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Journal of Pharmacological Sciences

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https://www.readbyqxmd.com/read/29146480/neuroprotection-by-chotosan-a-kampo-formula-against-glutamate-excitotoxicity-involves-the-inhibition-of-glun2b-but-not-glun2a-containing-nmda-receptor-mediated-responses-in-primary-cultured-cortical-neurons
#1
Sachie Sasaki-Hamada, Azusa Suzuki, Emi Sanai, Kinzo Matsumoto, Jun-Ichiro Oka
Chotosan (CTS), a traditional herbal formula called Kampo medicine, was shown to be effective in the treatment of vascular dementia in a clinical study, and exerted protective effects against transient cerebral ischemia-induced cognitive impairment in mice. In the present study, we investigated the neuroprotective effects of CTS using primary cultured rat cortical neurons. CTS (250-1000 μg/mL) inhibited neuronal death induced by 100 μM glutamate. This glutamate-induced neuronal death was blocked by a GluN2B-, but not GluN2A-containing NMDA receptor antagonist...
November 1, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29132796/old-drug-new-indication-olsalazine-sodium-reduced-serum-uric-acid-levels-in-mice-via-inhibiting-xanthine-oxidoreductase-activity
#2
Yanfen Niu, Hongjian Li, Lihui Gao, Hua Lin, Hsiangfu Kung, Marie Chia-Mi Lin, Kwong-Sak Leung, Man-Hon Wong, Wenyong Xiong, Ling Li
Hyperuricemia, a long-term purine metabolic disorder, is a well-known risk factor for gout, hypertension and diabetes. In maintaining normal whole-body purine levels, xanthine oxidase (XOD) is a key enzyme in the purine metabolic pathway, as it catalyzes the oxidation of hypoxanthine to xanthine and finally to uric acid. Here we used the protein-ligand docking software idock to virtually screen potential XOD inhibitors from 3167 approved small compounds/drugs. The inhibitory activities of the ten compounds with the highest scores were tested on XOD in vitro...
October 31, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29122532/pathological-prolongation-of-action-potential-duration-as-a-cause-of-the-reduced-alpha-adrenoceptor-mediated-negative-inotropy-in-streptozotocin-induced-diabetic-mice-myocardium
#3
Haruna Kanae, Shogo Hamaguchi, Yumi Wakasugi, Taichi Kusakabe, Keisuke Kato, Iyuki Namekata, Hikaru Tanaka
Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice...
October 31, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29113791/pd149163-induces-hypothermia-to-protect-against-brain-injury-in-acute-cerebral-ischemic-rats
#4
Teng-Fei Xue, Xu Ding, Juan Ji, Hui Yan, Ji-Ye Huang, Xu-Dong Guo, Jin Yang, Xiu-Lan Sun
Therapeutic hypothermia is a promising strategy for acute cerebral ischemia via physical or pharmacological methods. In this study, we pharmacologically induced hypothermia on Sprague Dawley rats by intraperitoneally injecting PD149163. We found that mild hypothermia was induced by PD149163 treatment without local cerebral blood flow (LCBF) alteration. To evaluate the neuroprotective effects of PD149163, TTC staining, HE staining and Nissl's staining were performed in our study. We found that PD149163 could prevent neuronal damage, and inhibit proliferation and activation of glial cells induced by ischemia...
October 23, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29113790/the-persistent-inhibitory-properties-of-saxagliptin-on-renal-dipeptidyl-peptidase-4-studies-with-hk-2-cells-in%C3%A2-vitro-and-normal-rats-in%C3%A2-vivo
#5
Masako Uchii, Mariko Sakai, Yuhei Hotta, Satoshi Saeki, Naoya Kimoto, Akinori Hamaguchi, Tetsuya Kitayama, Shunji Kunori
Saxagliptin, a potent and selective DPP-4 inhibitor, exhibits a slow dissociation from DPP-4. We investigated the sustained effects of saxagliptin on renal DPP-4 activity in a washout study using renal tubular (HK-2) cells, and in a pharmacodynamic study using normal rats. In HK-2 cells, the inhibitory potency of saxagliptin on DPP-4 activity persisted after washout, while that of sitagliptin was clearly reduced. In normal rats, a single treatment of saxagliptin or sitagliptin inhibited the plasma DPP-4 activity to similar levels...
October 23, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29107444/dopamine-d2l-receptor-interacting-proteins-regulate-dopaminergic-signaling
#6
REVIEW
Norifumi Shioda
Dopamine receptor family proteins include seven transmembrane and trimeric GTP-binding protein-coupled receptors (GPCRs). Among them, the dopamine D2 receptor (D2R) is most extensively studied. All clinically used antipsychotic drugs serve as D2R antagonists in the mesolimbic dopamine system, and their ability to block D2R signaling is positively correlated with antipsychotic efficiency. Human genetic studies also show a significant association of DRD2 polymorphisms with disorders including schizophrenia and Parkinson's disease...
October 14, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29129584/high-salt-loading-induces-urinary-storage-dysfunction-via-upregulation-of-epithelial-sodium-channel-alpha-in-the-bladder-epithelium-in-dahl-salt-sensitive-rats
#7
Seiji Yamamoto, Yuji Hotta, Kotomi Maeda, Tomoya Kataoka, Yasuhiro Maeda, Takashi Hamakawa, Yasuhiro Shibata, Shoichi Sasaki, Shinya Ugawa, Takahiro Yasui, Kazunori Kimura
We aimed to investigate whether high salt intake affects bladder function via epithelial sodium channel (ENaC) by using Dahl salt-resistant (DR) and salt-sensitive (DS) rats. Bladder weight of DR + high-salt diet (HS, 8% NaCl) and DS + HS groups were significantly higher than those of DR + normal-salt diet (NS, 0.3% NaCl) and DS + NS groups after one week treatment. We thereafter used only DR + HS and DS + HS group. Systolic and diastolic blood pressures were significantly higher in DS + HS group than in DR + HS group after the treatment period...
October 10, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29056256/glibenclamide-inhibits-nlrp3-inflammasome-mediated-il-1%C3%AE-secretion-in-human-trophoblasts
#8
Kazuhiro Tamura, Gen Ishikawa, Mikihiro Yoshie, Wakana Ohneda, Akihito Nakai, Toshiyuki Takeshita, Eiichi Tachikawa
Infection-associated pregnancy complications cause premature delivery. Caspase-1 is involved in the maturation of interleukin (IL)-1β, which is activated by the NLRP3 inflammasome. To characterize the significance of the NLRP3 inflammasome pathway in the placenta, the effects of activators and inhibitors on NLRP3-related molecules were examined using isolated primary trophoblasts. Caspase-1 and IL-1β mRNA expression was markedly increased in response to lipopolysaccharide (LPS), a toll-like receptor (TLR)4 ligand...
October 6, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29110956/activation-inhibitors-of-nuclear-factor-kappa-b-protect-neurons-against-the-nmda-induced-damage-in-the-rat-retina
#9
Kenji Sakamoto, Tatsuya Okuwaki, Hiroko Ushikubo, Asami Mori, Tsutomu Nakahara, Kunio Ishii
We reported that high-mobility group Box-1 (HMGB1) was involved in excitoneurotoxicity in the retina. HMGB1 is known to activate nuclear factor kappa B (NF-κB). However, the role of NF-κB in excitotoxicity is still controversial. Here, we demonstrated that NF-κB activation induced by NMDA led to the retinal neurotoxicity. Male Sprague-Dawley rats were used, and NMDA (200 nmol/eye) and bovine HMGB1 (15 μg/eye) were intravitreally injected. Triptolide (500 pmol/eye), BAY 11-7082 (500 pmol/eye), and IMD-0354 (7...
September 29, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28982598/methyleugenol-protects-against-t-bhp-triggered-oxidative-injury-by-induction-of-nrf2-dependent-on-ampk-gsk3%C3%AE-and-erk-activation
#10
Junfeng Zhou, Xiaoyuan Ma, Yan Cui, Yang Song, Lei Yao, Yuanyuan Liu, Shanshan Li
Methyleugenol (Mlg), a natural ingredient of many herbs and used as a flavoring substance in dietary products, inhibits inflammation and oxidative stress. The aim of the study is to explore the antioxidative potential of Mlg against tert-butyl hydroperoxide (t-BHP)-triggered oxidative injury and the involvement of antioxidative mechanisms. Our findings indicated that Mlg exposure significantly alleviated t-BHP-stimulated cytotoxicity, suppressed reactive oxygen species (ROS) generation, and increased superoxide dismutase (SOD) and glutathione (GSH) levels, which were related to the induction of the glutamate-cysteine ligase catalytic/modifier (GCLC/GCLM) subunit, heme oxygenase-1 (HO-1), and NAD (P) H: quinone oxidoreductase (NQO1) largely dependent upon upregulating the nuclear factor-erythroid 2-related factor 2 (Nrf2) induction, inhibiting the Keap1 protein expression, and heightening the antioxidant response element (ARE) activity...
September 19, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29110957/a-protease-activated-receptor-1-antagonist-protects-against-podocyte-injury-in-a-mouse-model-of-nephropathy
#11
Yu Guan, Daisuke Nakano, Yifan Zhang, Lei Li, Wenhua Liu, Motohiro Nishida, Takashige Kuwabara, Asahiro Morishita, Hirofumi Hitomi, Kiyoshi Mori, Masashi Mukoyama, Tsutomu Masaki, Katsuya Hirano, Akira Nishiyama
The kidney expresses protease-activated receptor-1 (PAR-1). PAR-1 is known as a thrombin receptor, but its role in kidney injury is not well understood. In this study, we examined the contribution of PAR-1 to kidney glomerular injury and the effects of its inhibition on development of nephropathy. Mice were divided into 3 groups: control, doxorubicin + vehicle (15 mg/kg doxorubicin and saline) and doxorubicin + Q94 (doxorubicin at 15 mg/kg and the PAR-1 antagonist Q94 at 5 mg/kg/d) groups. Where indicated, doxorubicin was administered intravenously and PAR-1 antagonist or saline vehicle by subcutaneous osmotic mini-pump...
September 14, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28966102/prostaglandin-e2-facilitates-neurite-outgrowth-in-a-motor-neuron-like-cell-line-nsc-34
#12
Hiroshi Nango, Yasuhiro Kosuge, Hiroko Miyagishi, Kosuke Sugawa, Yoshihisa Ito, Kumiko Ishige
Prostaglandin E2 (PGE2) exerts various biological effects by binding to E-prostanoid receptors (EP1-4). Although recent studies have shown that PGE2 induces cell differentiation in some neuronal cells such as mouse DRG neurons and sensory neuron-like ND7/23 cells, it is unclear whether PGE2 plays a role in differentiation of motor neurons. In the present study, we investigated the mechanism of PGE2-induced differentiation of motor neurons using NSC-34, a mouse motor neuron-like cell line. Exposure of undifferentiated NSC-34 cells to PGE2 and butaprost, an EP2-selective agonist, resulted in a reduction of MTT reduction activity without increase the number of propidium iodide-positive cells and in an increase in the number of neurite-bearing cells...
September 8, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28939129/salvianolic-acid-a-reverses-cisplatin-resistance-in-lung-cancer-a549-cells-by-targeting-c-met-and-attenuating-akt-mtor-pathway
#13
Xia-Li Tang, Li Yan, Ling Zhu, De-Min Jiao, Jun Chen, Qing-Yong Chen
Drug resistance is one of the leading causes of chemotherapy failure in non-small cell lung cancer (NSCLC) treatment. The purpose of this study was to investigate the role of c-met in human lung cancer cisplatin resistance cell line (A549/DDP) and the reversal mechanism of salvianolic acid A (SAA), a phenolic active compound extracted from Salvia miltiorrhiza. In this study, we found that A549/DDP cells exert up-regulation of c-met by activating the Akt/mTOR signaling pathway. We also show that SAA could increase the chemotherapeutic efficacy of cisplatin, suggesting a synergistic effect of SAA and cisplatin...
September 6, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28928055/electrophysiological-analyses-of-transgenic-mice-overexpressing-kcnj8-with-s422l-mutation-in-cardiomyocytes
#14
Yasuhiro Watanabe, Akio Matsumoto, Takashi Miki, Susumu Seino, Naohiko Anzai, Haruaki Nakaya
Genetic analysis of KCNJ8 has pointed a mutation (S422L) as a susceptible link to J wave syndrome (JWS). In vitro expression study indicated that the ATP-sensitive K(+) (KATP) channel with the S422L mutation has the gain-of-function with reduced sensitivity to ATP. However, the electrophysiological impact of KCNJ8 has not been elucidated in vivo. Transgenic mouse strains overexpressing KCNJ8 S422L variant (TGmt) or WT (TGWT) in cardiomyocytes have been created to investigate the influence of KCNJ8 in cardiomyocytes and the JWS-related feature of the S422L variant on the cardiac electrophysiology...
September 6, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28928053/development-of-correction-formula-for-field-potential-duration-of-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-sheets
#15
Hiroko Izumi-Nakaseko, Yasunari Kanda, Yuji Nakamura, Mihoko Hagiwara-Nagasawa, Takeshi Wada, Kentaro Ando, Atsuhiko T Naito, Yuko Sekino, Atsushi Sugiyama
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used in many studies to assess proarrhythmic risks of chemical compounds. In those studies, field potential durations (FPD) of hiPSC-CMs have been corrected by clinically used Fridericia's and/or Bazett's formulae, however, the rationale for the use of these formulae has not been well established. In the present study, we developed a correction formula for experiments using hiPSC-CMs. First, we analyzed the effect of beating rate on FPD in the hiPSC-CMs sheets with electrical stimuli and a HCN channel inhibitor zatebradine...
September 6, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28927781/function-of-38-variants-cyp2c9-polymorphism-on-ketamine-metabolism-in%C3%A2-vitro
#16
Xiang Zheng, Ping Fang, Su-Su Bao, Dan Lin, Jian-Ping Cai, Guo-Xin Hu
BACKGROUND: Cytochrome P450 proteins (CYP 450) is the most important enzyme system of drug phase I metabolism in liver. In previous reports, reduced efficiency or increased risk of adverse events can be affected by primary sequence mutation in CYP450. AIM: To investigate the effect of gene polymorphism on the metabolism of ketamine in vitro, including the new alleles: 2C9*58, *59 and *60. METHOD: Incubation system which was contained insect microsome, b5, NADPH and 1M PBS incubated 10 μM-1000 μM ketamine in 37 °C for 40 min concentration of norketamine was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry system (UPLC-MS/MS)...
September 1, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28928054/effect-of-the-antidiabetic-agent-pioglitazone-on-bone-metabolism-in-rats
#17
Junkichi Kanda, Nobuo Izumo, Yoshiko Kobayashi, Kenji Onodera, Taketoshi Shimakura, Noriaki Yamamoto, Hideaki E Takahashi, Hiroyuki Wakabayashi
Thiazolidinediones (TZDs) are synthetic peroxisome proliferator-activated receptor gamma (PPARγ) agonists used as therapy for type 2 diabetes. However, clinical studies reported that the therapeutic modulation of PPARγ activity using TZDs may induce negative effects on bone metabolism. This study aimed to evaluate the effect of the TZD pioglitazone on bone metabolism in rats. Male Wistar rats were treated orally with pioglitazone 5 or 20 mg/kg daily for 24 weeks. Bone strength was evaluated using a 3-point bending method, and bone histomorphometry was analyzed...
August 26, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28927780/effects-of-metformin-on-proliferation-and-apoptosis-of-human-megakaryoblastic-dami-and-meg-01-cells
#18
Xue Liang, Peiyan Kong, Jin Wang, Yulin Xu, Chunfang Gao, Guozhen Guo
Metformin has received increasing attention for its potential anticancer activity against certain human leukemia cells, but its effects on human megakaryoblastic cells are unclear. This study aimed to investigate the effects of metformin on proliferation and apoptosis of human megakaryoblastic cells (Dami and MEG-01) and the underlying molecular mechanisms. CCK8 assay was employed to measure cell proliferation. Flow cytometry was adopted to detect cell apoptosis. Western blot was further employed to measure apoptosis-related proteins...
August 23, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29083842/retraction-inhibition-of-arachidonic-acid-release-by-cytosolic-phospholipase-a2-is-involved-in-the-antiapoptotic-effect-of-fk506-and-cyclosporin-a-on-astrocytes-exposed-to-simulated-ischemia-in-vitro
#19
(no author information available yet)
No abstract text is available yet for this article.
October 19, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28923269/dpp-4-inhibition-protects-human-umbilical-vein-endothelial-cells-from-hypoxia-induced-vascular-barrier-impairment
#20
Naoko Hashimoto, Kento Ikuma, Yui Konno, Masanori Hirose, Hiroyuki Tadokoro, Hiroshi Hasegawa, Yoshio Kobayashi, Hiroyuki Takano
Dipeptidyl peptidase-4 (DPP-4) inhibitors are relatively new class of anti-diabetic drugs. Some protective effects of DPP-4 on cardiovascular disease have been described independently from glucose-lowering effect. However, the detailed mechanisms by which DPP-4 inhibitors exert on endothelial cells remain elusive. The purpose of this research was to determine the effects of DPP-4 inhibitor on endothelial barrier function. Human umbilical vein endothelial cells (HUVECs) were cultured and exposed to hypoxia in the presence or absence of Diprotin A, a DPP-4 inhibitor...
September 2017: Journal of Pharmacological Sciences
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