injection of NPS increased body temperature in a dose-dependent manner. Energy consumption and locomotor activity were also significantly increased by icv injection of NPS. In addition, icv injection of NPS increased the peripheral blood concentration of adrenalin and corticosterone...
April 13, 2017: Neuropeptides
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