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α1 receptor blockade

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https://www.readbyqxmd.com/read/29426850/asymmetrical-ligand-induced-cross-regulation-of-chemokine-c-x-c-motif-receptor-4-by-%C3%AE-1-adrenergic-receptors-at-the-heteromeric-receptor-complex
#1
Xianlong Gao, Lauren J Albee, Brian F Volkman, Vadim Gaponenko, Matthias Majetschak
Recently, we reported that chemokine (C-X-C motif) receptor (CXCR)4 and atypical chemokine receptor 3 regulate α1-adrenergic receptors (α1-AR) through the formation of hetero-oligomeric complexes. Whether α1-ARs also regulate chemokine receptor function within such heteromeric receptor complexes is unknown. We observed that activation of α1b-AR within the α1b-AR:CXCR4 heteromeric complex leads to cross-recruitment of β-arrestin2 to CXCR4, which could not be inhibited with AMD3100. Activation of CXCR4 did not cross-recruit β-arrestin2 to α1b-AR...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29031714/dwarfism-and-insulin-resistance-in-male-offspring-caused-by-%C3%AE-1-adrenergic-antagonism-during-pregnancy
#2
Rebecca Oelkrug, Beate Herrmann, Cathleen Geissler, Lisbeth Harder, Christiane Koch, Hendrik Lehnert, Henrik Oster, Henriette Kirchner, Jens Mittag
OBJECTIVE: Maternal and environmental factors control the epigenetic fetal programming of the embryo, thereby defining the susceptibility for metabolic or endocrine disorders in the offspring. Pharmacological interventions required as a consequence of gestational problems, e.g. hypertension, can potentially interfere with correct fetal programming. As epigenetic alterations are usually only revealed later in life and not detected in studies focusing on early perinatal outcomes, little is known about the long-term epigenetic effects of gestational drug treatments...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28929924/the-search-for-a-subtype-selective-pet-imaging-agent-for-the-gabaa-receptor-complex-evaluation-of-the-radiotracer-11-c-ado-in-nonhuman-primates
#3
Shu-Fei Lin, Frederic Bois, Daniel Holden, Nabeel Nabulsi, Richard Pracitto, Hong Gao, Michael Kapinos, Jo-Ku Teng, Anupama Shirali, Jim Ropchan, Richard E Carson, Charles S Elmore, Neil Vasdev, Yiyun Huang
The myriad physiological functions of γ-amino butyric acid (GABA) are mediated by the GABA-benzodiazepine receptor complex comprising of the GABAA, GABAB, and GABAC groups. The various GABAA subunits with region-specific distributions in the brain subserve different functional and physiological roles. For example, the sedative and anticonvulsive effects of classical benzodiazepines are attributed to the α1 subunit, and the α2 and α3 subunits mediate the anxiolytic effect. To optimize pharmacotherapies with improved efficacy and devoid of undesirable side effects for the treatment of anxiety disorders, subtype-selective imaging radiotracers are required to assess target engagement at GABA sites and determine the dose-receptor occupancy relationships...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28882563/adenosine-a1-receptor-potentiated-glycinergic-transmission-in-spinal-cord-dorsal-horn-of-rats-after-peripheral-inflammation
#4
Hu-Hu Bai, Jiang-Ping Liu, Li Yang, Ji-Yuan Zhao, Zhan-Wei Suo, Xian Yang, Xiao-Dong Hu
Adenosine is present at the extracellular space within spinal cord dorsal horn and engaged in the processing of nociceptive sensory signals. Systemic or spinal administration of exogenous adenosine produces a potent analgesia against pathological pain. Here we found that inhibitory glycinergic neurotransmission was an important target for adenosine regulation. In spinal cord slices from intact rats, adenosine increased the inhibitory postsynaptic currents mediated by glycine receptors (GlyRs). In spinal slices from Complete Freund's Adjuvant-injected rats, adenosine potentiated glycinergic transmission to a more degree than in control rats...
September 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28635140/noradrenergic-signaling-in-the-vta-modulates-cocaine-craving
#5
Wojciech Barnaba Solecki, Klaudia Szklarczyk, Kamil Pradel, Krystyna Kwiatkowska, Grzegorz Dobrzański, Ryszard Przewłocki
Exposure to drug-associated cues evokes drug-seeking behavior and is regarded as a major cause of relapse. Conditional stimulus upregulates noradrenaline (NA) system activity, but the drug-seeking behavior depends particularly on phasic dopamine signaling downstream from the ventral tegmental area (VTA). The VTA dopamine-ergic activity is regulated via the signaling of alpha1 -adrenergic and alpha2 -adrenergic receptors (α1 -ARs and α2 -ARs); thus, the impact of the conditional stimulus on drug-seeking behavior might involve NAergic signaling in the VTA...
June 21, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28606743/alpha1-adrenergic-receptor-blockade-in-the-vta-modulates-fear-memories-and-stress-responses
#6
Wojciech B Solecki, Klaudia Szklarczyk, Adam Klasa, Kamil Pradel, Grzegorz Dobrzański, Ryszard Przewłocki
Activity of the ventral tegmental area (VTA) and its terminals has been implicated in the Pavlovian associative learning of both stressful and rewarding stimuli. However, the role of the VTA noradrenergic signaling in fear responses remains unclear. We aimed to examine how alpha1-adrenergic receptor (α1-AR) signaling in the VTA affects conditioned fear. The role of α1-AR was assessed using the micro-infusions into the VTA of the selective antagonists (0.1-1µg/0.5µl prazosin and 1µg/0.5µl terazosin) in acquisition and expression of fear memory...
August 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28492488/redistribution-of-cerebral-blood-flow-during-severe-hypovolemia-and-reperfusion-in-a-sheep-model-critical-role-of-%C3%AE-1-adrenergic-signaling
#7
René Schiffner, Sabine Juliane Bischoff, Thomas Lehmann, Florian Rakers, Sven Rupprecht, Juliane Reiche, Georg Matziolis, Harald Schubert, Matthias Schwab, Otmar Huber, Martin Schmidt
BACKGROUND: Maintenance of brain circulation during shock is sufficient to prevent subcortical injury but the cerebral cortex is not spared. This suggests area-specific regulation of cerebral blood flow (CBF) during hemorrhage. METHODS: Cortical and subcortical CBF were continuously measured during blood loss (≤50%) and subsequent reperfusion using laser Doppler flowmetry. Blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were also monitored...
May 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28455782/rpc4046-a-novel-anti-interleukin-13-antibody-blocks-il-13-binding-to-il-13-%C3%AE-1-and-%C3%AE-2-receptors-a-randomized-double-blind-placebo-controlled-dose-escalation-first-in-human-study
#8
Catherine S Tripp, Carolyn Cuff, Andrew L Campbell, Barbara A Hendrickson, Jeff Voss, Terry Melim, Chengbin Wu, Andrew D Cherniack, Kenneth Kim
INTRODUCTION: A unique anti-interleukin (IL)-13 monoclonal antibody, RPC4046, was generated on the basis of differential IL-13 receptor (R) blockade as assessed in a murine asthma model; the safety, tolerability, pharmacokinetics, and pharmacodynamics of RPC4046 were evaluated in a first-in-human study. METHODS: Anti-IL-13 antibodies with varying receptor blocking specificity were evaluated in the ovalbumin-induced murine asthma model. A randomized, double-blind, placebo-controlled, dose-escalation first-in-human study (NCT00986037) was conducted with RPC4046 in healthy adults and patients with mild to moderate controlled asthma...
June 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28392265/norepinephrine-regulates-cocaine-primed-reinstatement-via-%C3%AE-1-adrenergic-receptors-in-the-medial-prefrontal-cortex
#9
Karl T Schmidt, Jason P Schroeder, Stephanie L Foster, Katherine Squires, Brilee M Smith, Elizabeth G Pitts, Michael P Epstein, David Weinshenker
Drug-primed reinstatement of cocaine seeking in rats is thought to reflect relapse-like behavior and is mediated by the integration of signals from mesocorticolimbic dopaminergic projections and corticostriatal glutamatergic innervation. Cocaine-primed reinstatement can also be attenuated by systemic administration of dopamine β-hydroxylase (DBH) inhibitors, which prevent norepinephrine (NE) synthesis, or by α1-adrenergic receptor (α1AR) antagonists, indicating functional modulation by the noradrenergic system...
June 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28390894/methylene-blue-inhibits-gabaa-receptors-by-interaction-with-gaba-binding-site
#10
Zhenglan Chen, Ran Liu, Shao-Hua Yang, Glenn H Dillon, Renqi Huang
Methylene blue (MB) is commonly used in diagnostic procedures and is also used to treat various medical conditions. Neurological effects of MB have been reported in clinical observations and experimental studies. Thus the modulation of GABAA receptor function by MB was investigated. Whole-cell GABA-activated currents were recorded from HEK293 cells expressing various GABAA receptor subunit configurations. MB inhibition of GABA currents was apparent at 3 μM, and it had an IC50 of 31 μM in human α1β2γ2 receptors...
June 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28298638/pnaktide-attenuates-steatohepatitis-and-atherosclerosis-by-blocking-na-k-atpase-ros-amplification-in-c57bl6-and-apoe-knockout-mice-fed-a-western-diet
#11
Komal Sodhi, Krithika Srikanthan, Perrine Goguet-Rubio, Alexandra Nichols, Amrita Mallick, Athar Nawab, Rebecca Martin, Preeya T Shah, Muhammad Chaudhry, Saroj Sigdel, Mehiar El-Hamdani, Jiang Liu, Zijian Xie, Nader G Abraham, Joseph I Shapiro
We have previously reported that the α1 subunit of sodium potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a "western" diet containing high amounts of fat and fructose...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28294424/therapeutic-regulation-of-systemic-inflammation-in-xenograft-recipients
#12
Hayato Iwase, Hong Liu, Tao Li, Zhongquiang Zhang, Bingsi Gao, Hidetaka Hara, Martin Wijkstrom, Cassandra Long, Ryan Saari, David Ayares, David K C Cooper, Mohamed B Ezzelarab
Inflammation is known to preclude tolerance after transplantation. We have previously shown that systemic inflammation in xenograft recipients (SIXR) precedes activation of coagulation in the absence of T cell responses. Accordingly, SIXR may amplify innate and adaptive immune responses against xenografts after pig-to-primate xenotransplantation, even with efficient immunosuppressive therapy. We evaluated the impact of anti-inflammatory agents on pro-inflammatory cytokines and chemokines in pig artery patch and heart xenograft recipients...
March 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28212941/injections-of-the-of-the-%C3%AE-1-adrenoceptor-antagonist-prazosin-into-the-median-raphe-nucleus-increase-food-intake-and-fos-expression-in-orexin-neurons-of-free-feeding-rats
#13
Eduardo Simão da Silva, Rafael Appel Flores, Anderson Savaris Ribas, Ana Paula Taschetto, Moacir Serralvo Faria, Leandro Bueno Lima, Martin Metzger, José Donato, Marta Aparecida Paschoalini
Previously, we showed that the blockade of α1-adrenoreceptors in the median raphe nucleus (MnR) increased food intake in free-feeding rats, indicating that adrenergic mechanisms in the MnR participate in the regulation of food intake. However, the impact of such a pharmacological manipulation on other neural circuits related to food intake remains unknown. In the current study, we sought to identify forebrain regions which are responsive to α1-adrenergic receptor blockade and presumably involved in the modulation of the feeding response...
May 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28199786/alpha-adrenergic-receptor-blockade-increases-capillarization-and-fractional-o2-extraction-and-lowers-blood-flow-in-contracting-human-skeletal-muscle
#14
S P Mortensen, S Egginton, M Madsen, J B Hansen, G D W Munch, U W Iepsen, T Åkerström, B K Pedersen, Y Hellsten
AIM: To assess the effect of elevated basal shear stress on angiogenesis in humans and the role of enhanced skeletal muscle capillarization on blood flow and O2 extraction. METHODS: Limb haemodynamics and O2 extraction were measured at rest and during one-leg knee-extensor exercise (12 and 24 W) in 10 healthy untrained young men before and after 4-week treatment with an α1 receptor-antagonist (Terazosin, 1-2 mg day(-1) ). Corresponding biopsies were taken from the m...
September 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28029729/combined-treatment-with-dipeptidyl-peptidase-4-inhibitor-sitagliptin-and-angiotensin-ii-type-1-receptor-blocker-losartan-suppresses-progression-in-a-non-diabetic-rat-model-of-steatohepatitis
#15
Yasushi Okura, Tadashi Namisaki, Kei Moriya, Mitsuteru Kitade, Kosuke Takeda, Kosuke Kaji, Ryuichi Noguchi, Norihisa Nishimura, Kenichiro Seki, Hideto Kawaratani, Hiroaki Takaya, Shinya Sato, Yasuhiko Sawada, Naotaka Shimozato, Masanori Furukawa, Keisuke Nakanishi, Soichiro Saikawa, Takuya Kubo, Kiyoshi Asada, Hitoshi Yoshiji
AIM: Dipeptidyl peptidase-4 (DPP4) inhibitors (DPP4-I) are oral glucose-lowering drugs for type 2 diabetes mellitus. Previously, we reported that DPP4-I (sitagliptin) exerted suppressive effects on experimental liver fibrosis in rats. Blockade of the renin-angiotensin system by angiotensin-II type 1 receptor blocker (losartan), commonly used in the management of hypertension, has been shown to significantly alleviate hepatic fibrogenesis and carcinogenesis. We aimed to elucidate the effects and possible mechanisms of a sitagliptin + losartan combination on the progression of non-diabetic non-alcoholic steatohepatitis (NASH) in a rat model...
November 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27812496/reversible-exacerbation-of-obstructive-sleep-apnea-by-%C3%AE-1-adrenergic-blockade-with-tamsulosin-a-case-report
#16
Mark Moran
Obstructive sleep apnea (OSA) is characterized by repeated involuntary closure of the pharyngeal airspace during sleep. Normal activity of the genioglossus (GG) muscle is important in maintaining airway patency, and inhibition of GG activity can contribute to airway closure. Neurons in the hypoglossal motor nucleus (HMN) regulate GG activity. Adrenergic tone is an important regulator of HMN neuronal excitability. In laboratory models α1-adrenergic antagonists inhibit HMN neurons and GG activity, suggesting that α1-adrenergic antagonism might adversely affect patients with OSA...
2016: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/27769919/preoperative-levels-of-catecholamines-and-metanephrines-and-intraoperative-hemodynamics-of-patients-undergoing-pheochromocytoma-and-paraganglioma-resection
#17
Toby N Weingarten, Tasha L Welch, Tamara L Moore, Gulshat F Walters, Joni L Whipple, Alexandre Cavalcante, Irina Bancos, William F Young, Lucinda M Gruber, Muhammad Z Shah, Travis J McKenzie, Darrell R Schroeder, Juraj Sprung
OBJECTIVE: To determine whether, despite pharmacologic adrenergic receptor blockade, higher preoperative levels of catecholamines and metanephrines (adrenergic activity) are associated with increased intraoperative complications. MATERIALS AND METHODS: Records of patients undergoing paraganglioma and pheochromocytoma (PGL-PCC) resection from January 1, 2000, to June 30, 2015, were reviewed for preoperative levels of adrenergic activity, intraoperative variability in blood pressure and heart rate (range), and postoperative outcomes (hypotension requiring treatment)...
February 2017: Urology
https://www.readbyqxmd.com/read/27754015/br-04-1management-of-treatment-resistant-hypertension
#18
David John Webb
Treatment-resistant hypertension (TRH) is defined as the failure to achieve an office BP target of <140/90 mmHg (<130/80 mmHg in patients with chronic kidney disease (CKD) or diabetes) in patients with hypertension (HT), despite adherence to at least 3 antihypertensive medications at optimal tolerated doses, ideally including a diuretic (Calhoun et al., Circulation 2008). TRH identifies patients with hard-to-treat HT, who might benefit from specialist investigation and treatment. Although some studies put the prevalence of TRH as >10%, these levels may be inflated by white-coat hypertension and poor adherence...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27702852/antiadrenergic-autoimmunity-in-postural-tachycardia-syndrome
#19
Artur Fedorowski, Hongliang Li, Xichun Yu, Kristi A Koelsch, Valerie M Harris, Campbell Liles, Taylor A Murphy, Syed M S Quadri, Robert Hal Scofield, Richard Sutton, Olle Melander, David C Kem
Aims: Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR). Methods and results: Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro...
July 1, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/27228963/dynamic-cerebral-autoregulation-is-unrelated-to-decrease-in-external-carotid-artery-blood-flow-during-acute-hypotension-in-healthy-young-men
#20
Shigehiko Ogoh, Henrik Sørensen, Ai Hirasawa, Hiroyuki Sasaki, Takuro Washio, Takeshi Hashimoto, Damian M Bailey, Niels H Secher
What is the central question of this study? Dynamic cerebral autoregulation (CA) is impaired by sympathetic blockade, and the external carotid artery (ECA) vascular bed may prevent adequate internal carotid artery blood flow. We examined whether α1 -receptor blockade-induced attenuation of dynamic CA is related to reduced ECA vasoconstriction. What is the main finding and its importance? α1 -Receptor blockade attenuated dynamic CA, but in contrast to our hypothesis did not affect the ECA blood flow response to acute hypotension...
August 1, 2016: Experimental Physiology
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