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Journal of Pharmacological Sciences

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https://www.readbyqxmd.com/read/28209485/effects-of-clozapine-on-adipokine-secretions-productions-and-lipid-droplets-in-3t3-l1-adipocytes
#1
Tomomi Tsubai, Akira Yoshimi, Yoji Hamada, Makoto Nakao, Hiroshi Arima, Yutaka Oiso, Yukihiro Noda
Clozapine, a second-generation antipsychotic (SGA), is a cause of side effects related to metabolic syndrome. The participation of serotonin 5-HT2C and histamine H1 receptors in the central nervous system has been reported as a mechanism of the weight gain caused by clozapine. In the present study, we investigated the direct pharmacological action of clozapine on the 3T3-L1 adipocytes and compared it to that of blonanserin, an SGA with low affinity for both receptors. Short-term exposure to clozapine decreased secretion and mRNA expression of leptin...
January 28, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28089228/intraplantar-injection-of-sialidase-reduces-mechanical-allodynia-during-inflammatory-pain
#2
Shun Watanabe, Takashi Iwai, Mitsuo Tanabe
Sialic acids are highly charged glycoresidues that are attached to glycoproteins or glycosphingolipids, and they are associated with various biological functions. Gangliosides, sialic acid-containing glycosphingolipids, are abundant in neural tissues and play important roles in the nervous system. Previous studies revealed that peripheral gangliosides are involved in nociceptive behavior and hyperalgesia. These observations prompted us to determine whether the sialic acid-cleaving enzyme sialidase affects pain signaling...
January 3, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28081948/high-glucose-induces-n-linked-glycosylation-mediated-functional-upregulation-and-overexpression-of-cav3-2-t-type-calcium-channels-in-neuroendocrine-like-differentiated-human-prostate-cancer-cells
#3
Kazuki Fukami, Erina Asano, Mai Ueda, Fumiko Sekiguchi, Shigeru Yoshida, Atsufumi Kawabata
Given that Cav3.2 T-type Ca(2+) channels were functionally regulated by asparagine (N)-linked glycosylation, we examined effects of high glucose on the function of Cav3.2, known to regulate secretory function, in neuroendocrine-like differentiated prostate cancer LNCaP cells. High glucose accelerated the increased channel function and overexpression of Cav3.2 during neuroendocrine differentiation, the former prevented by enzymatic inhibition of N-glycosylation and cleavage of N-glycans. Hyperglycemia thus appears to induce N-linked glycosylation-mediated functional upregulation and overexpression of Cav3...
January 3, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28081947/the-effects-of-dpp-4-inhibitor-on-hypoxia-induced-apoptosis-in-human-umbilical-vein-endothelial-cells
#4
Akari Nagamine, Hiroshi Hasegawa, Naoko Hashimoto, Tomoko Yamada-Inagawa, Masanori Hirose, Yuka Kobara, Hiroyuki Tadokoro, Yoshio Kobayashi, Hiroyuki Takano
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral hypoglycemic agents for patients with type 2 diabetes mellitus and have potential antiatherosclerotic properties. Meanwhile, it is unclear how DPP-4 inhibitors have protective effects on atherosclerosis. Our aim was to determine the effects and its mechanisms of DPP-4 inhibitors on cultured endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured in hypoxic condition. To evaluate the protective effects of DPP-4 inhibitor on HUVECs, DPP-4 inhibitor was added in the cell culture medium and the cell viability was assessed by TUNEL assay...
January 3, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28087150/apelin-protects-against-nmda-induced-retinal-neuronal-death-via-an-apj-receptor-by-activating-akt-and-erk1-2-and-suppressing-tnf-%C3%AE-expression-in-mice
#5
Yuki Ishimaru, Akihide Sumino, Daiki Kajioka, Fumiya Shibagaki, Akiko Yamamuro, Yasuhiro Yoshioka, Sadaaki Maeda
Glutamate excitotoxicity mediated by N-methyl-d-aspartate (NMDA) receptors is an important cause of retinal ganglion cell death in glaucoma. To elucidate whether apelin protects against retinal neuronal cell death, we examined protective effects of exogenous and endogenous apelin on neuronal cell death induced by intravitreal injection of NMDA in the retinas of mice. An intravitreal injection of NMDA induced neuronal cell death in both the retinal ganglion cell layer and inner nuclear layer, and reduced the amplitudes of scotopic threshold response (STR) in electroretinography studies...
December 24, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28117214/a-novel-jak-inhibitor-peficitinib-demonstrates-potent-efficacy-in-a-rat-adjuvant-induced-arthritis-model
#6
Misato Ito, Shunji Yamazaki, Kaoru Yamagami, Masako Kuno, Yoshiaki Morita, Kenji Okuma, Koji Nakamura, Noboru Chida, Masamichi Inami, Takayuki Inoue, Shohei Shirakami, Yasuyuki Higashi
The Janus kinase (JAK) family of tyrosine kinases is associated with various cytokine receptors. JAK1 and JAK3 play particularly important roles in the immune response, and their inhibition is expected to provide targeted immune modulation. Several oral JAK inhibitors have recently been developed for treating autoimmune diseases, including rheumatoid arthritis (RA). Here, we investigated the pharmacological effects of peficitinib (formerly known as ASP015K), a novel, chemically synthesized JAK inhibitor. We found that peficitinib inhibited JAK1 and JAK3 with 50% inhibitory concentrations of 3...
December 23, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28057412/peripheral-administration-of-interleukin-13-reverses-inflammatory-macrophage-and-tactile-allodynia-in-mice-with-partial-sciatic-nerve-ligation
#7
Norikazu Kiguchi, Haruka Sakaguchi, Yui Kadowaki, Fumihiro Saika, Yohji Fukazawa, Shinsuke Matsuzaki, Shiroh Kishioka
Inflammatory macrophages play a fundamental role in neuropathic pain. In this study, we demonstrate the effects of peripheral interleukin-13 (IL-13) on neuropathic pain after partial sciatic nerve (SCN) ligation (PSL) in mice. IL-13 receptor α1 was upregulated in accumulating macrophages in the injured SCN after PSL. Treatment with IL-13 reduced inflammatory macrophage-dominant molecules and increased suppressive macrophage-dominant molecules in cultured lipopolysaccharide-stimulated peritoneal macrophages and ex vivo SCN subjected to PSL...
December 23, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28034513/suppression-of-the-acute-upregulation-of-phosphorylated-extracellular-regulated-kinase-in-ventral-tegmental-area-by-a-%C3%AE-opioid-receptor-agonist-is-related-to-resistance-to-rewarding-effects-in-a-mouse-model-of-bone-cancer
#8
Atsushi Nakamura, Hiroko Ono, Azusa Ando, Mikie Hinata, Kazuki Niidome, Shigeki Omachi, Gaku Sakaguchi, Shunji Shinohara
We investigated the mechanisms underlying the suppression of the rewarding effects of opioids using the femur bone cancer (FBC) mouse model. The rewarding and antinociceptive effects of subcutaneously administered morphine and oxycodone in the FBC model mice were assessed using the conditioned place preference test and the von-Frey test. In FBC mice, antinociceptive doses of morphine (30 mg/kg) and oxycodone (5 mg/kg) did not produce the rewarding effects but excessive doses of morphine (300 mg/kg) and oxycodone (100 mg/kg) did...
December 8, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28007462/celecoxib-inhibits-osteoblast-maturation-by-suppressing-the-expression-of-wnt-target-genes
#9
Akihiro Nagano, Masaki Arioka, Fumi Takahashi-Yanaga, Etsuko Matsuzaki, Toshiyuki Sasaguri
Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to impair bone healing. We previously reported that in colon cancer cells, celecoxib, a COX-2-selective NSAID, inhibited the canonical Wnt/β-catenin signaling pathway. Since this pathway also plays an important role in osteoblast growth and differentiation, we examined the effect of celecoxib on maturation of osteoblast-like cell line MC3T3-E1. Celecoxib induced degradation of transcription factor 7-like 2, a key transcription factor of the canonical Wnt pathway...
December 1, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27979701/gpr40-ffar1-deficient-mice-increase-noradrenaline-levels-in-the-brain-and-exhibit-abnormal-behavior
#10
Fuka Aizawa, Takashi Nishinaka, Takuya Yamashita, Kazuo Nakamoto, Takashi Kurihara, Akira Hirasawa, Fumiyo Kasuya, Atsuro Miyata, Shogo Tokuyama
The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice...
December 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27919568/all-trans-retinoic-acid-suppresses-the-adhering-ability-of-arpe-19-cells-via-mitogen-activated-protein-kinase-and-focal-adhesion-kinase
#11
Yo-Chen Chang, Yuh-Shin Chang, Ming-Chu Hsieh, Horng-Jiun Wu, Meng-Hsien Wu, Chia-Wei Lin, Wen-Chuan Wu, Ying-Hsien Kao
This study investigated the signaling mechanism underlying the anti-adhesive effect of all-trans retinoic acid (ATRA) on retinal pigment epithelial ARPE-19 cells. Adhesion kinetics with or without ATRA treatment were profiled by adhesion assay. Surface coating with type IV collagen, fibronectin, laminin, but not type I collagen, significantly enhanced adhesion and spreading of ARPE-19 cells, while ATRA at subtoxic doses (ranging from 10(-7) to 10(-6) M) profoundly suppressed the extracellular matrix-enhanced adhesion ability...
December 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27889414/changes-in-glucose-induced-plasma-active-glucagon-like-peptide-1-levels-by-co-administration-of-sodium-glucose-cotransporter-inhibitors-with-dipeptidyl-peptidase-4-inhibitors-in-rodents
#12
Takahiro Oguma, Chiaki Kuriyama, Keiko Nakayama, Yasuaki Matsushita, Kumiko Hikida, Minoru Tsuda-Tsukimoto, Akira Saito, Kenji Arakawa, Kiichiro Ueta, Masabumi Minami, Masaharu Shiotani
We investigated whether structurally different sodium-glucose cotransporter (SGLT) 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4) inhibitors, could enhance glucagon-like peptide-1 (GLP-1) secretion during oral glucose tolerance tests (OGTTs) in rodents. Three different SGLT inhibitors-1-(β-d-Glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene (GTB), TA-1887, and canagliflozin-were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1) elevation and suppressed glucose excursions in both normal and diabetic rodents...
December 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27884451/cholesterol-lowering-pattern-affects-the-progression-of-atherosclerosis-in-apolipoprotein-e-deficient-mice
#13
Yusuke Masuda, Shinji Yamaguchi, Tomohiro Nishizawa
Although the importance of LDL cholesterol lowering is widely recognized, the impact of the cholesterol-lowering pattern on the atherosclerosis remains unclear. Here, we used cholestyramine in apolipoprotein E deficient mice in two different regimens to induce a see-saw shaped or a sustained cholesterol reduction, with the trough of cholesterol comparable. After 12 weeks-treatment, a sustained cholesterol reduction exhibited a smaller atherosclerotic area. Moreover, we observed a correlation between the area under the curve of plasma cholesterol and the atherosclerotic area...
December 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27581589/cellular-function-and-signaling-pathways-of-vascular-smooth-muscle-cells-modulated-by-sphingosine-1-phosphate
#14
REVIEW
Takuji Machida, Ryosuke Matamura, Kenji Iizuka, Masahiko Hirafuji
Sphingosine 1-phosphate (S1P) plays important roles in cardiovascular pathophysiology. S1P1 and/or S1P3, rather than S1P2 receptors, seem to be predominantly expressed in vascular endothelial cells, while S1P2 and/or S1P3, rather than S1P1 receptors, seem to be predominantly expressed in vascular smooth muscle cells (VSMCs). S1P has multiple actions, such as proliferation, inhibition or stimulation of migration, and vasoconstriction or release of vasoactive mediators. S1P induces an increase of the intracellular Ca(2+) concentration in many cell types, including VSMCs...
December 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27245553/the-effects-of-rabeprazole-on-metformin-pharmacokinetics-and-pharmacodynamics-in-chinese-healthy-volunteers
#15
Guojing Liu, Jiagen Wen, Dong Guo, Zhenmin Wang, Xiaolei Hu, Jie Tang, Zhaoqian Liu, Honghao Zhou, Wei Zhang
The aim was to investigate the role of rabeprazole on the pharmacokinetics (PK) and pharmacodynamics (PD) of metformin. The in vitro inhibition assays on metformin transport were carried out and showed that the half maximal inhibitory concentration (IC50) of rabeprazole on OCT2-mediated metformin transport was 26.0 μM, whereas the IC50 on MATE1-mediated metformin transport inhibition was 4.6 μM. Fifteen healthy Chinese male volunteers were enrolled and given two different doses of metformin plus the co-administration of placebo or rabeprazole...
December 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27107824/atrial-selective-block-of-sodium-channels-by-acehytisine-in-rabbit-myocardium
#16
Xinrong Fan, Chao Wang, Na Wang, Xianhong Ou, Hanxiong Liu, Yan Yang, Xitong Dang, Xiaorong Zeng, Lin Cai
Acehytisine, a multi-ion channel blocker, can markedly inhibit INa, ICa, IKur, If at various concentrations and effectively terminate and prevent atrial fibrillation (AF) in patients and animal models, but the molecular mechanism underlying its blockage remains elusive. In this study, we investigated the effects of acehytisine on action potentials and sodium channels of atrial and ventricular myocytes isolated from rabbit, using whole-cell recording system. We found that acehytisine exerted stronger blocking effects on sodium channels in atria than in ventricles, especially at depolarization (IC50: 48...
December 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27107823/inhibition-of-extracellular-matrix-production-and-remodeling-by-doxycycline-in-smooth-muscle-cells
#17
Rogelio Palomino-Morales, Carolina Torres, Sonia Perales, Ana Linares, Maria Jose Alejandre
Alterations in the extracellular matrix (ECM) production and remodeling of smooth muscle cells (SMCs) have been implicated in processes related to the differentiation in atherosclerosis. Due to the anti-atherosclerotic properties of the tetracyclines, we aimed to investigate whether cholesterol supplementation changes the effect of doxycycline over the ECM proteins synthesis and whether isoprenylated proteins and Rho A protein activation are affected. SMC primary culture isolated from chicks exposed to atherogenic factors in vivo (a cholesterol-rich diet, SMC-Ch), comparing it with control cultures isolated after a standard diet (SMC-C)...
December 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27103329/suramin-inhibits-antibody-binding-to-cell-surface-antigens-and-disrupts-complement-mediated-mesangial-cell-lysis
#18
Honglan Piao, Yuan Chi, Xiling Zhang, Zhen Zhang, Kun Gao, Manabu Niimi, Manabu Kamiyama, Jinming Zhang, Masayuki Takeda, Jian Yao
Suramin inhibits immune responses and protects cells against inflammatory cell injury. However, little is known about its mechanisms. Using an in vitro model of glomerular mesangial cell (MC) lysis induced by antibodies plus complement, we investigated the potential protective effects and mechanisms of suramin on immunologic cell injury. Exposure of rat MCs to anti-Thy-1 antibody plus complement or anti-MC rabbit serum caused complement-dependent cell lysis, which was blocked by suramin and its structural analogue NF023 and NF049, but not by PPADS, an antagonist of purinergic receptors...
December 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27865709/defective-splicing-of-the-background-k-channel-k2p5-1-by-the-pre-mrna-splicing-inhibitor-pladienolide-b-in-lectin-activated-mouse-splenic-cd4-t-cells
#19
Kazutaka Tagishi, Ayaka Shimizu, Kyoko Endo, Hiroaki Kito, Satomi Niwa, Masanori Fujii, Susumu Ohya
The two-pore domain K(+) channel K2P5.1 has been implicated in the pathogenesis of autoimmune diseases. We investigated the changes in K2P5.1 activity caused by a defect in normal pre-mRNA splicing in concanavalin A-activated mouse splenic CD4(+) T cells. The pre-mRNA splicing inhibitor, pladienolide B (1 μM) markedly decreased full-length K2P5.1 transcription in activated CD4(+) T cells, resulting in the disappearance of K2P5.1 activity and an imbalance in Th17 and Treg cytokines. These results suggest that the defect in K2P5...
November 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27842970/dentin-hypersensitivity-like-tooth-pain-seen-in-patients-receiving-steroid-therapy-an-exploratory-study
#20
Noriaki Shoji, Yu Endo, Masahiro Iikubo, Tomonori Ishii, Hideo Harigae, Jun Aida, Maya Sakamoto, Takashi Sasano
To ascertain whether steroid therapy evokes dentin hypersensitivity (DH)-like tooth pain, we performed a study based on compelling evidence from patients receiving steroid therapy. An exploratory study was conducted using a questionnaire for 220 patients prescribed steroids who attended the Department of Hematology and Rheumatology of Tohoku University Hospital. Group comparisons between patients with and without steroid pulse therapy were analysed by statistical means. In this study, any DH-like tooth pain that commenced subsequent to steroid treatment was defined as steroid-derived (SD) tooth pain...
November 2016: Journal of Pharmacological Sciences
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