journal
MENU ▼
Read by QxMD icon Read
search

Journal of Pharmacology and Experimental Therapeutics

journal
https://www.readbyqxmd.com/read/28209723/functional-metabolic-and-dynamic-mitochondrial-changes-in-the-rat-cirrhosis-hepatocellular-carcinoma-model-and-the-protective-effect-of-ifc-305
#1
Enrique Chavez, Maria Guadalupe Lozano-Rosas, Mariana Dominguez-Lopez, Gabriela Velasco-Loyden, Jesus Rafael Rodriguez-Aguilera, Concepcion Jose-Nunez, Marietta Tuena de Gomez-Puyou, Victoria Chagoya de Sanchez
BACKGROUND: Mitochondrion is an important metabolic and energetic organelle which regulates several cellular processes. Mitochondrial dysfunction has been related with liver diseases including hepatocellular carcinoma. As a result, the energetic demand is not properly supplied and mitochondrial morphologic changes has been observed resulting in an altered metabolism. We previously demonstrated the chemopreventive effect of the hepatoprotector IFC-305. AIM: In this work we aimed to evaluate the functional, metabolic, and dynamic mitochondrial alterations in the sequential model of cirrhosis-hepatocellular carcinoma induced by diethylnitrosamine in rats and the possible beneficial effect of IFC-305...
February 16, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28196836/label-free-dynamic-mass-redistribution-reveals-low-density-pro-survival-%C3%AE-1b-adrenergic-receptors-in-human-sw480-colon-carcinoma-cells
#2
Dorathy-Ann Harris, Ji-Min Park, Kyung Soon-Lee, Cong Xu, Nephi Stella, Chris Hague
Small molecules that target the adrenergic family of G protein-coupled receptors (GPCRs) show promising therapeutic efficacy for the treatment of various cancers. Herein, we report that human colon cancer cell line SW480 expresses low-density functional α1B-adrenergic receptors (ARs) as revealed by label-free dynamic mass redistribution (DMR) signaling technology and confirmed by quantitative reverse-transcriptase polymerase chain reaction analysis. Remarkably, while endogenous α1B-ARs are not detectable via either [3H]-prazosin binding analysis or phosphoinositol hydrolysis assays, their activation leads to robust DMR and enhanced cell viability...
February 14, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28193636/evaluation-of-jak3-biology-in-autoimmune-disease-using-a-highly-selective-irreversible-jak3-inhibitor
#3
Fiona Elwood, David Witter, Jennifer Piesvaux, Brian Kraybill, Nathan Bays, Carla Alpert, Peter Goldenblatt, Yujie Qu, Irena Ivanovska, Hyun-Hee Lee, Chi-Sung Chiu, Hao Tang, Mark E Scott, Sujal Deshmukh, Mark Zielstorff, Alan Byford, Kalyan Chakravarty, Lauren Dorosh, Alexy Rivkin, Joel Klappenbach, Bo-Sheng Pan, Ilona Kariv, Christopher Dinsmore, Deborah Slipetz, Peter Dandliker
Reversible Janus kinase (JAK) inhibitors such as Tofacitinib(Changelian, et al., 2003;Flanagan, et al., 2010) and Decernotinib(Farmer, et al., 2015;Mahajan, et al., 2015) block cytokine signaling and are efficacious in treating autoimmune diseases (Kremer, et al., 2009;Fleischmann, et al., 2015;Fleischmann, et al., 2015;Krueger, et al., 2016;Sandborn, et al., 2012). However therapeutic doses are limited due to inhibition of other JAK/STAT pathways associated with hematopoiesis, lipid biogenesis, infection and immune responses(Kahn C, 2012)...
February 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28188270/dual-mechanism-for-inhibition-of-inwardly-rectifying-kir2-x-channels-by-quinidine-involving-direct-pore-block-and-pip2-interference
#4
Christoph Koepple, Daniel Scherer, Claudia Seyler, Eberhard Scholz, Dierk Thomas, Hugo A Katus, Edgar Zitron
Class IA antiarrhythmic drug quinidine was one of the first clinically used compounds to terminate atrial fibrillation and acts as multichannel inhibitor with well-documented inhibitory effects on several cardiac potassium channels. In the mammalian heart, heteromeric assembly of Kir2.1-2.3 channels underlies IK1 current. While a low-affinity block of quinidine on Kir2.1 has already been described, a comparative analysis of effects on other Kir2.x channels has not been performed to date. Therefore, we analyzed the effects of quinidine on wild type and mutant Kir2...
February 10, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28179474/individual-differences-in-the-relative-reinforcing-effects-of-3-4-methylenedioxypyrovalerone-mdpv-under-fixed-and-progressive-ratio-schedules-of-reinforcement-in-rats
#5
Brenda M Gannon, Kayla I Galindo, Kenner C Rice, Gregory T Collins
The recreational use of designer drugs, including synthetic cathinones (bath salts), is associated with high levels of abuse and toxicity, and represents a growing threat to public health. MDPV (3,4-methylenedioxypyrovalerone) is a cocaine-like monoamine uptake inhibitor, and one of the most widely available and abused synthetic cathinones. The present study used male Sprague-Dawley rats to directly compare: (1) the acquisition of responding for MDPV and cocaine under a fixed ratio (FR) 1 schedule of reinforcement; (2) full dose-response curves for MDPV and cocaine under FR5; and (3) progressive ratio (PR) schedules of reinforcement...
February 8, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28179473/dynamic-regulation-of-homer-binding-to-group-i-mglurs-by-preso1-and-converging-kinase-cascades
#6
Jia-Hua Hu, Paul F Worley, Paul Kammermeier
In rat sympathetic neurons from the superior cervical ganglia (SCG) expressing metabotropic glutamate receptors (mGluRs) 1 or 5, overexpression of scaffolding Homer proteins, which bind to a Homer ligand in their C-termini, cause receptor clustering and uncoupling from ion channel modulation. In the absence of recombinant Homer protein overexpression, uncoupling of mGluRs from voltage dependent channels can be induced by expression of Preso1, an adaptor of proline directed kinases that phosphorylates the Homer ligand and recruits binding of endogenous Homer proteins...
February 8, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28179472/endothelin-confers-protection-against-high-glucose-induced-neurotoxicity-via-alleviation-of-oxidative-stress
#7
Mohamed Fouda, Abdel A Abdel-Rahman
Recent findings linked the inhibition in the neuromodulator peptide endothelin-1 (ET-1) level to the high glucose-evoked neurotoxicity. However, definitive neuroprotective role for ET-1, and the major neuronal ET (ET-3), against high glucose-evoked toxicity, and the implicated neurochemical responses triggered by their ET-A and ET-B receptors remain unknown. Here, we tested the hypothesis that ET-B activation alleviates high glucose-evoked oxidative stress and cell death. High glucose (100 mM for 48 hrs.)-evoked cell death was associated with elevation in reactive oxygen species, inhibition of catalase activity, and a paradoxical upregulation of hemeoxygenase-1 expression along with ET-A and ET-B receptors were down-regulated and up-regulated, respectively...
February 8, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28174211/overlapping-and-divergent-actions-of-structurally-distinct-hdac-inhibitors-in-cardiac-fibroblasts
#8
Katherine B Schuetze, Matthew S Stratton, Weston W Blakeslee, Michael F Wempe, Florence F Wagner, Edward B Holson, Yin-Ming Kuo, Andrew J Andrews, Tonya M Gilbert, Jacob M Hooker, Timothy A McKinsey
Inhibitors of zinc-dependent histone deacetylases (HDACs) profoundly impact cellular function by altering gene expression via changes in nucleosomal histone tail acetylation. Historically, investigators have employed pan-HDAC inhibitors, such as the hydroxamate trichostatin A (TSA), which simultaneously targets members of each of the three zinc-dependent HDAC classes (classes I, II and IV). More recently, class- and isoform-selective HDAC inhibitors have been developed, providing invaluable chemical biology probes for dissecting the roles of distinct HDACs in the control of various physiological and pathophysiological processes...
February 7, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28167639/therapeutic-restoration-of-endothelial-glycocalyx-in-sepsis
#9
Jong Wook Song, Joseph A Zullo, Dionysios Liveris, Matthew Dragovich, X Frank Zhang, Michael S Goligorsky
Endothelial glycocalyx (EG) is disintegrated during sepsis. We showed (Am J Pathol, 2016) that this occurs very early in the course of sepsis and its prevention improves survival of mice with sepsis. Here, we sought to investigate the possibility to pharmacologically accelerate the restoration of disintegrated EG in sepsis. We used a soilage injection model to induce polymicrobial sepsis in C57/BL6 mice and measured total body EG. En face aortic preparations were used for staining for markers of EG and atomic force microscopy (AFM) was used to measure EG in vitro...
February 6, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28167638/effects-of-repeated-ropinirole-treatment-on-phencyclidine-induced-hyperlocomotion-prepulse-inhibition-deficits-and-social-avoidance-in-rats
#10
Amanda M Maple, Tanessa Call, Phylicia C Kimmel, Ronald P Hammer
Phencyclidine (PCP), a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist, provides the most complete pharmacological model of schizophrenia in humans and animals. Acute PCP causes hyperlocomotion, disrupts prepulse inhibition (PPI), and increases social avoidance in rats. We previously showed that repeated treatment with the dopamine (DA) D2-like receptor agonists, quinpirole or ropinirole, prevents agonist-induced PPI disruption. The present study examines whether repeated ropinirole treatment similarly attenuates the effects of PCP in a more complete model of schizophrenia symptoms...
February 6, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28154014/a-tumor-cell-selective-inhibitor-of-mitogen-activated-protein-kinase-phosphatases-sensitizes-breast-cancer-cells-to-lymphokine-activated-killer-cell-activity
#11
Christof T Kaltenmeier, Laura L Vollmer, Lawrence A Vernetti, Lindsay Caprio, Keanu Davis, Vasiliy N Korotchenko, Billy W Day, Michael Tsang, Keren I Hulkower, Michael T Lotze, Andreas Vogt
Dual specificity mitogen activated protein kinase (MAPK) phosphatases (DUSP-MKPs) have been hypothesized to maintain cancer cell survival by buffering excessive MAPK signaling caused by upstream activating oncogenic products. A large and diverse body of literature suggests that genetic depletion of DUSP-MKPs can reduce tumorigenicity, suggesting that hyperactivating MAPK signaling by DUSP-MKP inhibitors could be a novel strategy to selectively affect the transformed phenotype. Through in vivo structure activity relationship studies in transgenic zebrafish we recently identified a hyperactivator of Fibroblast Growth Factor signaling (BCI-215) that is devoid of developmental toxicity and restores defective MAPK activity caused by overexpression of DUSP1 and DUSP6 in mammalian cells...
February 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28148637/impact-of-nonalcoholic-fatty-liver-disease-on-toxicokinetics-of-tetrachloroethylene
#12
Joseph A Cichocki, Shinji Furuya, Kranti Konganti, Yu-Syuan Luo, Thomas J McDonald, Yasuhiro Iwata, Weihsueh A Chiu, David W Threadgill, Igor P Pogribny, Ivan Rusyn
Lifestyle factors and chronic pathological states are important contributors to inter-individual variability in susceptibility to xenobiotic-induced toxicity. Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition that can dramatically affect chemical metabolism. We examined the effect of NAFLD on toxicokinetics of tetrachloroethylene (PERC), a ubiquitous environmental contaminant that requires metabolic activation to induce adverse health effects. Mice (C57Bl/6J, male) were fed a low-fat diet (LFD), high fat diet (HFD), or methionine/folate/choline-deficient diet (MCD) to model a healthy liver, steatosis, or nonalcoholic steatohepatitis (NASH), respectively...
February 1, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28138042/control-of-neurotransmission-by-nav1-7-in-human-guinea-pig-and-mouse-airway-parasympathetic-nerves
#13
Michaela Kocmalova, Marian Kollarik, Brendan J Canning, Fei Ru, Robert A Herbstromer, Sonya Meeker, Silvia Fonquerna, Monica Aparici, Montserrat Miralpeix, Xian Chi, Baolin Li, Ben Wilenkin, Jeff McDermott, Eric Nisenbaum, Jeff Krajewski, Bradley J Undem
Little is known about the voltage-gated sodium channels (NaVs) that control neurotransmission in the parasympathetic nervous system. We evaluated the expression of the α subunits of each of the nine NaVs in human, guinea pig, and mouse airway parasympathetic ganglia. We combined this information with a pharmacological analysis of selective NaV blockers on parasympathetic contractions of isolated airway smooth muscle. As would be expected from previous studies, tetrodotoxin potently blocked the parasympathetic responses in the airways of each species...
January 30, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28138041/translational-pharmacology-of-the-mglur2-preferring-agonist-ly2812223-in-animal-and-human-brain
#14
Christian C Felder, Douglas A Schober, Yuan Tu, Anne T Quets, Hongling Xiao, Marla Watt, Edward R Siuda, Eric S Nisenbaum, Chuanix Xiang, Beverly Heinz, Lourdes Prieto, David L Mc Kinzie, James A Monn
LY2812223 was identified via structure-activity studies arising from the potent mGlu2/3 receptor agonist LY354740 as a selective mGlu2 agonist. This pharmacology was determined using cells stably transfected cells either containing the human mGlu2 or mGlu3 receptor. We extended the pharmacological evaluation of LY2812223 to native brain tissues derived from relevant species used for preclinical drug development as well as human post mortem brain tissue. This analysis was conducted to ensure pharmacological translation from animals to human subjects in subsequent clinical studies...
January 30, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28138040/comparative-effects-of-ly3020371-a-potent-and-selective-mglu2-3-receptor-antagonist-and-ketamine-a-non-competitive-nmda-receptor-antagonist-in-rodents-evidence-supporting-use-for-the-treatment-of-depression
#15
Jeffrey M Witkin, Stephen Mitchell, Keith Wafford, Guy Carter, Gary Gilmour, Jennifer Li, Brian Eastwood, Carl Overshiner, Xia Li, Linda Rorick-Kehn, Kurt Rasmussen, Wesley Anderson, Alexander Nikolayev, Vladamir Tolstikov, Ming-Shang Kuo, John Catlow, Renhua Li, Stephen Smith, Charles Mitch, Paul Ornstein, Stephen Swanson, James Monn
The ability of the NMDA receptor antagonist ketamine to alleviate symptoms in patients suffering from treatment resistant depression (TRD) is well documented. In this report, we directly compare in vivo biological responses in rodents elicited by a recently discovered mGlu2/3 receptor antagonist (LY3020371) with those produced by ketamine. Both LY3020371 and ketamine increased the number of spontaneously active DA cells in the ventral tegmental area of anesthetized rats, increased O2 in the anterior cingulate cortex, promoted wakefulness, enhanced the efflux of biogenic amines in the prefrontal cortex, and produced antidepressant-related behavioral effects in SSRI-sensitive and -insensitive rodent models...
January 30, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28130265/effect-of-tamoxifen-and-brain-penetrant-pkc-and-jnk-inhibitors-on-tolerance-to-opioid-induced-respiratory-depression-in-mice
#16
Sarah L Withey, Rob Hill, Abigail Lyndon, William L Dewey, Eamonn Kelly, Graeme Henderson
Respiratory depression is the major cause of death in opioid overdose. We have previously shown that prolonged treatment of mice with morphine induces profound tolerance to the respiratory depressant effects of the drug (Hill et al., 2016, Neuropsychopharmacol 41:762-773). The aim of the present study was to investigate whether tolerance to opioid-induced respiratory depression is mediated by protein kinase C (PKC) and/or c-Jun N-terminal kinase (JNK). We found that whilst mice treated for up to six days with morphine developed tolerance, as measured by the reduced responsiveness to an acute challenge dose of morphine, administration of the brain-penetrant PKC inhibitors tamoxifen and calphostin C, restored the ability of acute morphine to produce respiratory depression in morphine-treated mice...
January 27, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28123046/pde5-inhibitor-tadalafil-and-hydroxychloroquine-co-treatment-provides-synergistic-protection-against-type-2-diabetes-and-myocardial-infarction-in-mice
#17
Rui Wang, Lei Xi, Rakesh C Kukreja
Diabetes is associated with high risk of ischemic heart disease. We previously showed that phosphodiesterase 5 inhibitor - tadalafil (TAD) induces cardioprotection against ischemia/ reperfusion (I/R) injury in diabetic mice. Hydroxychloroquine (HCQ) is a widely used antimalarial and anti-inflammatory drug, which was reported to reduce hyperglycemia in diabetic patients. Therefore we hypothesized that combination of TAD and HCQ may induce synergistic cardioprotection in diabetes. We also investigated the role of insulin-Akt-mTOR signaling, which regulates protein synthesis and cell survival...
January 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28115553/antidepressant-potential-of-r-ketamine-in-rodent-models-comparison-with-s-ketamine
#18
Kenichi Fukumoto, Hidetoh Toki, Michihiko Iijima, Takashi Hashihayata, Jun-Ichi Yamaguchi, Kenji Hashimoto, Shigeyuki Chaki
The rapid-acting and long-lasting antidepressant effects of (R,S)-ketamine have recently gained much attention. Although (S)-ketamine has been studied as an active isomer, recent evidence has suggested that (R)-ketamine exhibits longer-lasting antidepressant effects than (S)-ketamine in rodents. However, the antidepressant potential of (R)-ketamine has not been fully addressed. In the present study, we compared the antidepressant effects of (R)-ketamine with those of (S)-ketamine in animal models of depression, including a model that is refractory to current medications...
January 23, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28115552/xenin-augments-duodenal-anion-secretion-via-activation-of-afferent-neural-pathways
#19
Izumi Kaji, Yasutada Akiba, Ikuo Kato, Koji Maruta, Atsukazu Kuwahara, Jonathan D Kaunitz
Xenin-25, a neurotensin (NT)-related anorexigenic gut hormone generated mostly in the duodenal mucosa, is believed to increase the rate of duodenal ion secretion, since xenin-induced diarrhea is not present after Roux-en-Y gastric bypass surgery. Since the local effects of xenin on duodenal ion secretion have remained uninvestigated, we thus examined the neural pathways underlying xenin-induced duodenal anion secretion. Intravenous infusion of xenin-8, a bioactive C-terminal fragment of xenin-25, dose-dependently increased the rate of duodenal HCO3- secretion in perfused duodenal loops of anesthetized rats...
January 23, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28115551/early-detection-of-acute-drug-induced-liver-injury-in-mice-by-non-invasive-nir-fluorescence-imaging
#20
Kristine O Vasquez, Jeffrey D Peterson
Hepatocellular and cholestatic forms of drug induced liver injury (DILI) are major reasons for late stage termination of small molecule drug discovery research projects. Biochemical serum markers are limited in their ability to sensitively and specifically detect both of these common DILI forms in preclinical models, and tissue-specific approaches to assessing this are labor intensive, requiring extensive animal dosing, tissue preparation, and pathology assessment. In vivo fluorescent imaging offers non-invasive detection of biological changes detected directly in the livers of living animals...
January 23, 2017: Journal of Pharmacology and Experimental Therapeutics
journal
journal
23880
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"