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https://www.readbyqxmd.com/read/29775659/%C3%AE-2-receptors-in-the-lateral-parabrachial-nucleus-generates-the-pressor-response-of-the-cardiovascular-chemoreflex-effects-of-gaba-a-receptor
#1
Nafiseh Mirzaei Damabi, Gholam Reza Namvar, Fahimeh Yeganeh, Masoumeh Hatam
The lateral parabrachial nucleus (LPBN) is a pontine area involved in cardiovascular chemoreflex. This study was performed to find the effects of reversible synaptic blockade of the LPBN on the chemoreflex responses, and to find the roles of GABAA receptor and α2 -adenoreceptor (α2 -AR) in chemoreflex. It also aimed to seek possible interaction between GABA and noradrenergic systems of the LPBN in urethane-anesthetized male rats. Cardiovascular chemoreflex was activated by intravenous injection of potassium cyanide (KCN, 80 μg/kg)...
May 15, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29769444/glioblastoma-targeted-cd4-car-t-cells-mediate-superior-antitumor-activity
#2
Dongrui Wang, Brenda Aguilar, Renate Starr, Darya Alizadeh, Alfonso Brito, Aniee Sarkissian, Julie R Ostberg, Stephen J Forman, Christine E Brown
Chimeric antigen receptor-modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2)...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29765374/mica-129-dimorphism-and-soluble-mica-are-associated-with-the-progression-of-multiple-myeloma
#3
Alessandra Zingoni, Elisabetta Vulpis, Francesca Cecere, Maria G Amendola, Daniel Fuerst, Taron Saribekyan, Adnane Achour, Tatyana Sandalova, Ilaria Nardone, Agnese Peri, Alessandra Soriani, Cinzia Fionda, Elena Mariggiò, Maria T Petrucci, Maria R Ricciardi, Joannis Mytilineos, Marco Cippitelli, Cristina Cerboni, Angela Santoni
Natural killer (NK) cells are immune innate effectors playing a pivotal role in the immunosurveillance of multiple myeloma (MM) since they are able to directly recognize and kill MM cells. In this regard, among activating receptors expressed by NK cells, NKG2D represents an important receptor for the recognition of MM cells, being its ligands expressed by tumor cells, and being able to trigger NK cell cytotoxicity. The MHC class I-related molecule A (MICA) is one of the NKG2D ligands; it is encoded by highly polymorphic genes and exists as membrane-bound and soluble isoforms...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29764227/responsiveness-of-%C3%AE-2-adrenoceptor-i1-imidazoline-receptor-in-the-rostral-ventrolateral-medulla-to-cardiovascular-regulation-is-enhanced-in-conscious-spontaneously-hypertensive-rat
#4
Masanobu Yamazato, Minori Nakamoto, Atsushi Sakima, Yoriko Yamazato, Shuichi Takishita, Yusuke Ohya
Stimulation of α2-adrenoceptor/I1-imidazoline receptors in the rostral ventrolateral medulla decreases the blood pressure via sympathoinhibition. However, alteration of receptor responses in genetically hypertensive rats remains unclear. We examined cardiovascular responses of α2-adrenoceptor/I1-imidazoline receptor agonist and antagonists microinjected into the rostral ventrolateral medulla of conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. Injection of 2-nmol clonidine-an α2-adrenoceptor/I1-imidazoline receptor agonist-unilaterally into the rostral ventrolateral medulla decreased the blood pressure, heart rate, and renal sympathetic nerve activity; the responses were significantly enhanced in spontaneously hypertensive rats than in Wistar Kyoto rats...
May 15, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29748580/modulation-of-sympathetic-preganglionic-neuron-activity-via-adrenergic-receptors
#5
Yoshino Minoura, Hiroshi Onimaru, Kamon Iigaya, Youichi Kobayashi
The sympathetic preganglionic neurons (SPNs) play a key role in the sympathetic nervous system. Previous reports have suggested that norepinephrine (NE) directly affects SPNs via both inhibitory hyperpolarization interactions mediated by α2 receptors and excitatory depolarization interactions mediated by α1 receptors. It remains poorly understood, however, whether the excitability of SPNs can be inhibited indirectly (presynaptically) as well as directly (postsynaptically). We intracellularly recorded 41 SPNs using the whole-cell patch-clamp technique in spinal cord slice preparations of neonatal rats...
May 10, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29738700/g-%C3%AE-i-and-g-%C3%AE-%C3%AE-subunits-have-opposing-effects-on-dexmedetomidine-induced-sedation
#6
Meng Liu, Yi Yang, Bo Tan, Yulei Li, Peilan Zhou, Ruibin Su
Dexmedetomidine (DMED) is a potent and highly selective α2 -adrenergic receptor agonist and is widely used for short-term sedation. However, the mechanism of DMED-induced sedation has not been deciphered. In the present study, we investigated the mechanism of Gαi and Gβγ subunits on DMED-induced sedation. An ED50 of DMED-induced loss of righting reflex (200.0nmol/kg) was increased to 375.0 or 433.3nmol/kg after pre-treatment with cAMP analog dbcAMP (50nmol/5μl/mouse, i.c.v.) or the phosphodiesterase 4 inhibitor rolipram (100nmol/5μl/mouse, i...
May 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29736140/antiulcerogenic-activity-of-the-hydroalcoholic-extract-of-leaves-of-annona-muricata-linnaeus-in-mice
#7
Elizângela Beneval Bento, Francisco Elizaudo de Brito Júnior, Dayanne Rakelly de Oliveira, Cícera Norma Fernandes, Gyllyandeson de Araújo Delmondes, Francisco Rafael Alves Santana Cesário, Cristina Kelly de Sousa Rodrigues, Valterlúcio Dos Santos Sales, Francisco Rodolpho Sobreira Dantas Nóbrega de Figueiredo, Izabel Cristina Santiago Lemos, Álefe Brito Monteiro, Irwin Rose Alencar de Menezes, José Galberto Martins da Costa, Marta Regina Kerntopf
Annona muricata Linnaeus, popularly known as "graviola" and also called soursop, is a species typical of countries with a tropical climate, and it is used in folk medicine as an anticancer, analgesic and antispasmodic agent. The aim of the present study was to validate the gastroprotective activity of the hydroalcoholic extract of the leaves of A. muricata (HEAM) and to investigate the underlying mechanisms of action for this effect. Gastric lesions were induced in mice by absolute ethanol, acidified ethanol or indomethacin...
May 2018: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/29729264/dexmedetomidine-attenuates-renal-fibrosis-via-%C3%AE-2-adrenergic-receptor-dependent-inhibition-of-cellular-senescence-after-renal-ischemia-reperfusion
#8
Qijian Li, Chaojin Chen, Xi Chen, Mingming Han, Juan Li
BACKGROUND: Renal ischemia/reperfusion (IR) can induce acute kidney injury (AKI), which often progresses to chronic kidney disease (CKD). Dexmedetomidine (Dex), a highly selective α2 adrenergic receptor (α2-AR) agonist, protects against acute renal IR-induced injury. However, the effects of Dex on the transition of AKI to CKD remain unclear. Therefore, we investigated the mechanisms of Dex on renal fibrosis. METHODS: Adult male C57BL/6 mice were pretreated with Dex, a specific α2A-adrenergic receptor (AR) blocker (BRL-44408), or a cell senescence inhibitor (rapamycin) in a surgical bilateral renal IR model...
May 2, 2018: Life Sciences
https://www.readbyqxmd.com/read/29725523/suppression-of-osteoclastogenesis-via-%C3%AE-2-adrenergic-receptors
#9
Kosuke Hamajima, Kazunori Hamamura, Andy Chen, Hiroki Yokota, Hironori Mori, Shoyoku Yo, Hisataka Kondo, Kenjiro Tanaka, Kyoko Ishizuka, Daisuke Kodama, Takao Hirai, Ken Miyazawa, Shigemi Goto, Akifumi Togari
The sympathetic nervous system is known to regulate osteoclast development. However, the involvement of α2-adrenergic receptors (α2-ARs) in osteoclastogenesis is not well understood. In the present study, their potential role in osteoclastogenesis was investigated. Guanabenz, clonidine and xylazine were used as agonists of α2-ARs, while yohimbine and idazoxan were employed as antagonists. Using RAW264.7 pre-osteoclast and primary bone marrow cells, the mRNA expression of the osteoclast-related genes nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), tartrate-resistant acid phosphatase (TRAP) and cathepsin K was evaluated following induction with receptor activator of nuclear factor κB ligand (RANKL)...
May 2018: Biomedical Reports
https://www.readbyqxmd.com/read/29725338/cd22-binding-synthetic-sialosides-regulate-b-lymphocyte-proliferation-through-cd22-ligand-dependent-and-independent-pathways-and-enhance-antibody-production-in-mice
#10
Naoko Matsubara, Akihiro Imamura, Tatsuya Yonemizu, Chizuru Akatsu, Hongrui Yang, Akiharu Ueki, Natsuki Watanabe, Hajjaj Abdu-Allah, Nobutaka Numoto, Hiromu Takematsu, Shinobu Kitazume, Thomas F Tedder, Jamey D Marth, Nobutoshi Ito, Hiromune Ando, Hideharu Ishida, Makoto Kiso, Takeshi Tsubata
Sialic acid-binding immunoglobulin-like lectins (Siglecs) are expressed in various immune cells and most of them carry signaling functions. High-affinity synthetic sialoside ligands have been developed for various Siglecs. Therapeutic potentials of the nanoparticles and compounds that contain multiple numbers of these sialosides and other reagents such as toxins and antigens have been demonstrated. However, whether immune responses can be regulated by monomeric sialoside ligands has not yet been known. CD22 (also known as Siglec-2) is an inhibitory molecule preferentially expressed in B lymphocytes (B cells) and is constitutively bound and functionally regulated by α2,6 sialic acids expressed on the same cell (cis-ligands)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29720564/evidence-that-sedative-effects-of-benzodiazepines-involve-unexpected-gaba-a-receptor-subtypes-quantitative-observation-studies-in-rhesus-monkeys
#11
Angela N Duke, Zhiqiang Meng, Donna M Platt, John R Atack, Gerard R Dawson, David S Reynolds, V V N Phani Babu Tiruveedhula, Guanguan Li, Michael Rajesh Stephen, Werner Sieghart, James M Cook, James K Rowlett
Using non-human primates, we introduced a new set of behavioral categories for observable sedative effects based on pediatric anesthesiology classifications. We examined the effects of alprazolam and diazepam (non-selective benzodiazepines), zolpidem (preferential binding to α1 subunit-containing GABAA receptors), HZ-166 (8-ethynyl-6-(2'-pyridine)-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester; functionally selective for α2 and α3 subunit-containing GABAA receptors), MRK-696 (7-cyclobutyl-6-(2-methyl-2H-1,2,4-triazol-2-ylmethoxy)-3-(2-flurophenyl)-1,2,4-triazolo(4,3-b)pyridazine; no selectivity but partial intrinsic activity), and TPA023B (6,2'-difluro-5'-(3-(1-hydroxy-1-methylethyl)imidazo(1,2-b((1,2,4)triazin-7-yl)(1,1'-biphenyl)-2-carbonitrile; selectivity for α2, α3, α5 subunit-containing GABAA receptors) using quantitative behavioral observation techniques in rhesus monkeys...
May 2, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29720252/estrogen-induces-st6gal1-expression-and-increases-igg-sialylation-in-mice-and-patients-with-rheumatoid-arthritis-a-potential-explanation-for-the-increased-risk-of-rheumatoid-arthritis-in-postmenopausal-women
#12
Cecilia Engdahl, Albert Bondt, Ulrike Harre, Jasmin Raufer, René Pfeifle, Alessandro Camponeschi, Manfred Wuhrer, Michaela Seeling, Inga-Lill Mårtensson, Falk Nimmerjahn, Gerhard Krönke, Hans U Scherer, Helena Forsblad-d'Elia, Georg Schett
BACKGROUND: Rheumatoid arthritis (RA) preferentially affects women, with the peak incidence coinciding with estrogen decrease in menopause. Estrogen (E2) may therefore have intrinsic immune-regulatory properties that vanish with menopause. Fc sialylation is a crucial factor determining the inflammatory effector function of antibodies. We therefore analyzed whether E2 affects immunoglobulin G (IgG) sialylation. METHODS: Postmenopausal (ovariectomized) mice were immunized with ovalbumin and treated with E2 or vehicle...
May 2, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29717262/glycosylation-controls-cooperative-pecam-vegfr2-%C3%AE-3-integrin-functions-at-the-endothelial-surface-for-tumor-angiogenesis
#13
Rie Imamaki, Kazuko Ogawa, Yasuhiko Kizuka, Yusuke Komi, Soichi Kojima, Norihiro Kotani, Koichi Honke, Takashi Honda, Naoyuki Taniguchi, Shinobu Kitazume
Most of the angiogenesis inhibitors clinically used in cancer treatment target the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway. However, the current strategies for treating angiogenesis have limited efficacy. The issue of how to treat angiogenesis and endothelial dysfunction in cancer remains a matter of substantial debate. Here we demonstrate a glycosylation-dependent regulatory mechanism for tumor angiogenesis. St6gal1-/- mice, lacking the α2,6-sialylation enzyme, were shown to exhibit impaired tumor angiogenesis through enhanced endothelial apoptosis...
May 2, 2018: Oncogene
https://www.readbyqxmd.com/read/29715490/an-antidepressant-related-pharmacological-signature-for-positive-allosteric-modulators-of-%C3%AE-2-3-containing-gaba-a-receptors
#14
K R Methuku, X Li, R Cerne, S D Gleason, J M Schkeryantz, V V N P B Tiruveedhula, L K Golani, G Li, M M Poe, Md T Rahman, J M Cook, J L Fisher, J M Witkin
Data from transgenic animals and novel pharmacological agents has realigned scientific scrutiny on the therapeutic potential of positive allosteric modulators (PAMs) of α2/3-containing GABAA receptors. Evidence for analgesic, anticonvulsant, and anxiolytic activity of α2/3-selective PAMs has been presented along with the clinical potential for a milder motor-impacting profile compared to non-selective GABAA receptor PAMs. A new series of α2/3-selective PAMs was recently introduced which has anxiolytic and anticonvulsant activity in rodent models...
April 28, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29715454/-effect-of-polygodial-and-its-direct-derivatives-on-the-mammalian-na-k-atpase-activity
#15
Diogo Gomes Garcia, Cassiano Felippe Gonçalves-de-Albuquerque, Camila Ignácio da Silva, Robert Kiss, Ramesh Dasari, Sunena Chandra, Alexander Kornienko, Patricia Burth
The sesquiterpene polygodial is an agonist of the transient receptor potential vanilloid 1 (TRPV1). Our group recently reported the synthesis and anticancer effects of polygodial and its derivatives, and showed that these compounds retain activity against apoptosis- and multidrug-resistant cancer cells. Herein, we tested the inhibitory effect of these compounds on the activity of the enzyme Na+ /K+ -ATPase (NKA) from kidney (α1 isoform) and brain (α2 and α3 isoforms) guinea pig extracts. Polygodial (1) displayed a dose-dependent inhibition of both kidney and brain purified NKA preparations, with higher sensitivity for the cerebral isoforms...
April 28, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29713337/alternagin-c-binding-to-%C3%AE-2-%C3%AE-1-integrin-controls-matrix-metalloprotease-9-and-matrix-metalloprotease-2-in-breast-tumor-cells-and-endothelial-cells
#16
Milene Nóbrega de Oliveira Moritz, Lívia Mara Santos Eustáquio, Kelli Cristina Micocci, Ana Carolina Caetano Nunes, Patty Karina Dos Santos, Tamires de Castro Vieira, Heloísa Sobreiro Selistre-de-Araujo
Background: Matrix metalloproteinases (MMPs) are key players in tumor progression, helping tumor cells to modify their microenvironment, which allows cell migration to secondary sites. The role of integrins, adhesion receptors that connect cells to the extracellular matrix, in MMP expression and activity has been previously suggested. However, the mechanisms by which integrins control MMP expression are not completely understood. Particularly, the role of α2β1 integrin, one of the major collagen I receptors, in MMP activity and expression has not been studied...
2018: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/29710514/pathophysiological-investigations-anxiolytic-effects-and-interaction-of-a-semisynthetic-riparin-with-benzodiazepine-receptors
#17
Éverton José Ferreira de Araújo, Luís Mário Rezende-Júnior, Layana Karine Farias Lima, Marcelo Pereira da Silva-Júnior, Oskar Almeida Silva, Benedito Pereira de Sousa Neto, Antonia Amanda Cardoso de Almeida, Stanley Juan Chavez Gutierrez, Adriana da Rocha Tomé, Luciano da Silva Lopes, Paulo Michel Pinheiro Ferreira, Francisco das Chagas Alves Lima
We have reported Riparin A as a promising antiparasitic molecule ​​against Leishmania amazonensis promastigotes. This work evaluated the acute oral toxicity of Riparin A and its anxiolytic effects using in vivo models and computational tools. Mice were submitted to acute oral toxicity tests (Guideline OECD 423). Later, anxiety assays with Riparin A (50, 100 and 200 mg/kg: elevated plus maze, light/dark box and marble burying) were performed. Theoretical calculations analyzed interaction of Riparin A with gamma-amino butyric acid (GABA) receptors...
April 24, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29708589/impaired-modulation-of-postjunctional-%C3%AE-1-but-not-%C3%AE-2-adrenergic-vasoconstriction-in-contracting-forearm-muscle-of-postmenopausal-women
#18
Nicholas T Kruse, William E Hughes, Kenichi Ueda, Satoshi Hanada, Andrew J Feider, Erika Iwamoto, Joshua M Bock, Darren P Casey
Contraction mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in older males; however, direct confirmation of this effect remains unknown in postmenopausal women (PMW). The present study examined whether PMW exhibit augmented postjunctional α-adrenergic receptor vasoconstriction at rest and during forearm exercise compared to young women (YW). Eight YW (24 ± 1 yrs) and eight PMW (65 ± 1 yrs) completed a series of randomized experimental trials; 1) at rest 2) under high flow (adenosine infusion) conditions and 3) during 6-minutes of forearm exercise at relative (20% of maximum (MVC) and absolute (7 kg) intensities...
April 30, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29704000/glutamatergic-and-gabaergic-ventral-bnst-neurons-differ-in-their-physiological-properties-and-responsiveness-to-noradrenaline
#19
Nur Zeynep Gungor, Ryo Yamamoto, Denis Pare
The bed nucleus of the stria terminalis (BNST) regulates defensive responses to threats and its anteroventral portion (BNST-AV) is involved. BNST-AV contains a minority of glutamatergic neurons scattered among a dominant population of GABAergic cells. There is evidence that these two cell types might exert opposite influences, the former promoting and the latter reducing anxiety. Although GABAergic cells greatly outnumber glutamatergic neurons in BNST-AV, in some circumstances the influence of glutamatergic cells appears to predominate...
April 20, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29700767/effects-of-post-weaning-chronic-stress-on-nociception-spinal-cord-%C3%AE-opioid-and-%C3%AE-2-adrenergic-receptors-expression-in-rats-and-their-offspring
#20
Asef Hormozi, Asadollah Zarifkar, Mohsen Tatar, Mahdi Barazesh, Bahar Rostami
Stressful situations can change biological process in human and animal, and some of these changes may transfer to the next generations. We used a communication box to induce chronic electrical foot-shock stress in rats. Tail flick latency and formalin test were done to determine the level of pain sensation. Real-time RT-PCR was used to measure the level of spinal cord μ-opioid (MOR) and α2-adrenergic receptors (α2-AR) mRNA. We demonstrate that chronic stress can change nociception and leads to hyperalgesia...
April 26, 2018: Journal of Molecular Neuroscience: MN
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