Journal of pharmacological sciences最新文献_第7页

Characterization of cardiovascular profile of anti-influenza drug peramivir: A reverse-translational study using the isoflurane-anesthetized dog 抗流感药物帕拉米韦的心血管特征：利用异氟醚麻醉狗进行的逆转录研究

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-02 DOI: 10.1016/j.jphs.2024.02.002

Ryuichi Kambayashi, Ai Goto, Hiroko Izumi-Nakaseko, Yoshinori Takei, Atsushi Sugiyama

{"title":"Characterization of cardiovascular profile of anti-influenza drug peramivir: A reverse-translational study using the isoflurane-anesthetized dog","authors":"Ryuichi Kambayashi, Ai Goto, Hiroko Izumi-Nakaseko, Yoshinori Takei, Atsushi Sugiyama","doi":"10.1016/j.jphs.2024.02.002","DOIUrl":"10.1016/j.jphs.2024.02.002","url":null,"abstract":"<div><p>An injectable anti-influenza drug peramivir has been reported to induce QT-interval prolongation in some phase III studies, although its thorough QT/QTc study was negative. We investigated the discrepancy among those clinical studies using isoflurane-anesthetized beagle dogs (n = 4). Peramivir in doses of 1 mg/kg/10 min (sub-therapeutic dose) followed by 10 mg/kg/10 min (clinically-relevant dose) was intravenously administered. Peramivir prolonged QT interval/QTcV and T<sub>peak</sub>-T<sub>end</sub>, and tended to delay ventricular repolarization in a reverse-frequency dependent manner, indicating I<sub>Kr</sub> inhibition in vivo. Meanwhile, peramivir did not alter P-wave duration, PR interval or QRS width, indicating a lack of impact on cardiac conduction via Na<sup>+</sup> or Ca<sup>2+</sup> channel inhibition in vivo. Peramivir prolonged T<sub>peak</sub>-T<sub>end</sub> and tended to prolong terminal repolarization period, which would develop substrates for initiating and maintaining spiral reentry, respectively. Meanwhile, peramivir did not prolong J-T<sub>peak</sub>c, which could not induce early afterdepolarization, a trigger inducing torsade de pointes. Thus, our results support that clinical dose exposure of peramivir can delay the ventricular repolarization in influenza patients. Peramivir has only a small potential to induce torsade de pointes in patients with the intact hearts, but caution should be paid on its use for patients formerly having the trigger for torsade de pointes.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 3","pages":"Pages 218-224"},"PeriodicalIF":3.5,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000112/pdfft?md5=81b7b603299d32dfc39fa0d2a6caf2e6&pid=1-s2.0-S1347861324000112-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139679479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

JTT-654, an 11-beta hydroxysteroid dehydrogenase type 1 inhibitor, improves hypertension and diabetic kidney injury by suppressing angiotensinogen production JTT-654 是一种 11-beta 类羟基类固醇脱氢酶 1 型抑制剂，可通过抑制血管紧张素原的生成来改善高血压和糖尿病肾损伤

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-02 DOI: 10.1016/j.jphs.2024.02.001

Shiro Heitaku, Tomohiko Sasase, Tomohiro Sotani, Mimi Maki, Takashi Kawai, Hisayo Morinaga, Jun Nishiu

{"title":"JTT-654, an 11-beta hydroxysteroid dehydrogenase type 1 inhibitor, improves hypertension and diabetic kidney injury by suppressing angiotensinogen production","authors":"Shiro Heitaku, Tomohiko Sasase, Tomohiro Sotani, Mimi Maki, Takashi Kawai, Hisayo Morinaga, Jun Nishiu","doi":"10.1016/j.jphs.2024.02.001","DOIUrl":"10.1016/j.jphs.2024.02.001","url":null,"abstract":"<div><p>11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays an important role in regulating the expression of glucocorticoid actions in target tissues. Overexpression of 11β-HSD1 in mouse adipose tissue causes a metabolic syndrome-like phenotype, leading to hypertension. Although, many 11β-HSD1 inhibitors have been studied, few have shown a clear ameliorative effect against hypertension. We investigated whether JTT-654, a novel 11β-HSD1 inhibitor, ameliorated hypertension and elucidated the underlying mechanisms. JTT-654 showed inhibitory effects on angiotensinogen production in cortisone-treated 3T3-L1 adipocytes and in a rat model. JTT-654 improved hypertension not only in cortisone-treated rats and spontaneously hypertensive rats (SHR), but also in SHR/NDmcr-cp rats. In the SHR study, JTT-654 and losartan showed the same degree of antihypertensive efficacy. In addition, JTT-654 ameliorated diabetic nephropathy by suppressing renal angiotensinogen production in SHR/NDmcr-cp rats. These effects of JTT-654 were independent of its insulin-sensitizing effects, and similar effects were not observed for pioglitazone, an insulin sensitizer. Moreover, JTT-654 did not affect normotension or hypothalamus-pituitary-adrenal (HPA) axis function in normal Sprague-Dawley rats. Our results indicate that JTT-654 ameliorates hypertension and diabetic nephropathy by inhibiting 11β-HSD1 in the adipose tissue, liver, and kidney.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 246-255"},"PeriodicalIF":3.5,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000100/pdfft?md5=4e3cefc35b67be376843d00f844aa38b&pid=1-s2.0-S1347861324000100-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139665067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of amino acid transporter LAT1 in cancer cells suppresses G0/G1-S transition by downregulating cyclin D1 via p38 MAPK activation 抑制癌细胞中的氨基酸转运体 LAT1，通过 p38 MAPK 激活下调细胞周期蛋白 D1，从而抑制 G0/G1-S 转变

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-01-30 DOI: 10.1016/j.jphs.2024.01.007

Xinyu Zhou , Ryuichi Ohgaki , Chunhuan Jin , Minhui Xu , Hiroki Okanishi , Hitoshi Endou , Yoshikatsu Kanai

{"title":"Inhibition of amino acid transporter LAT1 in cancer cells suppresses G0/G1-S transition by downregulating cyclin D1 via p38 MAPK activation","authors":"Xinyu Zhou , Ryuichi Ohgaki , Chunhuan Jin , Minhui Xu , Hiroki Okanishi , Hitoshi Endou , Yoshikatsu Kanai","doi":"10.1016/j.jphs.2024.01.007","DOIUrl":"10.1016/j.jphs.2024.01.007","url":null,"abstract":"<div><p>L-type amino acid transporter 1 (LAT1, SLC7A5) is upregulated in various cancers and associated with disease progression. Nanvuranlat (Nanv; JPH203, KYT-0353), a selective LAT1 inhibitor, suppresses the uptake of large neutral amino acids required for rapid growth and proliferation of cancer cells. Previous studies have suggested that the inhibition of LAT1 by Nanv induces the cell cycle arrest at G0/G1 phase, although the underlying mechanisms remain unclear. Using pancreatic cancer cells arrested at the restriction check point (R) by serum deprivation, we found that the Nanv drastically suppresses the G0/G1-S transition after release. This blockade of the cell cycle progression was accompanied by a sustained activation of p38 mitogen-activated protein kinase (MAPK) and subsequent phosphorylation-dependent proteasomal degradation of cyclin D1. Isoform-specific knockdown of p38 MAPK revealed the predominant contribution of p38α. Proteasome inhibitors restored the cyclin D1 amount and released the cell cycle arrest caused by Nanv. The increased phosphorylation of p38 MAPK and the decrease of cyclin D1 were recapitulated in xenograft tumor models treated with Nanv. This study contributes to delineating the pharmacological activities of LAT1 inhibitors as anti-cancer agents and provides significant insights into the molecular basis of the amino acid-dependent cell cycle checkpoint at G0/G1 phase.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 3","pages":"Pages 182-191"},"PeriodicalIF":3.5,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000070/pdfft?md5=2f3d063a5999027f0f35bd1486d145ea&pid=1-s2.0-S1347861324000070-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139645596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss of the sustained antidepressant-like effect of (2R,6R)-hydroxynorketamine in NMDA receptor GluN2D subunit knockout mice NMDA受体GluN2D亚基敲除小鼠体内(2R,6R)-羟基炔诺酮乙胺持续抗抑郁样作用的丧失

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-01-26 DOI: 10.1016/j.jphs.2024.01.008

Aimi Yamagishi , Yuiko Ikekubo , Masayoshi Mishina , Kazutaka Ikeda , Soichiro Ide

{"title":"Loss of the sustained antidepressant-like effect of (2R,6R)-hydroxynorketamine in NMDA receptor GluN2D subunit knockout mice","authors":"Aimi Yamagishi , Yuiko Ikekubo , Masayoshi Mishina , Kazutaka Ikeda , Soichiro Ide","doi":"10.1016/j.jphs.2024.01.008","DOIUrl":"10.1016/j.jphs.2024.01.008","url":null,"abstract":"<div><p>Ketamine, an <em>N</em>-methyl-<span>d</span>-aspartate (NMDA) receptor antagonist, has attracted attention for its acute and sustained antidepressant effects in patients with depression. Hydroxynorketamine (HNK), a metabolite of ketamine, exerts antidepressant effects without exerting ketamine's side effects and has attracted much attention in recent years. However, the detailed pharmacological mechanism of action of HNK remains unclear. We previously showed that the GluN2D NMDA receptor subunit is important for sustained antidepressant-like effects of (<em>R</em>)-ketamine. Therefore, we investigated whether the GluN2D subunit is involved in antidepressant-like effects of (2<em>R</em>,6<em>R</em>)-HNK and (2<em>S</em>,6<em>S</em>)-HNK. Treatment with (2<em>R</em>,6<em>R</em>)-HNK but not (2<em>S</em>,6<em>S</em>)-HNK exerted acute and sustained antidepressant-like effects in the tail-suspension test in wildtype mice. Interestingly, sustained antidepressant-like effects of (2<em>R</em>,6<em>R</em>)-HNK were abolished in GluN2D-knockout mice, whereas acute antidepressant-like effects were maintained in GluN2D-knockout mice. When expression levels of GluN2A and GluN2B subunits were evaluated, a decrease in GluN2B protein expression in the nucleus accumbens was found in stressed wildtype mice but not in stressed GluN2D-knockout mice. These results suggest that the GluN2D subunit and possibly the GluN2B subunit are involved in the sustained antidepressant-like effect of (2<em>R</em>,6<em>R</em>)-HNK.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 3","pages":"Pages 203-208"},"PeriodicalIF":3.5,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000082/pdfft?md5=00ea33238b3934dd3830799218515da1&pid=1-s2.0-S1347861324000082-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139589450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sulconazole induces pyroptosis promoted by interferon-γ in monocyte/macrophage lineage cells 磺康唑在单核细胞/巨噬细胞系细胞中诱导由干扰素-γ促进的脓毒症

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-01-24 DOI: 10.1016/j.jphs.2024.01.006

Shiori Miyawaki, Atsushi Sawamoto, Satoshi Okuyama, Mitsunari Nakajima

{"title":"Sulconazole induces pyroptosis promoted by interferon-γ in monocyte/macrophage lineage cells","authors":"Shiori Miyawaki, Atsushi Sawamoto, Satoshi Okuyama, Mitsunari Nakajima","doi":"10.1016/j.jphs.2024.01.006","DOIUrl":"10.1016/j.jphs.2024.01.006","url":null,"abstract":"<div><p>Imidazole derivatives are commonly used as antifungal agents. Here, we aimed to investigate the functions of imidazole derivatives on macrophage lineage cells. We assessed the expression levels of inflammatory cytokines in mouse monocyte/macrophage lineage (RAW264.7) cells. All six imidazole derivatives examined, namely ketoconazole, sulconazole, isoconazole, luliconazole, clotrimazole, and bifonazole, reduced the expression levels of inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-α, after induction by lipopolysaccharide (LPS) in RAW264.7 cells. These imidazole derivatives also induced cell death in RAW264.7 cells, regardless of the presence or absence of LPS. Since the cell death was characteristic in morphology, we investigated the mode of the cell death. An imidazole derivative, sulconazole, induced gasdermin D degradation together with caspase-11 activation, namely, pyroptosis in RAW264.7 cells and peritoneal macrophages. Furthermore, priming with interferon-γ promoted sulconazole-induced pyroptosis in RAW264.7 cells and macrophages and reduced the secretion of the inflammatory cytokine, IL-1β, from sulconazole-treated macrophages. Our results suggest that imidazole derivatives suppress inflammation by inducing macrophage pyroptosis, highlighting their modulatory potential for inflammatory diseases.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 3","pages":"Pages 166-174"},"PeriodicalIF":3.5,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000069/pdfft?md5=02ad9073820dcbec5a07db633c872dfc&pid=1-s2.0-S1347861324000069-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139553810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The inhibitory effect of DIF-3 on polyinosinic–polycytidylic acid-induced innate immunity activation in human cerebral microvascular endothelial cells DIF-3 对聚肌苷酸诱导的人脑微血管内皮细胞先天免疫激活的抑制作用

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-01-17 DOI: 10.1016/j.jphs.2024.01.005

Ryusei Araya , Shihu Men , Yoshinori Uekusa , Zaiqiang Yu , Haruhisa Kikuchi , Kazuyuki Daitoku , Masahito Minakawa , Shogo Kawaguchi , Ken-Ichi Furukawa , Yoshiteru Oshima , Tadaatsu Imaizumi , Kazuhiko Seya

{"title":"The inhibitory effect of DIF-3 on polyinosinic–polycytidylic acid-induced innate immunity activation in human cerebral microvascular endothelial cells","authors":"Ryusei Araya , Shihu Men , Yoshinori Uekusa , Zaiqiang Yu , Haruhisa Kikuchi , Kazuyuki Daitoku , Masahito Minakawa , Shogo Kawaguchi , Ken-Ichi Furukawa , Yoshiteru Oshima , Tadaatsu Imaizumi , Kazuhiko Seya","doi":"10.1016/j.jphs.2024.01.005","DOIUrl":"10.1016/j.jphs.2024.01.005","url":null,"abstract":"<div><p>For the treatment and prevention of autoinflammatory diseases, it is essential to develop the drug, regulating the innate immune system. Although differentiation-inducing factor (DIF) derivatives, extracted from the cellular slime mold, <em>Dictyostelium discoideum</em>, exhibit immunomodulatory effects, their effects on the regulation of innate immunity in brain are unknown. In this study, we used the human cerebral microvascular endothelial cell line, hCMEC/D3, to investigate the effects of DIF derivatives on the generation of C-X-C motif chemokine (CXCL) 10 and interferon (IFN)-β induced by polyinosinic–polycytidylic acid (poly IC). DIF-3 (1–10 μM), but not DIF-1 and DIF-2, dose-dependently inhibited the biosynthesis of not only CXCL10 but also CXCL16 and C–C motif chemokine 2 induced by poly IC. DIF-3 also strongly decreased IFN-β mRNA expression and protein release from the cells induced by poly IC through the prohibition of p65, a subtype of NF-ĸB, not interferon regulatory transcription factor 3 phosphorylation. In the docking simulation study, we confirmed that DIF-3 had a high affinity to p65. These results suggest that DIF-3 regulates the innate immune system by inhibiting TLR3/IFN-β signaling axis through the NF-ĸB phosphorylation inhibition.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 3","pages":"Pages 157-165"},"PeriodicalIF":3.5,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000057/pdfft?md5=c67009b6c8242c11c621726df47b77d3&pid=1-s2.0-S1347861324000057-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139497770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic effects of the alkaline extract of leaves of Sasa sp. and elucidation of its mechanism in acute kidney injury 莎莎叶碱性提取物对急性肾损伤的治疗作用及其机制的阐明

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-01-11 DOI: 10.1016/j.jphs.2024.01.004

Mizuki Sano , Yutaro Koseki , Keita Shibata , Tomohiro Fujisawa , Koji Nobe

{"title":"Therapeutic effects of the alkaline extract of leaves of Sasa sp. and elucidation of its mechanism in acute kidney injury","authors":"Mizuki Sano , Yutaro Koseki , Keita Shibata , Tomohiro Fujisawa , Koji Nobe","doi":"10.1016/j.jphs.2024.01.004","DOIUrl":"10.1016/j.jphs.2024.01.004","url":null,"abstract":"<div><p>Acute kidney injury (AKI), a common complication in hospitalized patients, is associated with high morbidity and mortality rates. However, there are currently no approved or effective therapeutics for AKI. AKI is primarily caused by ischemia/reperfusion (I/R) injury, with oxidative stress from reactive oxygen species (ROS) being a major contributor. This study aimed to evaluate the efficacy of an alkaline extract of the leaves of <em>Sasa</em> sp. (SE) using mouse renal I/R injury and hypoxia/reoxygenation (H/R) models in NRK-52E cells. Renal function parameters were measured, and histopathological evaluations were performed to assess the efficacy of SE. In addition, to determine the mechanisms underlying the effects of SE on renal I/R injury, its effects on malondialdehyde (MDA) of oxidative stress and interleukin (IL)-6 and IL-1β of inflammatory cytokines were evaluated. SE (0.03, 0.3, and 3 g/kg) improved renal function in a dose-dependent manner. In addition, SE ameliorated tubular injury and, reduced IL-6, IL-1β and MDA. Also, SE ameliorated cell death, ROS production, and inflammatory cytokine production in H/R-exposed NRK-52E cells. SE showed antioxidant and anti-inflammatory activities in the AKI. These results indicate the potential of SE as a medicinal compound for the prevention and treatment of AKI.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 3","pages":"Pages 148-156"},"PeriodicalIF":3.5,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000045/pdfft?md5=23b688b6714e82e6fa4024464d0a9195&pid=1-s2.0-S1347861324000045-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139422731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuronal activation of nucleus accumbens by local methamphetamine administration induces cognitive impairment through microglial inflammation in mice 小鼠局部注射甲基苯丙胺激活伏隔核的神经元，通过小胶质细胞炎症诱发认知障碍

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-01-09 DOI: 10.1016/j.jphs.2023.12.003

Yuka Kusui, Naotaka Izuo, Reika Tokuhara, Takashi Asano, Atsumi Nitta

{"title":"Neuronal activation of nucleus accumbens by local methamphetamine administration induces cognitive impairment through microglial inflammation in mice","authors":"Yuka Kusui, Naotaka Izuo, Reika Tokuhara, Takashi Asano, Atsumi Nitta","doi":"10.1016/j.jphs.2023.12.003","DOIUrl":"10.1016/j.jphs.2023.12.003","url":null,"abstract":"<div><p>More than half of methamphetamine (METH) users present with cognitive impairment, making it difficult for them to reintegrate into society. However, the mechanisms of METH-induced cognitive impairment remain unclear. METH causes neuronal hyperactivation in the nucleus accumbens (NAc) by aberrantly releasing dopamine, which triggers dependence. In this study, to clarify the involvement of hyperactivation of NAc in METH-induced cognitive impairment, mice were locally microinjected with METH into NAc (mice with METH (NAc)) and investigated their cognitive phenotype. Mice with METH (NAc) exhibited cognitive dysfunction in behavioral analyses and decreased long-term potentiation in the hippocampus, with NAc activation confirmed by expression of FosB, a neuronal activity marker. In the hippocampus of mice with METH (NAc), activated microglia, but not astroglia, and upregulated microglia-related genes, <em>Il1b</em> and <em>C1qa</em> were observed. Finally, administration of minocycline, a tetracycline antibiotic with suppressive effect on microglial activation, to mice with METH (NAc) ameliorated cognitive impairment and synaptic dysfunction by suppressing the increased expression of <em>Il1b</em> and <em>C1qa</em> in the hippocampus. In conclusion, activation of NAc by injection of METH into NAc elicited cognitive impairment by facilitating immune activation in mice. This study suggests that immunological intervention could be a therapeutic strategy for addiction-related cognitive disturbances.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 3","pages":"Pages 127-138"},"PeriodicalIF":3.5,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000713/pdfft?md5=d95bb2fc4d25ec32212485dec23607e7&pid=1-s2.0-S1347861323000713-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139414616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blockade of vasoactive intestinal peptide receptor 2 (VIPR2) signaling suppresses cyclin D1-dependent cell-cycle progression in MCF-7 cells 阻断血管活性肠肽受体 2 (VIPR2) 信号传导可抑制 MCF-7 细胞中依赖细胞周期蛋白 D1 的细胞周期进程

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-01-05 DOI: 10.1016/j.jphs.2024.01.002

Satoshi Asano , Ami Ono , Kaede Baba , Teru Uehara , Kotaro Sakamoto , Atsuko Hayata-Takano , Takanobu Nakazawa , Souichi Yanamoto , Kotaro Tanimoto , Hitoshi Hashimoto , Yukio Ago

{"title":"Blockade of vasoactive intestinal peptide receptor 2 (VIPR2) signaling suppresses cyclin D1-dependent cell-cycle progression in MCF-7 cells","authors":"Satoshi Asano , Ami Ono , Kaede Baba , Teru Uehara , Kotaro Sakamoto , Atsuko Hayata-Takano , Takanobu Nakazawa , Souichi Yanamoto , Kotaro Tanimoto , Hitoshi Hashimoto , Yukio Ago","doi":"10.1016/j.jphs.2024.01.002","DOIUrl":"10.1016/j.jphs.2024.01.002","url":null,"abstract":"<div><p>Vasoactive intestinal peptide (VIP) receptor 2 (VIPR2) is a G protein-coupled receptor that binds to Gαs, Gαi, and Gαq proteins to regulate various downstream signaling molecules, such as protein kinase A (PKA), phosphatidylinositol 3-kinase (PI3K), and phospholipase C. In this study, we examined the role of VIPR2 in cell cycle progression. KS-133, a newly developed VIPR2-selective antagonist peptide, attenuated VIP-induced cell proliferation in MCF-7 cells. The percentage of cells in the S-M phase was decreased in MCF-7 cells treated with KS-133. KS-133 in the presence of VIP decreased the phosphorylation of extracellular signal-regulated kinase (ERK), AKT, and glycogen synthase kinase-3β (GSK3β), resulting in a decrease in cyclin D1 levels. In MCF-7 cells stably-expressing VIPR2, KS-133 decreased PI3K activity and cAMP levels. Treatment with the ERK-specific kinase (MEK) inhibitor U0126 and the class I PI3K inhibitor ZSTK474 decreased the percentage of cells in the S phase. KS-133 reduced the percentage of cells in the S phase more than treatment with U0126 or ZSTK474 alone and did not affect the effect of the mixture of these inhibitors. Our findings suggest that VIPR2 signaling regulates cyclin D1 levels through the cAMP/PKA/ERK and PI3K/AKT/GSK3β pathways, and mediates the G1/S transition to control cell proliferation.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 3","pages":"Pages 139-147"},"PeriodicalIF":3.5,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000021/pdfft?md5=d75ede11b499c701adc03b6494bc3efd&pid=1-s2.0-S1347861324000021-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139102169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of P2Y6 receptor in the pathogenesis of cardiovascular and inflammatory diseases P2Y6 受体在心血管疾病和炎症性疾病发病机制中的作用

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-01-05 DOI: 10.1016/j.jphs.2024.01.003

Kazuhiro Nishiyama

{"title":"The role of P2Y6 receptor in the pathogenesis of cardiovascular and inflammatory diseases","authors":"Kazuhiro Nishiyama","doi":"10.1016/j.jphs.2024.01.003","DOIUrl":"10.1016/j.jphs.2024.01.003","url":null,"abstract":"<div><p>The purinergic receptor P2Y<sub>6</sub> receptor (P2Y<sub>6</sub>R) is a member of the G protein-coupled receptors (GPCR) family. P2Y<sub>6</sub>R is widely expressed in various cell types and plays a critical role in physiological processes, where it is activated by extracellular uridine diphosphate (UDP) and mobilizes Ca<sup>2+</sup> via the G<sub>αq/11</sub> protein pathway. We have recently discovered the pathophysiological role of P2Y<sub>6</sub>R in cardiovascular and inflammatory diseases, including inflammatory bowel disease and non-alcoholic fatty liver disease. Furthermore, we uncovered the redox-dependent internalization of P2Y<sub>6</sub>R. In this review, we provide a comprehensive overview of the pathophysiological activity of P2Y<sub>6</sub>R in cardiovascular and inflammatory diseases. Additionally, we discuss the concept of atypical internalization control of GPCRs, which may be applied in the prevention and treatment of intestinal inflammation and cardiovascular remodeling.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 2","pages":"Pages 108-112"},"PeriodicalIF":3.5,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000033/pdfft?md5=247fd27157e9f44c7eecbc02e15a9785&pid=1-s2.0-S1347861324000033-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139102719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0