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Journal of Pharmacological Sciences

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https://www.readbyqxmd.com/read/28408165/alterations-in-protein-phosphorylation-in-the-amygdala-of-the-5xfamilial-alzheimer-s-disease-animal-model
#1
Eun-Jeong Yang, Usman Mahmood, Hyunju Kim, Moonseok Choi, Yunjung Choi, Jean-Pyo Lee, Moon-Jeong Chang, Hye-Sun Kim
Alzheimer's disease is the most common disease underlying dementia in humans. Two major neuropathological hallmarks of AD are neuritic plaques primarily composed of amyloid beta peptide and neurofibrillary tangles primarily composed of hyperphosphorylated tau. In addition to impaired memory function, AD patients often display neuropsychiatric symptoms and abnormal emotional states such as confusion, delusion, manic/depressive episodes and altered fear status. Brains from AD patients show atrophy of the amygdala which is involved in fear expression and emotional processing as well as hippocampal atrophy...
March 31, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28410966/vincristine-induced-peripheral-neuropathic-pain-and-expression-of-transient-receptor-potential-vanilloid-1-in-rat
#2
Terumasa Chiba, Yusuke Oka, Hiroya Sashida, Toshie Kanbe, Kenji Abe, Iku Utsunomiya, Kyoji Taguchi
The clinical anti-cancer efficacy of vincristine is limited by the development of dose-dependent peripheral neuropathy. Up-regulation of transient receptor potential vanilloid 1 (TRPV1) is correlated with peripheral neuropathy following anti-cancer drug treatment. To analyze the contribution of TRPV1 to the development of vincristine-induced mechanical allodynia/hyperalgesia, TRPV1 expression in the rat dorsal root ganglion (DRG) was analyzed after vincristine treatment. Mechanical allodynia/hyperalgesia was tested with von Frey filaments 14 days after intraperitoneal administration of 0...
March 30, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28410967/involvement-of-alpha-and-beta-adrenoceptors-in-the-automaticity-of-the-isolated-guinea-pig-pulmonary-vein-myocardium
#3
Masahiko Irie, Yayoi Tsuneoka, Mariko Shimobayashi, Nao Hasegawa, Yusuke Tanaka, Soh Mochizuki, Sho Ichige, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka
We examined the involvement of adrenoceptors in the automaticity of the pulmonary vein myocardium, which probably plays a crucial role in the generation of atrial fibrillation. The automatic activity of the myocardium in guinea pig pulmonary vein tissue preparations were monitored by contractile force or membrane potential measurement. In quiescent preparations, application of noradrenaline induced an automatic activity. The firing frequency was reduced by prazosin or atenolol. Methoxamine induced an automatic activity of low frequency, which was accelerated by further application of isoproterenol...
March 29, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28410965/permissive-role-of-reduced-inwardly-rectifying-potassium-current-density-in-the-automaticity-of-the-guinea-pig-pulmonary-vein-myocardium
#4
Yayoi Tsuneoka, Masahiko Irie, Yusuke Tanaka, Takahiko Sugimoto, Yuka Kobayashi, Taichi Kusakabe, Keisuke Kato, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka
The electrophysiological properties underlying the automaticity of the guinea pig pulmonary vein myocardium were studied. About 30% of the isolated pulmonary vein tissue preparations showed spontaneous electrical activity, as shown by glass microelectrode recordings from their myocardial layer. The remaining quiescent preparations had a resting membrane potential less negative than that in the left atria. Blockade of the acetylcholine activated potassium current (IK-ACh) by tertiapin induced a depolarizing shift of the resting membrane potential and automatic electrical activity in the pulmonary vein, but not in the atria...
March 28, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28391995/a-new-interaction-between-proximal-and-distal-c-terminus-of-cav1-2-channels
#5
Liting Lyu, Qinghua Gao, Jianjun Xu, Etsuko Minobe, Tong Zhu, Masaki Kameyama
Cardiac Cav1.2 channels, coupling membrane stimulation to intracellular Ca(2+) signaling, are regulated by multiple cytoplasmic factors, such as calmodulin (CaM), phosphorylation, Ca(2+), ATP and intramolecular fragments of the channel. The interaction between distal and proximal C-terminal regulatory domains (DCRD and PCRD) of Cav1.2 channel is suggested to inhibit the channel activity, while PKA-mediated phosphorylation facilitates Cav1.2 channel by releasing such an interaction. Here, we report that the interaction between the distal C-terminus (CT3) and the proximal C-terminus (CT1) are inhibited by CaM in a Ca(2+)-dependent manner...
March 25, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28363413/action-of-bacopa-monnieri-to-antagonize-cisplatin-induced-emesis-in-suncus-murinus-house-musk-shrew
#6
Ihsan Ullah, Fazal Subhan, Zengbing Lu, Sze Wa Chan, John A Rudd
Bacopa monnieri (BM, family Scrophulariaceae) is used in several traditional systems of medicine for the management of epilepsy, depression, neuropathic pain, sleep disorders and memory deficits. The present study investigated the potential of BM methanol (BM-MetFr) and BM n-butanol fractions (BM-ButFr) to reduce chemotherapy-induced emesis in Suncus murinus (house musk shrew). Cisplatin (30 mg/kg, i.p.) reliably induced retching and/or vomiting over a 2 day period. BM-MetFr (10-40 mg/kg, s.c.) and BM-ButFr (5-20 mg/kg, s...
March 12, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28391996/molecular-mechanisms-underlying-pimaric-acid-induced-modulation-of-voltage-gated-k-channels
#7
Kazuho Sakamoto, Yoshiaki Suzuki, Hisao Yamamura, Susumu Ohya, Katsuhiko Muraki, Yuji Imaizumi
Voltage-gated K(+) (KV) channels, which control firing and shape of action potentials in excitable cells, are supposed to be potential therapeutic targets in many types of diseases. Pimaric acid (PiMA) is a unique opener of large conductance Ca(2+)-activated K(+) channel. Here, we report that PiMA modulates recombinant rodent KV channel activity. The enhancement was significant at low potentials (<0 mV) but not at more positive potentials. Application of PiMA significantly shifted the voltage-activation relationships (V1/2) of rodent KV1...
March 8, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28330759/amiodarone-reduces-depolarization-evoked-glutamate-release-from-hippocampual-synaptosomes
#8
Chia Yu Chang, Chi Feng Hung, Shu Kuei Huang, Jinn Rung Kuo, Su Jane Wang
Decreased brain glutamate level has emerged as a new therapeutic approach for epilepsy. This study investigated the effect and mechanism of amiodarone, an anti-arrhythmic drug with antiepileptic activity, on glutamate release in the rat hippocampus. In a synaptosomal preparation, amiodarone reduced 4-aminopyridine-evoked Ca(2+)-dependent glutamate release and cytosolic Ca(2+) concentration elevation. Amiodarone did not affect the 4-aminopyridine-evoked depolarization of the synaptosomal membrane potential or the Na(+) channel activator veratridine-evoked glutamate release, indicating that the amiodarone-mediated inhibition of glutamate release is not caused by a decrease in synaptosomal excitability...
March 8, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28325557/effects-of-new-antiarrhythmic-agent-ss-68-on-excitation-conduction-electrical-activity-in-purkinje-fibers-and-pulmonary-veins-assessment-of-safety-and-side-effects-risk
#9
Saida K Bogus, Vladislav S Kuzmin, Denis V Abramochkin, Konstantin F Suzdalev, Pavel A Galenko-Yaroshevsky
The compound SS-68 has been selected among numerous new derivatives of indole and demonstrated antiarrhythmic effects in animal models. The present study concerns several aspects of SS-68 safety and efficacy as a potential antiarrhythmic drug. The first estimation of atrioventricular conduction in mammalian heart under SS-68 has been carried out; effects of SS-68 in Purkinje fibers and myocardium of pulmonary veins have been investigated. The drug weakly affects cardiac atrioventricular conduction: only high concentrations of SS-68 (≥10 μmol/L) significantly decrease this parameter...
March 2, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28318829/toll-like-receptor-4-inhibitor-protects-against-retinal-ganglion-cell-damage-induced-by-optic-nerve-crush-in-mice
#10
Yukimichi Nakano, Masamitsu Shimazawa, Kazuki Ojino, Hiroshi Izawa, Hiroto Takeuchi, Yuki Inoue, Kazuhiro Tsuruma, Hideaki Hara
Toll-like receptor 4 (TLR4) plays key roles in innate immune responses and inflammatory reactions. TAK-242 (resatorvid) is a small-molecule cyclohexene derivative that selectively inhibits TLR4 signaling pathways and suppresses inflammatory reactions. Here we investigated the protective effects of TAK-242 against optic nerve crush (ONC) which induces axonal injury like glaucoma in mice. TAK-242 was injected intravitreally immediately after ONC. The effect of TAK-242 was evaluated by measuring the number of fluorogold-labeled retinal ganglion cells (RGCs) at 10 days after ONC...
March 2, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28302446/electrophysiological-evidence-of-increased-glycine-receptor-mediated-phasic-and-tonic-inhibition-by-blockade-of-glycine-transporters-in-spinal-superficial-dorsal-horn-neurons-of-adult-mice
#11
Misa Oyama, Seiya Kuraoka, Shun Watanabe, Takashi Iwai, Mitsuo Tanabe
To understand the synaptic and/or extrasynaptic mechanisms underlying pain relief by blockade of glycine transporter subtypes GlyT1 and GlyT2, whole-cell recordings were made from dorsal horn neurons in spinal slices from adult mice, and the effects of NFPS and ALX-1393, selective GlyT1 and GlyT2 inhibitors, respectively, on phasic evoked or miniature glycinergic inhibitory postsynaptic currents (eIPSCs or mIPSCs) were examined. NFPS and ALX-1393 prolonged the decay phase of eIPSCs without affecting their amplitude...
February 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28314697/demeanor-of-rivaroxaban-in-activated-inactivated-fxa
#12
Kaname Seki, Yosuke Mizuno, Toku Sakashita, Shintaro Nakano, Jun Tanno, Yasushi Okazaki, Toshihiro Muramatsu, Shigeyuki Nishimura, Takaaki Senbonmatsu
Activated factor X (FXa) plays an important role in thrombin generation and inflammation. Factor X is not converted constitutively to FXa, but only after intrinsic clotting factors are activated and/or cellular injury occurs. Although rivaroxaban is one of direct FXa inhibitors, its function in the inactivated coagulation cascade is unclear. In human umbilical vein endothelial cells that natively express protease-activated receptor-1 and -2, high dose rivaroxaban did not alter gene transcripts including pro-inflammatory genes in DNA microarray...
February 24, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28302448/aconitine-a-potential-novel-treatment-for-systemic-lupus-erythematosus
#13
Xiaodong Li, Liwei Gu, Lan Yang, Dong Zhang, Jianying Shen
BACKGROUND: Aconitum plants have been widely used in China for thousands of years. Recent evidences indicate that aconitine, the main active ingredient of Aconitum, has immunomodulatory properties that might be useful for treating autoimmune diseases, such as rheumatoid arthritis. In this study, we conducted a pilot study to explore the effect and mechanisms of aconitine on the treatment of systemic lupus erythematosus. METHODS: A pristane-induced murine model was used...
February 24, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28286019/methotrexate-causes-acute-hyperplasia-of-enterochromaffin-cells-containing-substance-p-in-the-intestinal-mucosa-of-rats
#14
Takuji Machida, Yuho Takano, Kenji Iizuka, Maiko Machida, Masahiko Hirafuji
This study aimed to investigate the acute and chronic effect of methotrexate on the intestinal substance P metabolism after a single administration to rats. Methotrexate caused a significant increase in the number of substance P-containing cells in the ileal mucosa both at 24 and 96 h. Most of enterochromaffin cells expressing l-tryptophan hydroxylase contained substance P. The expression of Tac1 mRNA was increased by methotrexate at 24 h, but not at 96 h. Thus, methotrexate causes acute hyperplasia of enterochromaffin cells in the intestinal mucosa of rats with a transient increase in the production of substance P...
February 22, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28325558/l-citrulline-ameliorates-cerebral-blood-flow-during-cortical-spreading-depression-in-rats-involvement-of-nitric-oxide-and-prostanoids-mediated-pathway
#15
Yuki Kurauchi, Koichi Mokudai, Asami Mori, Kenji Sakamoto, Tsutomu Nakahara, Masahiko Morita, Ayako Kamimura, Kunio Ishii
l-Citrulline is a potent precursor of l-arginine, and exerts beneficial effect on cardiovascular system via nitric oxide (NO) production. Migraine is one of the most popular neurovascular disorder, and imbalance of cerebral blood flow (CBF) observed in cortical spreading depression (CSD) contributes to the mechanism of migraine aura. Here, we investigated the effect of l-citrulline on cardiovascular changes to KCl-induced CSD. in rats. Intravenous injection of l-citrulline prevented the decrease in CBF, monitored by laser Doppler flowmetry, without affecting mean arterial pressure and heart rate during CSD...
February 17, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28302447/dcebio-facilitates-myogenic-differentiation-via-intermediate-conductance-ca-2-activated-k-channel-activation-in-c2c12-myoblasts
#16
Shoko Tanaka, Yuko Ono, Kazuho Sakamoto
Membrane hyperpolarization is suggested to be a trigger for skeletal muscle differentiation. We investigated whether DCEBIO, an opener of the small/intermediate conductance Ca(2+) activated K(+) (SKCa/IKCa) channels, increase myogenic differentiation in C2C12 skeletal myoblasts. DCEBIO significantly increased myotube formation, protein expression level of myosin heavy chain II, and mRNA expression level of myogenin in C2C12 myoblasts cultured in differentiation medium. DCEBIO induced myotube formation and hyperpolarization were reduced by the IKCa channel blocker TRAM-34, but not by the SKCa channel blocker apamin...
February 17, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28279595/effect-of-a-dosing-time-on-quetiapine-induced-acute-hyperglycemia-in-mice
#17
Snehal Kapse, Hitoshi Ando, Yuki Fujiwara, Chisato Suzuki, Kentaro Ushijima, Hiroko Kitamura, Keiko Hosohata, Kazuhiko Kotani, Shigeki Shimba, Akio Fujimura
Although rare, second-generation antipsychotic drugs cause severe hyperglycemia within several days after the initiation of therapy. Because glucose tolerance exhibits circadian rhythmicity, we evaluated an effect of a dosing-time on quetiapine-induced acute hyperglycemia in mice. A single intraperitoneal dose of quetiapine dosing-time-independently induced insulin resistance in fasted C57BL/6J mice. However, acute hyperglycemic effect was detected only after dosing of the drug at the beginning of an active phase...
February 17, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28259560/4-chlorophenylguanidine-is-an-asic3-agonist-and-positive-allosteric-modulator
#18
Amruta S Agharkar, Eric B Gonzales
Acid-sensing ion channels (ASICs) are proton-sensitive sodium channels that open in response to lowered extracellular pH and are expressed in the central and peripheral nervous systems. The ASIC3 subtype is found primarily in the periphery where the channel mediates pain signals caused by ischemia and inflammation. Here, we provide identify 4-chlorophenylguanidine (4-CPG) as an ASIC3 positive allosteric modulator and newest member of the growing group of guanidine modulators of ASICs. Furthermore, the 4-CPG reversed the effects of ASIC3 desensitization...
February 17, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28366492/effects-of-k-877-a-novel-selective-ppar%C3%AE-modulator-on-small-intestine-contribute-to-the-amelioration-of-hyperlipidemia-in-low-density-lipoprotein-receptor-knockout-mice
#19
Kenta Takei, Yoshimi Nakagawa, Yunong Wang, Song-Iee Han, Aoi Satoh, Motohiro Sekiya, Takashi Matsuzaka, Hitoshi Shimano
Peroxisome proliferator-activated receptor α (PPARα) is a well-known therapeutic target for treating hyperlipidemia. K-877 is a novel selective PPARα modulator (SPPARMα) that enhances PPARα transcriptional activity with high selectivity and potency, resulting in reduced plasma lipid levels. This study aimed to evaluate the effects of K-877 on hyperlipidemia in low-density lipoprotein receptor knockout (Ldlr(-/-)) mice, a mouse model of atherosclerosis. We revealed that K-877 administration significantly decreased plasma triglyceride (TG) and total cholesterol (TC) levels and increased plasma high-density lipoprotein cholesterol (HDL-C) levels in Ldlr(-/-) mice...
February 11, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28258822/intra-articular-lentivirus-mediated-gene-therapy-targeting-cracm1-for-the-treatment-of-collagen-induced-arthritis
#20
Shuang Liu, Takeshi Kiyoi, Erika Takemasa, Kazutaka Maeyama
Abnormal store-operated calcium uptake has been observed in peripheral T lymphocytes of rheumatoid arthritis (RA) patients, and sustained intracellular calcium signalling is known to mediate the functions of many types of immune cells. Thus, it is hypothesized that regulating calcium entry through CRACM1 (the pore-forming subunit of calcium release-activated calcium (CRAC) channels; also known as ORAI1) may be beneficial for the management of RA. Localized CRACM1 knockdown in the joints and draining lymph nodes (DLNs) of mice with collagen-induced arthritis (CIA) was achieved via lentiviral-based delivery of shRNA targeting mouse CRACM1...
February 11, 2017: Journal of Pharmacological Sciences
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