Editorial Board
Publication date: August 2019Source: Journal of Pharmacological Sciences, Volume 140, Issue 4Author(s): (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - October 18, 2019 Category: Drugs & Pharmacology Source Type: research

Retrograde signaling via axonal transport through signaling endosomes
Publication date: Available online 17 October 2019Source: Journal of Pharmacological SciencesAuthor(s): Naoya YamashitaAbstractNeurons extend axons far from cell bodies, and retrograde communications from distal axons to cell bodies and/or dendrites play critical roles in the development and maintenance of neuronal circuits. In neurotrophin signaling, the retrograde axonal transport of endosomes containing active ligand-receptor complexes from distal axons to somatodendrite compartments mediates retrograde signaling. However, the generality and specificity of these endosome-based transportations called “signaling end...
Source: Journal of Pharmacological Sciences - October 17, 2019 Category: Drugs & Pharmacology Source Type: research

A novel free radical scavenger, NSP-116, ameliorated the brain injury in both ischemic and hemorrhagic stroke models
Publication date: Available online 15 October 2019Source: Journal of Pharmacological SciencesAuthor(s): Takahiko Imai, Sena Iwata, Daisuke Miyo, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki HaraAbstractReperfusion injury is a serious problem in ischemic stroke therapy, which leads to neuronal damage and intracranial hemorrhage (ICH). A novel free radical scavenger, NSP-116, has anti-oxidative effect and may ameliorate reperfusion injury. The purpose of this study was to investigate the effects of NSP-116 on both ischemic and hemorrhagic stroke models.First, we assessed whether NSP-116 has protective effects in vitro. Pr...
Source: Journal of Pharmacological Sciences - October 17, 2019 Category: Drugs & Pharmacology Source Type: research

Role of Rac1 in augmented endothelin-1-induced bronchial contraction in airway hyperresponsive mice
Publication date: Available online 10 October 2019Source: Journal of Pharmacological SciencesAuthor(s): Yuki Kai, Risako Kon, Nobutomo Ikarashi, Yoshihiko Chiba, Junzo Kamei, Hiroyasu SakaiAbstractIt has recently been exhibited that Rac1 expression is increased in the bronchial tissue of a murine model with repeated antigen-challenged airway hyperresponsiveness (AHR). In the present study, the role of Rac1 in endothelin-1 (ET-1)-induced bronchial contraction and myosin light chain (MLC) phosphorylation was examined in AHR mice. Enhanced reactions in AHR mice were prevented by the Rac1 inhibitor NSC23766. These findings sug...
Source: Journal of Pharmacological Sciences - October 11, 2019 Category: Drugs & Pharmacology Source Type: research

A novel rat model of contrast-induced nephropathy based on dehydration
ConclusionsA novel CIN rat model based on dehydration and iohexol exposure was established and validated to assist in understanding and preventing CIN. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - September 29, 2019 Category: Drugs & Pharmacology Source Type: research

Puerarin prevents progression of experimental hypoxia-induced pulmonary hypertension via inhibition of autophagy
In this study, we explored the effects of puerarin in a hypoxic pulmonary hypertension (PH) rat model using immunohistochemistry, and morphometric analyses of right ventricle. In addition, cell counting kit 8 assay, western blotting and flow cytometry were employed to test cell proliferation in PASMCs, and then autophagy was tested with mRFP-GFP-LC3 fluorescence microscopy and western blot. We found that puerarin could alleviate hypoxia-induced PH in rats and improved pulmonary histopathology, and also reduced the expression of autophagy markers in vivo and in vitro. Moreover, puerarin also ameliorated hypoxia-induced PASM...
Source: Journal of Pharmacological Sciences - September 29, 2019 Category: Drugs & Pharmacology Source Type: research

Therapeutic targeting of mitochondrial ROS ameliorates murine model of volume overload cardiomyopathy
Publication date: Available online 28 September 2019Source: Journal of Pharmacological SciencesAuthor(s): Kenichi Okamura, Yu Nakagama, Norihiko Takeda, Katsura Soma, Tatsuyuki Sato, Takayuki Isagawa, Yasutoshi Kido, Masaya Sakamoto, Ichiro Manabe, Yasutaka Hirata, Issei Komuro, Minoru OnoAbstractConcomitant heart failure is associated with poor clinical outcome in dialysis patients. The arteriovenous shunt, created as vascular access for hemodialysis, increases ventricular volume-overload, predisposing patients to developing cardiac dysfunction. The integral function of mitochondrial respiration is critically important fo...
Source: Journal of Pharmacological Sciences - September 29, 2019 Category: Drugs & Pharmacology Source Type: research

P53-Induced Reduction of Lipid Peroxidation Supports Brain Microvascular Endothelium Integrity
In conclusion, P53 supports BBB integrity, at least in part, by reducing lipid peroxidation. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - September 29, 2019 Category: Drugs & Pharmacology Source Type: research

Activation of adenosine A2A but not A2B receptors is involved in uridine adenosine tetraphosphate-induced porcine coronary smooth muscle relaxation
Publication date: Available online 27 September 2019Source: Journal of Pharmacological SciencesAuthor(s): Changyan Sun, Tong Jiao, Daphne Merkus, Dirk J. Duncker, S. Jamal Mustafa, Zhichao ZhouAbstractActivation of both adenosine A2A and A2B receptors (A2BR) contributes to coronary vasodilation. We previously demonstrated that uridine adenosine tetraphosphate (Up4A) is a novel vasodilator in the porcine coronary microcirculation, acting mainly on A2AR in smooth muscle cells (SMC). We further investigated whether activation of A2BR is involved in Up4A-mediated coronary SMC relaxation. Both A2AR and A2BR may stimulate H2O2 p...
Source: Journal of Pharmacological Sciences - September 28, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: July 2019Source: Journal of Pharmacological Sciences, Volume 140, Issue 3Author(s): (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - September 25, 2019 Category: Drugs & Pharmacology Source Type: research

Pharmacological β-adrenoceptor blockade can augment torsadogenic action of IKr inhibitor: Comparison of proarrhythmic effects of d-sotalol and dl-sotalol in the chronic atrioventricular block dogs
Publication date: Available online 24 September 2019Source: Journal of Pharmacological SciencesAuthor(s): Ai Goto, Mihoko Hagiwara-Nagasawa, Koki Chiba, Ryuichi Kambayashi, Yoshio Nunoi, Hiroko Izumi-Nakaseko, Akio Matsumoto, Yasunari Kanda, Atsushi SugiyamaAbstractInformation is still limited whether β-blockade may augment or attenuate the onset of torsade de pointes in patients with IKr inhibitor-induced labile repolarization process. We compared the proarrhythmic effects of d-sotalol with those of dl-sotalol using the chronic atrioventricular block dogs, since d- and l-isomers share a similar blocking action on IKr...
Source: Journal of Pharmacological Sciences - September 25, 2019 Category: Drugs & Pharmacology Source Type: research

Overexpression of microRNA-21 mediates Ang II-induced renal fibrosis by activating the TGF-β1/Smad3 pathway via suppressing PPARα
Publication date: Available online 23 September 2019Source: Journal of Pharmacological SciencesAuthor(s): Huiyan Lv, Xin Li, Qi Wu, Lirong HaoAbstractAngiotensin II (Ang II) is an important profibrotic factor, and the tumor-promoting microRNA miR-21 was recently linked to fibrotic disorders. We aimed to investigate whether and how miR-21 mediates Ang II-induced renal fibrosis. In renal tubular epithelial cells, Ang II upregulated miR-21 and fibrosis-related indicators but decreased PPARα expression. miR-21 overexpression promoted PPARα downregulation, activated the TGF-β1/Smad3 pathway and induced fibrogen...
Source: Journal of Pharmacological Sciences - September 25, 2019 Category: Drugs & Pharmacology Source Type: research

Involvement of l-Lactate in Hippocampal Dysfunction of Type I Diabetes
Publication date: Available online 13 September 2019Source: Journal of Pharmacological SciencesAuthor(s): Riho Kobayashi, Junya Maruoka, Hiroaki Norimoto, Yuji Ikegaya, Kazuhiko Kume, Masahiro OhsawaAbstractHippocampal neurons play a crucial role in memory formation. Accumulating evidence raises the possibility that hippocampal sharp-wave ripples (SW-Rs) are involved in memory consolidation. Here, we examined in an animal model of diabetes and found the amplitude of SW-Rs in diabetic mice were smaller than control group and were rescued by acute application of L-lactate, a major neural energy source. The cognitive impairme...
Source: Journal of Pharmacological Sciences - September 13, 2019 Category: Drugs & Pharmacology Source Type: research

Overexpression of the gene product of ocular albinism 1 (GPR143/OA1) but not its mutant forms inhibit neurite outgrowth in PC12 cells
Publication date: Available online 11 September 2019Source: Journal of Pharmacological SciencesAuthor(s): Daiki Masukawa, Kaisei Yamada, Yoshio GoshimaAbstractNeurite outgrowth is a complex differentiation process regulated by external and/or internal mechanisms. Among external mechanisms, G-protein coupled receptors (GPCRs) have been implicated in this process, but the pathways involved are not fully understood. L-3,4-dihydroxyphenylalanine (L-DOPA) is considered to be inert by itself, and to relieve Parkinson’s disease through its conversion to dopamine. We have proposed that L-DOPA acts as a neurotransmitter. GPR1...
Source: Journal of Pharmacological Sciences - September 11, 2019 Category: Drugs & Pharmacology Source Type: research

Nitric oxide plays a critical role in methotrexate-induced hyperplasia of enterochromaffin cells containing 5-hydroxytryptamine in rat small intestine
Publication date: Available online 10 September 2019Source: Journal of Pharmacological SciencesAuthor(s): Yuho Takano, Megumi Hirano, Takuji Machida, Yusuke Obara, Naoya Hamaue, Kana Fujita, Masafumi Taniguchi, Tomoko Endo, Saki Shiga, Maiko Machida, Kenji Iizuka, Masahiko HirafujiAbstractThe role of nitric oxide (NO) in the changes in enterochromaffin cells and ileal 5-hydroxytryptamine (5-HT) content induced by a single i.p. administration of methotrexate was investigated in rats. Methotrexate significantly increased inducible NO synthase (iNOS) mRNA and protein expressions in the intestinal tissue at 96 h. Methotrexate ...
Source: Journal of Pharmacological Sciences - September 11, 2019 Category: Drugs & Pharmacology Source Type: research

Effects of 2′-3′-dihydroxy-4′,6′-dimethoxychalcone derived from green perilla on auricle thickness in chronic contact dermatitis model mice
Publication date: Available online 28 August 2019Source: Journal of Pharmacological SciencesAuthor(s): Yuki Takada-Takatori, Yuka Takeda, Risa Imai, Yasuhiko Izumi, Akinori Akaike, Katsuharu Tsuchida, Toshiaki KumeAbstractOxidative stress has been implicated in the pathogenesis of allergic contact dermatitis. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, an in vivo antioxidant system, induces antioxidant enzymes. In our previous studies, we isolated 2ʹ,3ʹ-dihydroxy-4ʹ,6ʹ-dimethoxychalcone (DDC) from green perilla and identified it as a novel activator of the Nrf...
Source: Journal of Pharmacological Sciences - September 5, 2019 Category: Drugs & Pharmacology Source Type: research

Participation of PKG and PKA-related pathways in the IFN-γ induced modulation of the BKCa channel activity in human cardiac fibroblasts
This study was devoted to elucidating the interferon (IFN)-γ-induced signaling pathway and the interaction between protein kinase G (PKG) and protein kinase A (PKA) through large-conductance Ca(2+)-activated K(+) channels in human cardiac fibroblasts. The IK currents were recorded using a whole-cell patch clamp method. A large depolarization (+50 mV) and a high Ca2+ concentration (pCa 6.0) were used in the internal pipette solution to activate only the KCa channels. Iberiotoxin (Ibtx), which selectively inhibits BKCa channels at a concentration of 100 nmol/l, caused a significant reduction of basal IK. Adding IFN-&ga...
Source: Journal of Pharmacological Sciences - August 31, 2019 Category: Drugs & Pharmacology Source Type: research

Effects of 2'-3'-dihydroxy-4',6'-dimethoxychalcone derived from green perilla on auricle thickness in chronic contact dermatitis model mice
Publication date: Available online 28 August 2019Source: Journal of Pharmacological SciencesAuthor(s): Yuki Takada-Takatori, Yuka Takeda, Risa Imai, Yasuhiko Izumi, Akinori Akaike, Katsuharu Tsuchida, Toshiaki KumeAbstractOxidative stress has been implicated in the pathogenesis of allergic contact dermatitis. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, an in vivo antioxidant system, induces antioxidant enzymes. In our previous studies, we isolated 2ʹ,3ʹ-dihydroxy-4ʹ,6ʹ-dimethoxychalcone (DDC) from green perilla and identified it as a novel activator of the Nrf2-ARE...
Source: Journal of Pharmacological Sciences - August 29, 2019 Category: Drugs & Pharmacology Source Type: research

Continued exposure of anti-cancer drugs to human iPS cell-derived cardiomyocytes can unmask their cardiotoxic effects
Publication date: Available online 27 August 2019Source: Journal of Pharmacological SciencesAuthor(s): Kazuho Sakamoto, Kohei Sakatoku, Shintaro Sugimoto, Nanami Iwasaki, Yusuke Sano, Masahiko Yamaguchi, Junko KurokawaAbstractAlthough the cardiotoxicity of anti-cancer drugs is an important issue, the underlying mechanisms remain unknown. To develop a sensitive assay system for cardiotoxicity, we examined effects of anti-cancer drugs on contractile functions of human iPS cell-derived cardiomyocytes by using non-invasive motion field imaging analysis with extended drug exposure time. We succeeded in continuously measuring st...
Source: Journal of Pharmacological Sciences - August 28, 2019 Category: Drugs & Pharmacology Source Type: research

Involvement of the persistent Na+ current in the diastolic depolarization and automaticity of the guinea pig pulmonary vein myocardium
In conclusion, late INa is involved in the diastolic depolarization and automaticity of the pulmonary vein myocardium. Late INa inhibitors appear to be effective therapeutic agents for atrial fibrillation with minimum adverse effects on the working myocardium. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - August 27, 2019 Category: Drugs & Pharmacology Source Type: research

Evaluation of the susceptibility of neurons and neural stem/progenitor cells derived from human induced pluripotent stem cells to anticancer drugs
In this study, we differentiated hiPSC-NSPCs into neurons and evaluated the susceptibility of hiPSC-neurons and parental hiPSC-NSPCs to anticancer drugs in vitro by ATP assay and immunocytostaining. The hiPSC-neurons were more resistant to anticancer drugs than the parental hiPSC-NSPCs. In the toxicity tests, high-dose cisplatin reduced the levels of ELAVL3/4, a neuronal marker, in the hiPSC-neurons. These results suggest that our methodology is potentially applicable for efficient determination of the toxicity of any drug to hiPSC-neurons. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - August 21, 2019 Category: Drugs & Pharmacology Source Type: research

Electrophysiological Characterization of a Small Molecule Activator on Human Ether-a-go-go-Related Gene (hERG) Potassium Channel
In conclusion, we identified a novel hERG channel activator HW-0168 that can be used for studying the physiological role of hERG in cardiac myocytes and may be beneficial for treating long QT syndrome. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - August 15, 2019 Category: Drugs & Pharmacology Source Type: research

Novel mouse model for evaluating in vivo efficacy of xCT inhibitor
Publication date: Available online 3 August 2019Source: Journal of Pharmacological SciencesAuthor(s): Ryosuke Yoshioka, Yusuke Fujieda, Yamato Suzuki, Osamu Kanno, Asako Nagahira, Tomohiro Honda, Masao Murakawa, Hiroshi YukiuraAbstractxCT, a well-known cystine transporter, is reported to be involved in the proliferation of various cells, such as cancer cells, immune cells, and fibroblasts. xCT inhibitor is expected to be a promising drug for cancer or immune diseases. However, there are little studies reporting that xCT inhibitors improve disease progression in vivo. To invent potent xCT inhibitors in vivo, we es...
Source: Journal of Pharmacological Sciences - August 10, 2019 Category: Drugs & Pharmacology Source Type: research

Targeted juglone blocks the invasion and metastasis of HPV-positive cervical cancer cells
This study was designed to acquire an understanding of the mechanism of invasion and metastasis in HPV-positive cells suppressed by juglone.It provides evidence of the advantageous use of juglone in the future.Graphical abstract (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - August 10, 2019 Category: Drugs & Pharmacology Source Type: research

Cognitive enhancer ST101 improves schizophrenia-like behaviors in neonatal ventral hippocampus-lesioned rats in association with improved CaMKII/PKC pathway
Publication date: Available online 8 August 2019Source: Journal of Pharmacological SciencesAuthor(s): Yasushi Yabuki, Lei Wu, Kohji FukunagaAbstractAtypical antipsychotics improve positive and negative symptoms but are not effective for treating cognitive impairments in patients with schizophrenia. We previously reported that cognitive impairments in neonatal ventral hippocampus (NVH)-lesioned rats show resistance to atypical antipsychotics risperidone and are associated with reduced calcium/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) signaling in memory-related regions. The cognitive enhance...
Source: Journal of Pharmacological Sciences - August 9, 2019 Category: Drugs & Pharmacology Source Type: research

LncRNA RMRP accelerates hypoxia-induced injury by targeting miR-214-5p in H9c2 cells
Conclusion: our findings demonstrated the novel molecular mechanism of RMRP/miR-214-5p/p53 axis on the regulation of hypoxia-induced myocardial injury in H9c2 cells, which might provide potential therapeutic targets for AMI treatment. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - August 8, 2019 Category: Drugs & Pharmacology Source Type: research

GdCl3 attenuates the glomerular sclerosis of streptozotocin (STZ) induced diabetic rats via inhibiting TGF-β/Smads signal pathway
In this study, we found that GdCl3 which was an agonist of Calcium-sensing receptor (CaSR) could repress the activation of TGF-β/Smads signal pathway induced by TGF-β1 or high glucose and then alleviated the accumulation of extracellular matrix (ECM) in mesangial cells and the kidney of type1 diabetic rats. Further study indicated that GdCl3 could induce the binding of CaSR and TβR II and then both of these two receptors translocated from cell membrane to cytoplasm, in this case, TβR II on the cell membrane was decreased and then desensitized to the stimulation of its ligand TGF-β1, so that the act...
Source: Journal of Pharmacological Sciences - August 7, 2019 Category: Drugs & Pharmacology Source Type: research

Genetic deletion of Cav3.2 T-type calcium channels abolishes H2S-dependent somatic and visceral pain signaling in C57BL/6 mice
Publication date: Available online 30 July 2019Source: Journal of Pharmacological SciencesAuthor(s): Kazuki Matsui, Maho Tsubota, Saaya Fukushi, Nene Koike, Hiroshi Masuda, Yoshihito Kasanami, Takaya Miyazaki, Fumiko Sekiguchi, Tsuyako Ohkubo, Shigeru Yoshida, Yutaro Mukai, Akira Oita, Mitsutaka Takada, Atsufumi KawabataAbstractWe tested whether genetic deletion of Cav3.2 T-type Ca2+ channels abolishes hydrogen sulfide (H2S)-mediated pain signals in mice. In Cav3.2-expressing HEK293 cells, Na2S, an H2S donor, at 100 μM clearly increased Ba2+ currents, as assessed by whole-cell patch-clamp recordings. In w...
Source: Journal of Pharmacological Sciences - August 5, 2019 Category: Drugs & Pharmacology Source Type: research

Effects of progesterone on hypoxia-induced inhibition of excitatory synaptic transmission in the rat nucleus tractus solitarius
Publication date: Available online 3 August 2019Source: Journal of Pharmacological SciencesAuthor(s): Yoshiaki Ohi, Daisuke Kodama, Akira HajiAbstrsctThe present study evaluated the ability of progesterone to alleviate the synaptic transmission disturbed by hypoxia in the nucleus tractus solitarius (NTS). Hypoxia with N2 inhibited spontaneous and tractus solitarius-evoked excitatory postsynaptic currents (sEPSCs and eEPSCs) in NTS neurons of the rat brainstem slice. An additional application of progesterone counteracted the hypoxia-induced inhibition of sEPSCs and eEPSCs without affecting the baseline currents. This effect...
Source: Journal of Pharmacological Sciences - August 4, 2019 Category: Drugs & Pharmacology Source Type: research

Novel mouse model for evaluating in vivo efficacy of xCT inhibitor
Publication date: Available online 3 August 2019Source: Journal of Pharmacological SciencesAuthor(s): Ryosuke Yoshioka, Yusuke Fujieda, Yamato Suzuki, Osamu Kanno, Asako Nagahira, Tomohiro Honda, Masao Murakawa, Hiroshi YukiuraAbstractxCT, a well-known cystine transporter, is reported to be involved in the proliferation of various cells, such as cancer cells, immune cells, and fibroblasts. xCT inhibitor is expected to be a promising drug for cancer or immune diseases. However, there are little studies reporting that xCT inhibitors improve disease progression in vivo. To invent potent xCT inhibitors in vivo, we established ...
Source: Journal of Pharmacological Sciences - August 4, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: June 2019Source: Journal of Pharmacological Sciences, Volume 140, Issue 2Author(s): (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - August 2, 2019 Category: Drugs & Pharmacology Source Type: research

Discovery of a novel chalcone derivative inhibiting CFTR chloride channel via AMPK activation and its anti-diarrheal application
This study aimed to identify novel chalcone derivatives with improved potency and explore their mechanism of action. Screening of 27 chalcone derivatives identified CHAL-025 as the most potent chalcone analog that reversibly inhibited CFTR-mediated Cl- secretion in T84 cells with an IC50 of ∼1.5 μM. As analyzed by electrophysiological and biochemical analyses, the mechanism of CFTR inhibition by CHAL-025 is through AMP-activated protein kinase (AMPK), a negative regulator of CFTR activity. Furthermore, western blot analyses and molecular dynamics (MD) results suggest that CHAL-025 activates AMPK by binding at the al...
Source: Journal of Pharmacological Sciences - August 2, 2019 Category: Drugs & Pharmacology Source Type: research

Effects of geldanamycin on neurite outgrowth-related proteins and kinases in nerve growth factor-differentiated pheochromocytoma 12 cells
Publication date: Available online 30 July 2019Source: Journal of Pharmacological SciencesAuthor(s): Keisuke Migita, Taichi Matsumoto, Kazuki Terada, Kazuhiko Ono, Shuji HaraAbstractHeat shock protein 90 (HSP90) antagonists are currently being evaluated as potential anticancer drugs. However, adverse effects related to these drugs, such as fatigue and pain, suggest that they affect neurons. Therefore, to understand the influence of HSP90 inhibitors on neurons, we investigated the effects of geldanamycin, an HSP90 antagonist, on nerve growth factor (NGF)-differentiated pheochromocytoma 12 (PC12) cells, particularly, on the ...
Source: Journal of Pharmacological Sciences - July 31, 2019 Category: Drugs & Pharmacology Source Type: research

Genetic deletion of Cav3.2 T-type calcium channels abolishes H2S-dependent somatic and visceral pain signaling in C57BL/6 mice
Publication date: Available online 30 July 2019Source: Journal of Pharmacological SciencesAuthor(s): Kazuki Matsui, Maho Tsubota, Saaya Fukushi, Nene Koike, Hiroshi Masuda, Yoshihito Kasanami, Takaya Miyazaki, Fumiko Sekiguchi, Tsuyako Ohkubo, Shigeru Yoshida, Yutaro Mukai, Akira Oita, Mitsutaka Takada, Atsufumi KawabataAbstractWe tested whether genetic deletion of Cav3.2 T-type Ca2+ channels abolishes hydrogen sulfide (H2S)-mediated pain signals in mice. In Cav3.2-expressing HEK293 cells, Na2S, an H2S donor, at 100 μM clearly increased Ba2+ currents, as assessed by whole-cell patch-clamp recordings. In wild-type C57BL/...
Source: Journal of Pharmacological Sciences - July 30, 2019 Category: Drugs & Pharmacology Source Type: research

Retinoic acid promotes barrier functions in human iPSC-derived intestinal epithelial monolayers
Publication date: Available online 26 July 2019Source: Journal of Pharmacological SciencesAuthor(s): Shigeru Yamada, Yasunari KandaAbstractVitamin A (VA) is a fat-soluble micronutrient that plays essential roles in various biological processes, including cell growth, differentiation, and apoptosis. In the intestine, VA are known to promote mucosal homeostasis and immunity. However, the effect of VA in intestinal development has not been well elucidated. In the present study, we generated human intestine organoids from human induced pluripotent stem cells (iPSCs), and investigated the effect of the VA active metabolite all-...
Source: Journal of Pharmacological Sciences - July 27, 2019 Category: Drugs & Pharmacology Source Type: research

Paracetamol inhibits Ca2+ permeant ion channels and Ca2+ sensitization resulting in relaxation of precontracted airway smooth muscle
Publication date: Available online 24 July 2019Source: Journal of Pharmacological SciencesAuthor(s): Yuan-Yuan Chen, Meng-Fei Yu, Xiao-Xue Zhao, Jinhua Shen, Yong-Bo Peng, Ping Zhao, Lu Xue, Weiwei Chen, Li-Qun Ma, Gangjian Qin, Jiapei Dai, Qing-Hua LiuAbstrctThe purpose of this study was to screen a bronchodilator from old drugs and elucidate the underlying mechanism. Paracetamol (acetaminophen) is a widely used analgesic and antipyretic drug. It has been reported that it inhibits the generation of prostaglandin and histamine, which play roles in asthma. These findings led us to explore whether paracetamol could be a pote...
Source: Journal of Pharmacological Sciences - July 25, 2019 Category: Drugs & Pharmacology Source Type: research

Schisandra Chinensis Acidic Polysaccharide Partialy Reverses Acetaminophen-Induced Liver Injury in mice
In conclusion, we speculated that the protective activities of SCAP on the APAP-induced mouse model of acute liver injury might be related to its antioxidation, anti-inflammation and anti-apoptosis properties. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - July 25, 2019 Category: Drugs & Pharmacology Source Type: research

Donepezil ameliorates oxaliplatin-induced peripheral neuropathy via a neuroprotective effect
Publication date: Available online 19 July 2019Source: Journal of Pharmacological SciencesAuthor(s): Takehiro Kawashiri, Shiori Shimizu, Nao Shigematsu, Daisuke Kobayashi, Takao ShimazoeAbstractOxaliplatin induces severe peripheral neuropathy. The effect of donepezil, a drug used for treatment of Alzheimer’s disease, on oxaliplatin-induced peripheral neuropathy was investigated using both in vivo and in vitro models. Donepezil effectively attenuated oxaliplatin- and cisplatin-induced inhibition of neurite outgrowth in cultured PC12 cells. In a rat model, repeated oral administration of donepezil (5 times/week for 4 w...
Source: Journal of Pharmacological Sciences - July 20, 2019 Category: Drugs & Pharmacology Source Type: research

Engeletin inhibits Lipopolysaccharide/D-galactosamine-induced liver injury in mice through activating PPAR-γ
Publication date: Available online 19 July 2019Source: Journal of Pharmacological SciencesAuthor(s): Qing Tian, Guijie Wang, Yamin Zhang, Fubo Zhang, Long Yang, Zirong Liu, Zhongyang ShenAbstractLiver injury is a serious clinical syndrome that characterized by inflammatory response. Engeletin is known to have anti-inflammatory activity. However, the effects of engeletin on liver injury remain unclear. We aimed to assess the protective effect of engeletin on Lipopolysaccharide (LPS)/D-galactosamine (D-gal)-induced liver injury in mice. Engeletin was administered intraperitoneally 1 h before and 12 h after LPS/D-gal treatmen...
Source: Journal of Pharmacological Sciences - July 20, 2019 Category: Drugs & Pharmacology Source Type: research

Analysis of electro-mechanical relationship in human iPS cell-derived cardiomyocytes sheets under proarrhythmic condition assessed by simultaneous field potential and motion vector recordings
Publication date: Available online 19 July 2019Source: Journal of Pharmacological SciencesAuthor(s): Atsushi Sugiyama, Mihoko Hagiwara-Nagasawa, Ryuichi Kambayashi, Ai Goto, Koki Chiba, Atsuhiko T. Naito, Yasunari Kanda, Akio Matsumoto, Hiroko Izumi-NakasekoAbstractWe investigated the electro-mechanical relationship of human iPS cell-derived cardiomyocyte sheets under arrhythmic condition, which was induced by digitalis intoxication along with the electrical train stimulation (n=4). We adopted motion vector analysis by high-speed video microscopy and extracellular field potential recording by 64-microelectrode array system...
Source: Journal of Pharmacological Sciences - July 20, 2019 Category: Drugs & Pharmacology Source Type: research

Transplantation of cardiac Sca-1-positive cells rather than c-Kit-positive cells preserves mitochondrial oxygen consumption of the viable myocardium following myocardial infarction in rats
In this study, we compared the effect of transplantation of isolated Sca-1+ cells and c-Kit+ cells with that of the crude CDCs (CrCDCs). Focusing on the differences in the ability for secretion of paracrine factors among 3 types of cells, we determined the effects of transplantation of these cells on cardiac intracellular signaling and mitochondrial function in rats with permanently ligated coronary arteries. We showed that the transplantation of these cells resulted in a preservation of the cardiac pump function and mitochondrial respiration at the 8th week after myocardial infarction. However, mitochondrial function in t...
Source: Journal of Pharmacological Sciences - July 20, 2019 Category: Drugs & Pharmacology Source Type: research

The therapeutic effects of Jaceosidin on lipopolysaccharide-induced acute lung injury in mice
Publication date: Available online 18 July 2019Source: Journal of Pharmacological SciencesAuthor(s): Xiao-lei Huang, Xiao-chen Wei, Leng-qiu Guo, Lei Zhao, Xi-hua Chen, Ya-dong Cui, Jie Yuan, Dao-feng Chen, Jian ZhangAbstractAcute lung injury (ALI) results from various factors including uncontrolled pulmonary inflammation, oxidative damage and the over-activated complement with high mortality rates. Jaceosidin was a flavonoid compound with significant anti-complement activity. We aimed to investigate the therapeutic effects of Jaceosidin on ALI induced by lipopolysaccharide (LPS). Mice were orally administrated with Jaceos...
Source: Journal of Pharmacological Sciences - July 19, 2019 Category: Drugs & Pharmacology Source Type: research

DNA methylation was involved in Total glucosides of Paeony regulating ERα for the treatment of female Systemic lupus erythematosus mice
In this study, we found that TGP treatment significantly decreased the expression of ERα by up-regulating ERα promoter methylation levels. Further investigation revealed that treatment with TGP increased the expression of DNMT in lupus mice. We also used DNA methyltransferase inhibitors to verify whether DNA methylation was involved in these process. HE staining results showed that TGP can reduce renal injury in SLE mice. Moreover, cytokines including IFN-γ, IL6 and IL12 expression and dsDNA levels in serum were inhibited by TGP treatment. These findings indicate that TGP inhibits autoimmunity in SLE mice...
Source: Journal of Pharmacological Sciences - July 11, 2019 Category: Drugs & Pharmacology Source Type: research

IRR is involved in glucose-induced endocytosis after insulin secretion
Publication date: Available online 5 July 2019Source: Journal of Pharmacological SciencesAuthor(s): Mami Yamaokax, Takeshi Terabayashi, Tomoki Nishioka, Kozo Kaibuchi, Tomohisa Ishikawa, Toshimasa Ishizaki, Toshihide KimuraAbstractEndocytosis after insulin secretion plays a pivotal role in the regulation of insulin secretion in pancreatic β-cells. Our recent study suggested that EPI64, a GTPase activating protein for Rab27a, contributes to the regulation of glucose-induced endocytosis, which is mediated by the GDP-bound form of Rab27a. Here, we identified insulin receptor-related receptor (IRR) as an EPI64-interacting...
Source: Journal of Pharmacological Sciences - July 7, 2019 Category: Drugs & Pharmacology Source Type: research

Establishment of Enzyme-linked Immunosorbent Facilitated Antigen Binding as a Biomarker Assay for Japanese Cedar Pollen Allergy Immunotherapy
Conclusion; The JC pollen ELIFAB assay represents a simple, cell-free biomarker assay for monitoring the development of IgE-blocking antibody activity during JC pollen AIT. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - July 5, 2019 Category: Drugs & Pharmacology Source Type: research

Possible biased analgesic of hydromorphone through the G protein-over β-arrestin-mediated pathway: cAMP, CellKeyTM, and receptor internalization analyses
Publication date: Available online 2 July 2019Source: Journal of Pharmacological SciencesAuthor(s): Sei Manabe, Kanako Miyano, Yuriko Fujii, Kaori Ohshima, Yuki Yoshida, Miki Nonaka, Miaki Uzu, Yoshikazu Matsuoka, Tetsufumi Sato, Yasuhito Uezono, Hiroshi MorimatsuAbstractMorphine, fentanyl, and oxycodone are widely used as analgesics, and recently hydromorphone has been approved in Japan. Although all of these are selective for μ-opioid receptors (MORs) and have similar structures, their analgesic potencies and adverse effects (AEs) are diverse. Recent molecular analyses of MOR signaling revealed that the G protein-medi...
Source: Journal of Pharmacological Sciences - July 4, 2019 Category: Drugs & Pharmacology Source Type: research

Muscarinic M1 receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABAB receptors rather than GABAA receptors in mice
Publication date: Available online 28 June 2019Source: Journal of Pharmacological SciencesAuthor(s): Keisuke Migita, Akiko Nishimura, Fumihiro Eto, Kohei Koga, Taichi Matsumoto, Kazuki Terada, Shuji Hara, Kenji HondaAbstractCholinergic neurons play an important role in the higher functions of the brain, such as the memory, cognition, and nociception. However, the exact mechanism behind how the stimulation of all the muscarinic M1 receptors in the entire brain results in the alleviation of partial sciatic nerve ligation (PSNL)-induced mechanical hypersensitivity has not been investigated. Thus, we examined which subtype of ...
Source: Journal of Pharmacological Sciences - June 28, 2019 Category: Drugs & Pharmacology Source Type: research

Chronic memantine administration prevents ouabain-induced hyperactivity in mice via maintenance of Na+, K+-ATPase activity in the hippocampus
Publication date: Available online 21 June 2019Source: Journal of Pharmacological SciencesAuthor(s): Yuki Kurauchi, Taishi Yamada, Akinori Hisatsune, Takahiro Seki, Hiroshi KatsukiAbstractWe have previously reported that mice received intracerebroventricular injection of ouabain, an inhibitor of Na+, K+-ATPase, exhibited hyperactivity via overactivation of glutamatergic neurons. Here we investigated the effects of memantine, a blocker of N-methyl-d-aspartate receptors, on ouabain-induced hyperactivity. In mice that received ouabain injection, chronic memantine administration prevented the hyperactivity and the decrease in ...
Source: Journal of Pharmacological Sciences - June 22, 2019 Category: Drugs & Pharmacology Source Type: research

Systematic expression analysis of genes related to generation of action potentials in human iPS cell-derived cardiomyocytes
Publication date: Available online 21 June 2019Source: Journal of Pharmacological SciencesAuthor(s): Masami Kodama, Kazuharu Furutani, Reiko Kimura, Tomoko Ando, Kazuho Sakamoto, Shushi Nagamori, Takashi Ashihara, Yoshihisa Kurachi, Yuko Sekino, Tetsushi Furukawa, Yasunari Kanda, Junko KurokawaAbstractHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a valuable tool to characterize the pharmacology and toxic effects of drugs on heart cells. In particular, hiPSC-CMs can be used to identify drugs that generate arrhythmias. However, it is unclear whether the expression of genes related to generation o...
Source: Journal of Pharmacological Sciences - June 22, 2019 Category: Drugs & Pharmacology Source Type: research

Extracellular Ca2+ promotes nitric oxide production via Ca2+-sensing receptor-Gq/11 protein-endothelial nitric oxide synthase signaling in human vascular endothelial cells
This study examined the possible involvement of Ca2+-sensing receptor (CaSR) in nitric oxide (NO) production in human vascular endothelial cells. Extracellular Ca2+ elevated the intracellular Ca2+ concentration, the endothelial NO synthase (eNOS) phosphorylation level, and NO release from the cells. These responses were inhibited by a CaSR antagonist and a Gq/11 protein inhibitor. Application of an endothelial cell suspension induced vasorelaxation in isolated rat thoracic aorta precontracted by phenylephrine. Adding an NO scavenger to the organ bath abolished this vasorelaxation response. These results suggest that extrac...
Source: Journal of Pharmacological Sciences - June 22, 2019 Category: Drugs & Pharmacology Source Type: research