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Journal of Pharmacological Sciences

Sedona Lockhart, Akira Sawa, Minae Niwa
Adverse events in childhood and adolescence, such as social neglect or drug abuse, are known to lead to behavioral changes in young adulthood. This is particularly true for the subset of people who are intrinsically more vulnerable to stressful conditions. Yet the underlying mechanisms for such developmental trajectory from early life insult to aberrant adult behavior remains elusive. Adolescence is a period of dynamic physiological, psychological, and behavioral changes, encompassing a distinct neurodevelopmental stage called the 'critical period'...
May 3, 2018: Journal of Pharmacological Sciences
Kohei Yoshihara, Tsuyoshi Matsuda, Yuta Kohro, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Makoto Tsuda
The role of astrocytes in the spinal dorsal horn (SDH) for sensory information processing under normal conditions is poorly understood. In this study, we investigated whether SDH astrocytes respond to noxious and innocuous stimuli to the skin of normal mice using in vivo two-photon Ca2+ imaging under anesthesia. We found that noxious stimulation evoked by intraplantar formalin injection provoked an elevation in intracellular Ca2+ levels in SDH astrocytes. By contrast, neither instantaneous noxious pinching nor innocuous stimuli (cooling or brushing) to the hindpaw elicited astrocytic Ca2+ responses...
May 3, 2018: Journal of Pharmacological Sciences
Hongliang Li, Sung Eun Shin, Jin Ryeol An, Mi Seon Seo, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Amy L Firth, Dae-Sung Lee, Mi-Jin Yim, Jeong Min Lee, Grace Choi, Il-Whan Choi, Won Sun Park
We investigated the effect of the tricyclic antidepressant clomipramine on voltage-dependent K+ (Kv) channels in native rabbit coronary arterial smooth muscle cells. Our results showed that clomipramine inhibited vascular Kv channels in a concentration-dependent manner, with an IC50 value of 8.61 ± 4.86 μM and a Hill coefficient (n) of 0.58 ± 0.07. The application of 10 μM clomipramine did not affect the activation curves of the Kv channels; however, the inactivation curves of the Kv channels were shifted toward a more negative potential...
April 27, 2018: Journal of Pharmacological Sciences
Shuhei Takahashi, Akinori Hisatsune, Yuki Kurauchi, Takahiro Seki, Hiroshi Katsuki
Polysulfides are endogenous sulfur-containing molecular species that may regulate various cellular functions. Here we examined the effect of polysulfides exogenously applied to rat midbrain slice cultures, to address their potential neuroprotective actions. Na2 S3 at concentrations of 10 μM or higher prevented 1-methyl-4-phenylpyridinium (MPP+ )-induced loss of dopaminergic neurons. Na2 S4 at 10 μM also protected dopaminergic neurons from MPP+ cytotoxicity, whereas Na2 S and Na2 S2 at the same concentration had no significant effect...
April 20, 2018: Journal of Pharmacological Sciences
Hui Li, Xin Chen, Shu-Jun Zhou
Dauricine, isolated from Menispermum dauricum, has been widely used for treatment of various diseases, including cardiac ischemia and inflammation-related diseases. However, little is known regarding to the effect of dauricine on severe pneumonia. Therefore, the aim was to investigate the effect of dauricine on severe pneumonia and its mechanism during progress. Herein, H5N1 and Streptococcus pneumoniae (D39) were conducted to induce severe pneumonia in both BEAS-2B cells and mice. In vitro, dauricine reversed the protein and mRNA expressions of TNF-α, IL-6 and IL-1β, examined by ELISA and qRT-PCR assay, respectively...
April 19, 2018: Journal of Pharmacological Sciences
Akira Takahara, Shuhei Nozaki, Akane Ishiguro, Kaori Okamura, Xin Cao, Megumi Aimoto, Yoshinobu Nagasawa
We compared dilator actions of representative four Ca2+ channel blockers on the isolated lower esophagus sphincter (LES) and thoracic aorta from rats. Verapamil, diltiazem, nifedipine and cilnidipine suppressed KCl-induced contractions of LES and thoracic aorta in a concentration-dependent manner. The order of selectivity for LES, which was calculated as ratio of IC50 value for thoracic aorta divided by that for LES, was diltiazem > verapamil > nifedipine > cilnidipine. These results suggest that diltiazem more preferentially dilates the LES whereas cilnidipine is expected to have lower potential risk of gastroesophageal dysfunction during the antihypertensive therapy...
April 19, 2018: Journal of Pharmacological Sciences
Manabu Yonekura, Nami Kondoh, Chong Han, Yuichi Toyama, Takayoshi Ohba, Kyoichi Ono, Shirou Itagaki, Hirofumi Tomita, Manabu Murakami
The heart of the medaka, a small fish native to East Asia, has electrophysiological aspects similar to mammalian hearts. We found that the heart rates of medaka were more similar to humans than mice or rats. Medaka exhibited similar electrocardiogram patterns to those of humans, suggesting a similarity in cardiac impulse formation and propagation. Their hearts also exhibited similar responsiveness to verapamil, a calcium channel antagonist; atropine, a parasympathetic nerve blocker; propranolol, a sympathetic β-adrenergic blocker; and isoproterenol, a sympathetic β-adrenergic agonist...
April 12, 2018: Journal of Pharmacological Sciences
Yoshiyuki Meguro, Kanako Miyano, Shigeto Hirayama, Yuki Yoshida, Naoto Ishibashi, Takumi Ogino, Yuriko Fujii, Sei Manabe, Moeko Eto, Miki Nonaka, Hideaki Fujii, Yoichi Ueta, Minoru Narita, Naohiro Sata, Toshihiko Yada, Yasuhito Uezono
Oxytocin (OT) is a 9-amine neuropeptide that plays an essential role in mammalian labor, lactation, maternal bonding, and social affiliation. OT has been reported to exert an analgesic effect in both humans and animals, and the results of certain animal experiments have shown that the analgesic effect of OT is partially blocked by opioid receptor antagonists. To investigate the relationship between OT and μ opioid receptor (MOR), we evaluated how OT affects MOR in vitro by performing an electrical impedance-based receptor biosensor assay (CellKey™ assay), an intracellular cAMP assay, and a competitive receptor-binding analysis by using cells stably expressing human MOR and OT receptor...
April 11, 2018: Journal of Pharmacological Sciences
Shan Jiang, Yong Wu, De-Fang Fang, Ying Chen
Hypothermic preconditioning is an effective treatment for limiting ischemic injury, but the mechanism is poorly understood. This study was aimed to explore the effect of hypothermic and ketamine preconditioning on oxygen and glucose deprivation (OGD) induced neuronal injury in mouse hippocampal slices, and to investigate its possible mechanism. The population spike (PS) was recorded in the CA1 region of mouse hippocampal slices using extracellular recordings, Na+ /K+ ATPase activity in slices was determined by spectrophotometer and the expression of Cyclooxygenase-2 (COX-2) was measured by Western blot...
April 7, 2018: Journal of Pharmacological Sciences
Dongfeng Zhao, Xiaofeng Li, Yongjian Zhao, Ping Qiao, Dezhi Tang, Yan Chen, Chunchun Xue, Chenguang Li, Shufen Liu, Jing Wang, Sheng Lu, Qi Shi, Yan Zhang, Yufeng Dong, Yongjun Wang, Bing Shu, Xu Feng
Postmenopausal osteoporosis (POP) is quite prevalent and many new drugs are under development to obtain better therapeutic outcomes. Oleanolic acid (OA) has been reported to prevent bone loss in ovariectomized (OVX) rats by stimulating osteoblastogenesis. One previous study has demonstrated that acetate of OA suppressed lipopolysaccharides (LPS)-induced bone loss in mice. However, the role of OA in the receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis is still not elucidated...
April 6, 2018: Journal of Pharmacological Sciences
Takeshi Miyahara, Naoko Adachi, Takahiro Seki, Izumi Hide, Shigeru Tanaka, Naoaki Saito, Masahiro Irifune, Norio Sakai
Propofol is the most commonly used anesthetic. Immunohistochemical studies have reported that propofol translocated protein kinase Cs (PKCs) in cardiomyocyte in a subtype-specific manner; however detailed features of the propofol-induced translocation of PKCs remain unknown. In this study, we performed real-time observation of propofol-induced PKC translocation in SH-SY5Y cells expressing PKCs fused with a fluorescent protein. Propofol unidirectionally translocated γPKC-GFP, a conventional PKC, and ζPKC-GFP, an atypical PKC, to the plasma membrane and nucleus, respectively, whereas the propofol-induced translocation of novel PKCs was diverse and subtype-specific among δPKC, εPKC and ηPKC...
April 6, 2018: Journal of Pharmacological Sciences
Rina Ando, Mohammed Emamussalehin Choudhury, Yuki Yamanishi, Win Thiri Kyaw, Madoka Kubo, Mariko Kannou, Noriko Nishikawa, Junya Tanaka, Masahiro Nomoto, Masahiro Nagai
Treatment with dopaminergic agents result excessive daytime sleepiness (EDS) and some studies have shown the benefit of using modafinil for treating excessive daytime sleepiness of Parkinson's disease (PD) patient. We investigated whether modafinil have ameliorative properties against levodopa induced excessive nighttime sleepiness (ENS) in MPTP-treated murine nocturnal PD model. Our EEG analyses of whole day recordings revealed that modafinil reduce ENS of this nocturnal PD models with levodopa medications...
March 31, 2018: Journal of Pharmacological Sciences
Takafumi Horishita, Nobuyuki Yanagihara, Susumu Ueno, Dan Okura, Reiko Horishita, Tomoko Minami, Yuichi Ogata, Yuka Sudo, Yasuhito Uezono, Takashi Kawasaki
The neurosteroid allopregnanolone has potent analgesic effects, and its potential use for neuropathic pain is supported by recent reports. However, the analgesic mechanisms are obscure. The voltage-gated sodium channels (Nav ) α subunit Nav 1.3 is thought to play an essential role in neuropathic pain. Here, we report the effects of allopregnanolone sulfate (APAS) on sodium currents (INa ) in Xenopus oocytes expressing Nav 1.3 with β1 or β3 subunits. APAS suppressed INa of Nav 1.3 with β1 and β3 in a concentration-dependent manner (IC50 values; 75 and 26 μmol/L)...
March 30, 2018: Journal of Pharmacological Sciences
Mari Chiyoya, Kazuhiko Seya, Zaiqiang Yu, Kazuyuki Daitoku, Shigeru Motomura, Tadaatsu Imaizumi, Ikuo Fukuda, Ken-Ichi Furukawa
Calcified aortic valve stenosis (CAS) is a common heart valve disease in elderly people, and is mostly accompanied by ectopic valve calcification. We recently demonstrated that tumor necrosis factor-α (TNF-α) induces calcification of human aortic valve interstitial cells (HAVICs) obtained from CAS patients. In this study, we investigated the role of matrix Gla protein (MGP), a known calcification inhibitor that antagonizes bone morphogenetic protein 2 (BMP2) in TNF-α-induced calcification of HAVICs. HAVICs isolated from aortic valves were cultured, and calcification was significantly induced with 30 ng/mL TNF-α...
March 29, 2018: Journal of Pharmacological Sciences
Suchitra Matsukura, Yuji Nakamura, Kiyotaka Hoshiai, Takashi Hayashi, Tadashi Koga, Ai Goto, Koki Chiba, Nur Jaharat Lubna, Mihoko Hagiwara-Nagasawa, Hiroko Izumi-Nakaseko, Kentaro Ando, Atsuhiko T Naito, Atsushi Sugiyama
Effects of moxifloxacin on QTc as well as proarrhythmic surrogate markers including J-Tpeak c, Tpeak -Tend and short-term variability (STV) of repolarization were examined by using both standard E14 time-based evaluation and exposure-response modeling. The study was conducted with a single-blind, randomized, single-dose, placebo-controlled and two-period cross-over design in healthy Filipino subjects. QT interval was corrected by Fridericia's formula (QTcF). In the E14 time-based evaluation of ECG data, the largest ΔΔQTcF with 90% confidence interval was 14...
March 27, 2018: Journal of Pharmacological Sciences
Akane Morita, Shohei Sawada, Asami Mori, Shiho Arima, Kenji Sakamoto, Tohru Nagamitsu, Tsutomu Nakahara
Abnormalities in retinal blood vessels and neuronal function persist in eyes undergoing retinopathy of prematurity. In this study, we examined morphological and functional changes in retinal blood vessels and neurons in mice that had undergone short-term interruption of retinal vascular development through inhibition of vascular endothelial growth factor (VEGF) signaling. In mice treated with the VEGF receptor tyrosine kinase inhibitor KRN633 on postnatal day (P) 0 and 1, the vascular density in the retinal surface increased by P12, but development of deep retinal vascular plexus and choroidal vasculature was delayed until P14...
March 14, 2018: Journal of Pharmacological Sciences
Yoichi Sunagawa, Masafumi Funamoto, Shogo Sono, Kana Shimizu, Satoshi Shimizu, Mai Genpei, Yusuke Miyazaki, Yasufumi Katanasaka, Eriko Morimoto, Morio Ueno, Maki Komiyama, Hideaki Kakeya, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
The natural compound, curcumin (CUR), possesses several pharmacological properties, including p300-specific histone acetyltransferase (HAT) inhibitory activity. In our previous study, we demonstrated that CUR could prevent the development of cardiac hypertrophy by inhibiting p300-HAT activity. Other major curcuminoids isolated from Curcuma longa including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are structural analogs of CUR. In present study, we first confirmed the effect of these three curcuminoid analogs on p300-HAT activity and cardiomyocyte hypertrophy...
March 13, 2018: Journal of Pharmacological Sciences
Shoya Shiromizu, Naoki Kusunose, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo
Proliferation of acute lymphoblastic leukemic cells is nutritionally dependent on the external supply of asparagine. l-asparaginase, an enzyme hydrolyzing l-asparagine in blood, is used for treatment of acute lymphoblastic leukemic and other related blood cancers. Although previous studies demonstrated that l-asparaginase suppresses the proliferation of cultured solid tumor cells, it remains unclear whether this enzyme prevents the growth of solid tumors in vivo. In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice...
March 12, 2018: Journal of Pharmacological Sciences
Takayuki Hori, Motoshi Ouchi, Naoyuki Otani, Masakatsu Nohara, Asuka Morita, Yusuke Otsuka, Promsuk Jutabha, Ikuko Shibasaki, Yasushi Matsushita, Tomoe Fujita, Hirotsugu Fukuda, Naohiko Anzai
The purpose of this study was to create novel urate under-excretion animal models using pyrazinamide and to evaluate whether dihydropyridine calcium channel blockers (CCBs) have uricosuric effects in vivo. Adult male ICR mice were treated with pyrazinamide, vehicle (dimethyl sulfoxide: DMSO), or tap water. Thirty minutes later, pyrazinamide-treated mice were given benzbromarone, losartan, nilvadipine, nitrendipine, nifedipine or azelnidipine. Six hours after the second administration, urine (by urinary bladder puncture) and plasma were collected to measure uric acid and creatinine levels, and fractional excretion of uric acid (FEUA) and creatinine clearance (Ccr) were calculated and evaluated...
March 8, 2018: Journal of Pharmacological Sciences
Yuma Ito, Masaki Fukui, Mamoru Kanda, Ko Morishita, Yoshimichi Shoji, Tatsuya Kitao, Eiichi Hinoi, Hiroaki Shirahase
The anti-diabetic and anti-obesity effects of the allosteric protein tyrosine phosphatase 1B (PTP1B) inhibitor 4-(biphenyl-4-ylmethylsulfanylmethyl)-N-(hexane-1-sulfonyl)benzoylamide (KY-226) were pharmacologically evaluated. KY-226 inhibited human PTP1B activity (IC50  = 0.28 μM), but did not exhibit peroxisome proliferator-activated receptor γ (PPARγ) agonist activity. In rodent preadipocytes (3T3-L1), KY-226 up to 10 μM had no effects on adipocyte differentiation, whereas pioglitazone, a PPARγ agonist, markedly promoted it...
March 6, 2018: Journal of Pharmacological Sciences
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