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https://www.readbyqxmd.com/read/28643105/differential-role-of-gabaa-receptors-and-neuroligin-2-for-perisomatic-gabaergic-synapse-formation-in-the-hippocampus
#1
Patrizia Panzanelli, Simon Früh, Jean-Marc Fritschy
Perisomatic GABAergic synapses onto hippocampal pyramidal cells arise from two populations of basket cells with different neurochemical and functional properties. The presence of the dystrophin-glycoprotein complex in their postsynaptic density (PSD) distinguishes perisomatic synapses from GABAergic synapses on dendrites and the axon-initial segment. Targeted deletion of neuroligin 2 (NL2), a transmembrane protein interacting with presynaptic neurexin, has been reported to disrupt postsynaptic clustering of GABAA receptors (GABAAR) and their anchoring protein, gephyrin, at perisomatic synapses...
June 22, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28638920/-a-study-on-toxic-effects-of-sodium-salicylate-on-rat-cochlear-spiral-ganglion-neurons-dopamine-receptors-mediate-expressions-of-nmda-and-gabaa-receptors
#2
Ting-Jia Wei, Hui-Ying Chen, Xi Huang, Jing-Jin Weng, Jiang-Yuan Qin, Ji-Ping Su
The aim of the present study was to observe whether dopamine receptor (DR) was involved in the effects of sodium salicylate (SS) on the expressions of N-methyl-D-aspartic acid (NMDA) and γ-aminobutyric acid (GABA) receptors in rat cochlear spiral ganglion neurons (SGNs). Forty-eight hours after primary culture of rat SGNs, immunofluorescence technique was applied to detect expressions of DR1 and DR2, the two subtypes of dopamine receptors. Western blot was performed to assess NMDA receptor NR1 subunit and GABAA receptor subunit α2 (GABRα2) protein expressions in the SGNs after the treatments of SS alone or in combination with DR antagonists...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28638085/differential-regulations-of-vestibulo-ocular-reflex-and-optokinetic-response-by-%C3%AE-and-%C3%AE-2-adrenergic-receptors-in-the-cerebellar-flocculus
#3
Ryo Wakita, Soshi Tanabe, Kazunari Tabei, Asako Funaki, Takuma Inoshita, Tomoo Hirano
Norepinephrine modulates synaptic plasticity in various brain regions and is implicated in memory formation, consolidation and retrieval. The cerebellum is involved in motor learning, and adaptations of the vestibulo-ocular reflex (VOR) and optokinetic response (OKR) have been studied as models of cerebellum-dependent motor learning. Previous studies showed the involvement of adrenergic systems in the regulation of VOR, OKR and cerebellar synaptic functions. Here, we show differential contributions of β- and α2-adrenergic receptors in the mouse cerebellar flocculus to VOR and OKR control...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28636360/proneurogenic-effects-of-trazodone-in-murine-and-human-neural-progenitors
#4
Valeria Bortolotto, Francesca Mancini, Giorgina Mangano, Rita Salem, Er Xia, Erika Del Grosso, Michele Bianchi, Pier Luigi Canonico, Lorenzo Polenzani, Mariagrazia Grilli
Several antidepressants increase adult hippocampal Neurogenesis (ahNG) in rodents, primates and, potentially, in humans. This effect may at least partially account for their therapeutic activity. The availability of antidepressants whose mechanism of action involves different neurotransmitter receptors represents an opportunity for increasing our knowledge on their distinctive peculiarities and for dissecting the contribution of receptor subtypes in ahNG modulation. The aim of this study was to evaluate, in vitro, the effects of the antidepressant trazodone (TZD) on ahNG by using primary cultures of adult hippocampal Neural Progenitor Cells (ahNPC) and human iPSC-derived NPC...
June 21, 2017: ACS Chemical Neuroscience
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/28633926/synergic-stimulation-of-serotonin-5-ht1a-receptor-and-%C3%AE-2-adrenoceptors-for-neuropathic-pain-relief-preclinical-effects-of-2-substituted-imidazoline-derivatives
#6
Lorenzo Di Cesare Mannelli, Carla Ghelardini, Laura Micheli, Fabio Del Bello, Mario Giannella, Alessandro Piergentili, Wilma Quaglia
Neuropathic pain affects millions of people causing disability and impairing quality of life. Commonly used analgesics are generally characterized by limited therapeutic outcomes. The serotonin 5-HT1A receptor and the α2 adrenergic receptors are involved in central nociceptive mechanisms with a pivotal role in the inhibitory descending pain pathway. Since their stimulation may modulate the nervous signaling altered by neuropathies, the purpose of the present research is the study of the combined activation of 5-HT1A and α2 receptors by rationally designed imidazoline ligands ((S)-1 and 2-5) in a rat model of neuropathic pain (chronic constriction injury - CCI)...
June 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28630263/determination-of-the-residues-in-the-extracellular-domain-of-the-nicotinic-%C3%AE-subunit-required-for-the-actions-of-physostigmine-on-neuronal-nicotinic-receptors
#7
Xiaochun Jin, Allison L Germann, Daniel J Shin, Gustav Akk, Joseph H Steinbach
Physostigmine can potentiate and inhibit neuronal nicotinic receptors, in addition to inhibiting the activity of acetylcholinesterase. We found that receptors containing 3 copies of the α2 subunit are inhibited by low concentrations of physostigmine in contrast to receptors containing 3 copies of the α4 subunit that are potentiated. We exploited this observation to determine regions required for the actions of physostigmine. Chimeric constructs of the α2 and α4 subunits located two regions in the extracellular amino-terminal domain of the subunit: the E loop (a loop of the transmitter-binding domain) and a region closer to the amino-terminus that collectively could completely determine the different effects of physostigmine...
June 19, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28628756/atypical-sympathomimetic-drug-lerimazoline-mediates-contractile-effects-in-rat-aorta-predominantly-by-5-ht2a-receptors
#8
Eldina Rizvić, Goran Janković, Slađana Kostić-Rajačić, Miroslav M Savić
Lerimazoline is a sympathomimetic drug that belongs to the imidazoline class of compounds, and is used as a nasal decongestant. Studies on lerimazoline are rare, and its pharmacological profile is not completely understood. Here, we analyzed the affinity of lerimazoline for dopamine receptor D2, serotonin 5-HT1A and 5-HT2A receptors and α1-adrenoceptor, and investigated lerimazoline contractile effects in isolated rat thoracic aorta. We also determined the effect of several antagonists on the contractile response to lerimazoline, including prazosin (α1-adrenoceptor antagonist), RX 821002 and rauwolscine (α2-adrenoceptor antagonists), JP 1302 (α2C-adrenoceptor antagonist), methiothepin (non-selective 5-HT receptor antagonist), SB 224289 (5-HT1B receptor antagonist), BRL 15572 (5-HT1D receptor antagonist), and ketanserin (5-HT2A receptor antagonist)...
June 19, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28626012/pharmacological-modulation-of-noradrenergic-arousal-circuitry-disrupts-functional-connectivity-of-the-locus-coeruleus-in-humans
#9
Andrew H Song, Aaron Kucyi, Vitaly Napadow, Emery N Brown, Marco L Loggia, Oluwaseun Akeju
State dependent activity of locus coeruleus (LC) neurons has long suggested a role for noradrenergic modulation of arousal. However, in vivo insights into noradrenergic arousal circuitry have been constrained by the fundamental inaccessibility of the human brain for invasive studies. Functional magnetic resonance imaging (fMRI) studies performed during site-specific pharmacological manipulations of arousal levels may be used to study brain arousal circuitry. Dexmedetomidine is an anesthetic that alters the level of arousal by selectively targeting α2 adrenergic receptors on LC neurons, resulting in reduced firing rate and norepinephrine release...
June 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28623711/contribution-of-dopaminergic-and-noradrenergic-systems-in-the-antinociceptive-effect-of-%C3%AE-phenylalanyl-acetophenone
#10
Fernanda S S Sousa, Roberta G Anversa, Paloma T Birmann, Maurice N de Souza, Renata Balaguez, Diego Alves, Cristiane Luchese, Ethel A Wilhelm, Lucielli Savegnago
BACKGROUND: This study evaluated the antinociceptive action of α-(phenylalanyl) acetophenone (PSAP) in mice. METHODS: Evaluated whether the serotonergic, adrenergic and dopaminergic systems are involved in PSAP antinociceptive activity. PSAP was administered intragastrically (ig) 30min prior to formalin or glutamate test and compared with a standard drug, meloxicam (10mg/kg, ig). RESULTS: The treatment with PSAP (10-50mg/kg) caused inhibition in the neurogenic phase and reduced the paw oedema caused by intraplantar (ipl) injection of formalin...
March 27, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28622977/evolution-of-the-%C3%AE-2-adrenoreceptors-in-vertebrates-adra2d-is-absent-in-mammals-and-crocodiles
#11
Héctor A Céspedes, Kattina Zavala, Michael W Vandewege, Juan C Opazo
Evolutionary studies of genes that have been functionally characterized and whose variation has been associated with pathological conditions represent an opportunity to understand the genetic basis of pathologies. α2-Adrenoreceptors (ADRA2) are a class of G protein-coupled receptors that regulate several physiological processes including blood pressure, platelet aggregation, insulin secretion, lipolysis, and neurotransmitter release. This gene family has been extensively studied from a molecular/physiological perspective, yet much less is known about its evolutionary history...
June 13, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28621257/oral-transmucosal-detomidine-gel-in-new-zealand-white-rabbits-oryctolagus-cuniculus
#12
Morika D Williams, C Tyler Long, Jessica R Durrant, Gabriel P McKeon, Heather R Shive, Emily H Griffith, Kristen M Messenger, Richard E Fish
Handling and restraining rabbits for routine procedures may be impossible without prior sedation, result in unnecessarystress or injury to the rabbit or handler, and increase experimental variability. Parenteral administration of sedatives can cause stress also, as well as localized pain and tissue damage, especially in fractious animals. Detomidine hydrochloride, an α2-adrenergic receptor agonist, is commercially available in an oral transmucosal (OTM) gel formulation that is FDA-approved for sedation and restraint in horses...
June 15, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28613003/systematic-review-pharmacotherapy-for-high-output-enterostomies-or-enteral-fistulas
#13
REVIEW
F E E de Vries, L F Reeskamp, O van Ruler, I van Arum, W Kuin, G Dijksta, J W Haveman, M A Boermeester, M J Serlie
BACKGROUND: High-output enterocutaneous fistula or enterostomies can cause intestinal failure. There is a wide variety of options in medical management of patients with high output. AIM: To systematically review the literature on available pharmacotherapy to reduce output and to propose an algorithm for standard of care. METHODS: Relevant databases were systematically reviewed to identify studies on pharmacotherapy for reduction in (high-) output enterostomies or fistula...
June 14, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28612843/tricellulin-is-regulated-via-interleukin-13-receptor-%C3%AE-2-affects-macromolecule-uptake-and-is-decreased-in-ulcerative-colitis
#14
S M Krug, C Bojarski, A Fromm, I M Lee, P Dames, J F Richter, J R Turner, M Fromm, J-D Schulzke
In the two inflammatory bowel diseases, ulcerative colitis (UC) and Crohn's disease (CD), altered expression of tight junction (TJ) proteins leads to an impaired epithelial barrier including increased uptake of luminal antigens supporting the inflammation. Here, we focused on regulation of tricellulin (Tric), a protein of the tricellular TJ essential for the barrier against macromolecules, and hypothesized a role in paracellular antigen uptake. We report that Tric is downregulated in UC, but not in CD, and that its reduction increases the passage of macromolecules...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28611548/hippocampal-characteristics-and-invariant-sequence-elements-distribution-of-glra2-and-glra3-c-to-u-editing
#15
Philipp Schaefermeier, Sarah Heinze
Glycine receptor α2 and α3 subunit (GLRA2/GLRA3) high-affinity variants, of which the subjacent amino acid substitutions issue from C-to-U RNA editing, are thought to influence tonic inhibition and pathophysiology. In light of the detection of GLRA3 NM_006529:r.1157C>U and GLRA2 NM_002063:r.1416C>U exchanges in hippocampus explants of temporal lobe epilepsy patients, we now examine the healthy situation and relate it to the epileptic situation by ascertaining controls in a legitimate reanalysis. The GLRA2 and GLRA3 editing events that would ultimately result in a glycine receptor with increased affinity occur in the postmortem nonepileptic hippocampus...
March 2017: Molecular Syndromology
https://www.readbyqxmd.com/read/28594540/noradrenergic-modulation-of-dopamine-transmission-evoked-by-electrical-stimulation-of-the-locus-coeruleus-in-the-rat-brain
#16
Jin W Park, Rohan V Bhimani, Jinwoo Park
Central norepinephrine (NE) and dopamine (DA) are involved in a variety of physiological functions and behaviors. Accumulating evidence suggests that NE neurons originating from the locus coeruleus (LC) innervate DA neurons of the ventral tegmental area (VTA) and influence VTA-DA neural activity. However, the underlying mechanisms of how LC-NE regulates DA transmission via VTA-DA neurons remain largely unexplored. Herein, we investigated how electrical stimulation of the LC modulates VTA-DA neurotransmission in the nucleus accumbens (NAc)...
June 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28589556/characterization-of-functional-%C3%AE-opioid-receptor-turnover-in-rat-locus-coeruleus-an-electrophysiological-and-immunocytochemical-study
#17
María Carmen Medrano, María Teresa Santamarta, Patricia Pablos, Zigor Aira, Itsaso Buesa, Jon Jatsu Azkue, Aitziber Mendiguren, Joseba Pineda
BACKGROUND AND PURPOSE: Regulation of μ receptor (MOR) dynamics such as MOR trafficking is a possible mechanism underlying opioid tolerance that contributes to inefficient recycling of opioid responses. We aimed to characterize the functional MOR turnover in the noradrenergic nucleus locus coeruleus (LC). EXPERIMENTAL APPROACH: We measured opioid effect by single-unit extracellular recordings of LC neurons from rat brain slices. Immunocytochemical techniques were also used to evaluate MOR trafficking...
June 7, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28588452/structure-function-analysis-of-the-glyr-%C3%AE-2-subunit-autism-mutation-p-r323l-reveals-a-gain-of-function
#18
Yan Zhang, Thi Nhu Thao Ho, Robert J Harvey, Joseph W Lynch, Angelo Keramidas
Glycine receptors (GlyRs) containing the α2 subunit regulate cortical interneuron migration. Disruption of the GlyR α2 subunit gene (Glra2) in mice leads to disrupted dorsal cortical progenitor homeostasis, leading to a depletion of projection neurons and moderate microcephaly in newborn mice. In humans, rare variants in GLRA2, which is located on the X chromosome, are associated with autism spectrum disorder (ASD) in the hemizygous state in males. These include a microdeletion (GLRA2∆ex8-9) and missense mutations in GLRA2 (p...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28587819/prodepressant-and-anxiogenic-like-effects-of-serotonin-selective-but-not-noradrenaline-selective-antidepressant-agents-in-mice-lacking-%C3%AE-2-containing-gabaa-receptors
#19
Rebecca S Benham, Nishani B Hewage, Raymond F Suckow, Elif Engin, Uwe Rudolph
Deficits in neuronal inhibition via gamma-aminobutyric acid (GABA) type A receptors (GABAA-Rs) are implicated in the pathophysiology of major depressive disorder and the therapeutic effects of current antidepressant treatments, however, the relevant GABAA-R subtype as defined by its alpha subunit is still unknown. We previously reported anxiety- and depressive-like behavior in alpha2+/- and alpha2-/- mice, respectively (Vollenweider, 2011). We sought to determine whether this phenotype could be reversed by chronic antidepressant treatment...
June 3, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28587810/subcellular-localization-of-na-k-atpase-isoforms-in-ventricular-myocytes
#20
Garrick K Yuen, Samuel Galice, Donald M Bers
The sodium/potassium ATPase (NKA) is essential for establishing the normal intracellular [Na(+)] and [K(+)] and transmembrane gradients that are essential for many cellular functions, including cardiac electrophysiology and contractility. Different NKA isoforms exhibit differential expression levels, cellular localization, and function in different tissues and species. Prior work has indicated that the NKA-α1 isoform is quantitatively predominant in cardiac myocytes, but that the α2 isoform is preferentially concentrated in the transverse tubules (TT), possibly at junctions with the sarcoplasmic reticulum (SR) where α2 may preferentially modulate cardiac contractility...
June 3, 2017: Journal of Molecular and Cellular Cardiology
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