Journal of pharmacological sciences最新文献_第3页

Inhibitory effects of γ-linolenic acid on contractile responses in pig coronary arteries: Possible involvement of prostanoid TP receptor inhibition γ-亚麻酸对猪冠状动脉收缩反应的抑制作用：可能与前列腺素TP受体抑制有关

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-12 DOI: 10.1016/j.jphs.2025.05.009

Keisuke Obara , Kento Yoshioka , Mikoto Ozawa, Haruki Kimura, Mayu Kiguchi, Yuri Nakao, Hinako Miyaji, Toma Yamashita, Noboru Saitoh, Yutaka Nakagome, Sakika Ichihara, Yoshio Tanaka

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Improved serotonin neuron-specific viral vectors applicable for optogenetic manipulation and recording 改良的5 -羟色胺神经元特异性病毒载体，适用于光遗传操作和记录

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-08 DOI: 10.1016/j.jphs.2025.05.008

Takuma Noguchi , Harune Hori , Koji Toda , Hisashi Shirakawa , Hitoshi Hashimoto , Kazuki Nagayasu

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Centrally administered prostaglandin E2 suppresses the micturition reflex in rats 中央给药前列腺素E2抑制大鼠排尿反射

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-07 DOI: 10.1016/j.jphs.2025.05.005

Takahiro Shimizu , Nobutaka Shimizu , Shun Tsubouchi , Mio Togo , Youichirou Higashi , Motoaki Saito

{"title":"Centrally administered prostaglandin E2 suppresses the micturition reflex in rats","authors":"Takahiro Shimizu , Nobutaka Shimizu , Shun Tsubouchi , Mio Togo , Youichirou Higashi , Motoaki Saito","doi":"10.1016/j.jphs.2025.05.005","DOIUrl":"10.1016/j.jphs.2025.05.005","url":null,"abstract":"<div><div>Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) facilitates the micturition reflex at the lower urinary tract and spinal cord levels. However, the roles of brain PGE<sub>2</sub> in reflex regulation remain unclear. Therefore, we aimed to investigate the effects of intracerebroventricularly administered PGE<sub>2</sub> on the micturition reflex. We further investigated whether the PGE<sub>2</sub>-induced responses were dependent on the sympathetic nervous system (SNS) and identified the brain E-prostanoid receptor subtypes (EP<sub>1</sub>–EP<sub>4</sub>) involved in PGE<sub>2</sub>-induced effects. Intracerebroventricularly administered PGE<sub>2</sub> (0.1, 0.3, or 1 nmol/rat) dose-dependently increased the intercontraction intervals (ICI) and threshold pressure required to induce micturition (TP) without altering maximal voiding pressure in urethane-anesthetized (0.8 g/kg, ip) male rats. PGE<sub>2</sub> (1 nmol/rat) significantly increased the mean blood pressure; 6-hydroxydopamine-induced chemical sympathectomy ameliorated this increase. In contrast, chemical sympathectomy had no significant effect on the PGE<sub>2</sub>-induced increases in ICI and TP. Intracerebroventricularly pretreated SC51322 (EP<sub>1</sub> receptor antagonist, 100 nmol/rat) and PF04418948 (EP<sub>2</sub> receptor antagonist, 100 nmol/rat), but not L-798106 (EP<sub>3</sub> receptor antagonist, 100 nmol/rat) or L-161982 (EP<sub>4</sub> receptor antagonist, 100 nmol/rat), significantly attenuated the PGE<sub>2</sub> (1 nmol/rat)-induced changes in ICI and TP. These results suggest that centrally administered PGE<sub>2</sub> suppresses the rat micturition reflex through brain EP<sub>1</sub> and EP<sub>2</sub> receptors, independent of SNS activation.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 231-237"},"PeriodicalIF":3.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Early neuromyelitis optica antibody-induced molecular changes in aquaporin 4 and associated proteins at astrocyte endfeet in murine brain tissues 早期视神经脊髓炎抗体诱导小鼠脑组织星形胶质细胞终足水通道蛋白4及相关蛋白的分子变化

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-07 DOI: 10.1016/j.jphs.2025.05.007

Yumi Yoshikawa , Masaki Tomioka , Yoichiro Abe , Masato Yasui , Mutsuo Nuriya

{"title":"Early neuromyelitis optica antibody-induced molecular changes in aquaporin 4 and associated proteins at astrocyte endfeet in murine brain tissues","authors":"Yumi Yoshikawa , Masaki Tomioka , Yoichiro Abe , Masato Yasui , Mutsuo Nuriya","doi":"10.1016/j.jphs.2025.05.007","DOIUrl":"10.1016/j.jphs.2025.05.007","url":null,"abstract":"<div><div>Neuromyelitis optica spectrum disorder (NMOSD) is characterized by the production of autoantibodies against aquaporin 4 (AQP4). Because NMOSD progressively causes irreversible and severe neurological damages, understanding the initial molecular changes induced by anti-AQP4 antibody binding is crucial for designing early interventions. However, knowledge about the effects of the antibodies before AQP4 loss in brain tissues is limited. Using acutely prepared mouse brain slices, we aimed to investigate the initial molecular impact of NMO model antibodies on AQP4 and its associated proteins. We employed two different types of NMO model antibodies, E5415A and E5415B; E5415A recognizes both M1 and M23 isoforms, whereas E5415B exclusively binds to M23. We found that E5415A but not E5415B disrupted the uniform perivascular localization of AQP4, leading to fragmentation. We further addressed the impact of these changes on AQP4-associated proteins and found that strong colocalizations between AQP4 and dystrophin-glycoprotein complex (DGC) components were preserved, even after AQP4 localization pattern became fragmented. Thus, our study reveals the initial molecular changes in the AQP4 channel at the astrocytic endfeet in response to NMO model antibodies and highlights the early pathological events occurring in NMOSD.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 212-218"},"PeriodicalIF":3.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A selective eukaryotic elongation factor 2 kinase inhibitor, A484954 lowered blood glucose in Zucker fatty diabetes mellitus rat A484954是一种选择性真核延伸因子2激酶抑制剂，可降低Zucker脂肪性糖尿病大鼠的血糖

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-07 DOI: 10.1016/j.jphs.2025.05.006

Ko Adachi, Tomoko Kodama, Kosuke Otani, Keito Sano, Asuka Sugiyama, Muneyoshi Okada, Hideyuki Yamawaki

{"title":"A selective eukaryotic elongation factor 2 kinase inhibitor, A484954 lowered blood glucose in Zucker fatty diabetes mellitus rat","authors":"Ko Adachi, Tomoko Kodama, Kosuke Otani, Keito Sano, Asuka Sugiyama, Muneyoshi Okada, Hideyuki Yamawaki","doi":"10.1016/j.jphs.2025.05.006","DOIUrl":"10.1016/j.jphs.2025.05.006","url":null,"abstract":"<div><div>Eukaryotic elongation factor 2 kinase (eEF2K) is a protein kinase, regulating peptide translation. Zucker fatty diabetes mellitus (ZFDM) rat is a recently developed obesity and type 2 diabetes animal model with a missense mutation (<em>fa</em>) in leptin receptor gene (<em>Lepr</em>). ZFDM-<em>Lepr</em><sup><em>fa/fa</em></sup> rats (Homo) develop obesity and type 2 diabetes, while ZFDM-<em>Lepr</em><sup><em>fa/+</em></sup> rats (Hetero) are normal. The aim of this study was to determine effects of A484954 on glucose metabolism in ZFDM rats. A484954 (2.5 mg/kg) or carboxymethyl cellulose (CMC; 0.5 %), a vehicle was injected intraperitoneally for 15 days in 17–19-week-old rats. Compared with Hetero CMC, in Homo CMC; 1) blood and urine glucose levels were significantly elevated, 2) Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was significantly elevated, 3) mRNA expression of sodium-glucose cotransporter (SGLT)2 in kidney tended to be elevated, while that of glucose transporter (GLUT)4 in vastus lateralis muscle decreased. Compared with Homo CMC, in Homo A484954; 1) blood glucose was significantly reduced, while urine glucose did not change, 2) HOMA-IR tended to decrease, 3) mRNA expression of SGLT2 in the kidney and GLUT4 in the muscle did not change. This study demonstrates for the first time that A484954 induces hypoglycemic effects in Homo partly via preventing insulin resistance.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 270-275"},"PeriodicalIF":3.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ginkgolide B inhibits ferroptosis in PC12 cells and ameliorates the oxidative stress in spinal cord injury through activating Nrf2 signaling pathway 银杏内酯B通过激活Nrf2信号通路抑制PC12细胞铁凋亡，改善脊髓损伤后的氧化应激

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-03 DOI: 10.1016/j.jphs.2025.05.004

Wei She , Wenji Ma , Tongtong Zhang , Xunian Wu , Jianfu Li , Xingyong Li

{"title":"Ginkgolide B inhibits ferroptosis in PC12 cells and ameliorates the oxidative stress in spinal cord injury through activating Nrf2 signaling pathway","authors":"Wei She , Wenji Ma , Tongtong Zhang , Xunian Wu , Jianfu Li , Xingyong Li","doi":"10.1016/j.jphs.2025.05.004","DOIUrl":"10.1016/j.jphs.2025.05.004","url":null,"abstract":"<div><div>Spinal cord injury (SCI) commonly leads to loss of motor and sensory function and results in huge socioeconomic burden, and it triggers numerous secondary pathological events, including oxidative stress and ferroptosis. This study investigates the therapeutic potential of Ginkgolide B (GB), a neuroprotective compound derived from <em>Ginkgo biloba</em>, in mitigating SCI by targeting on ferroptosis. By using Erastin-induced ferroptosis in PC12 cells and a rat contusion SCI model, the present study demonstrated that GB significantly improved locomotor recovery, reduced neuronal loss, and attenuated histopathological damage. Mechanistically, GB suppressed ferroptosis markers, including elevated iron content, lipid peroxidation, and ACSL4, while restoring the expression of GPX4 and xCT. Crucially, GB enhanced nuclear translocation of Nrf2, upregulating downstream antioxidants and ferroptosis-related genes (HO-1 and NQO1). Notably, the functions of GB were abolished after utilization of Nrf2 signaling inhibitor ML385 which revealed the role of GB on recovery of SCI was highly related to the activation of Nrf2 signaling. These findings reveal that GB alleviates SCI by inhibiting ferroptosis through Nrf2 activation, positioning it as a promising therapeutic agent. This study elucidates a novel mechanism linking Nrf2 signaling to ferroptosis suppression in SCI and provides a translational framework for repurposing GB in SCI treatment.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 199-206"},"PeriodicalIF":3.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unravelling the effects of specific ingredients of kamishoyosan in reducing aggressive biting behavior in chronically isolated mice to inanimate objects 揭示神生糖特定成分在减少长期隔离小鼠对无生命物体的攻击性咬伤行为中的作用

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-02 DOI: 10.1016/j.jphs.2025.05.001

Kento Igarashi , Satoshi Kuchiiwa , Toshiko Kuchiiwa , Tomoaki Sato

{"title":"Unravelling the effects of specific ingredients of kamishoyosan in reducing aggressive biting behavior in chronically isolated mice to inanimate objects","authors":"Kento Igarashi , Satoshi Kuchiiwa , Toshiko Kuchiiwa , Tomoaki Sato","doi":"10.1016/j.jphs.2025.05.001","DOIUrl":"10.1016/j.jphs.2025.05.001","url":null,"abstract":"<div><div>Kamishoyosan (KSS) is a well-known traditional Japanese herbal medicine used to treat psychiatric symptoms, such as irritation. We previously reported that KSS decreases mouse aggressive biting behavior (ABB) to inanimate objects using the Aggression Response Meter, however, it was not revealed which ingredient of KSS is effective. In this study, we used real-time reverse transcriptase (RT) PCR to investigate the mRNA expression of 5-HT-related genes in SH-SY5Y cells cultured in a medium containing the ten individual herbal medicines in KSS. The cells treated with shakuyaku showed increase of tryptophan hydroxylase mRNA expression, whereas those cultured in a medium containing botanpi showed decreased monoamine oxidase A and B mRNA levels. We investigated the ABB of mice administered with <em>Paeonia lactiflora</em> (shakuyaku) or <em>Paeonia suffruticosa</em> (botanpi). We also examined the gene expression in cells treated with paeoniflorin (PF), a main active component in shakuyaku, and the ABB of PF-treated mice. We found that shakuyaku or PF administration reduced ABB in male and female mice, whereas botanpi treatment mitigated ABB only in males. WAY-100635, a 5-HT1A receptor antagonist, abolished ABB-reducing effect of shakuyaku and botanpi. These results suggest that shakuyaku and botanpi are activate ingredient to reduce ABB through activation on serotoninergic neurotransmission.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 259-269"},"PeriodicalIF":3.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pedunculoside regulates the differentiation of neural stem cells into neurons via the PI3K/AKT/GSK-3β pathway pedculloside通过PI3K/AKT/GSK-3β通路调控神经干细胞向神经元的分化

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-02 DOI: 10.1016/j.jphs.2025.05.002

Ruichen Jiang , Yuming Wang , Yanzhu Shen , Jiancheng Tang , Xiangsheng Tang , Haoning Ma , Ping Yi

{"title":"Pedunculoside regulates the differentiation of neural stem cells into neurons via the PI3K/AKT/GSK-3β pathway","authors":"Ruichen Jiang , Yuming Wang , Yanzhu Shen , Jiancheng Tang , Xiangsheng Tang , Haoning Ma , Ping Yi","doi":"10.1016/j.jphs.2025.05.002","DOIUrl":"10.1016/j.jphs.2025.05.002","url":null,"abstract":"<div><div>The aging population has increased neurodegenerative diseases, yet current therapies mostly relieve symptoms rather than halt disease progression. Neural stem cells (NSCs) are crucial in nervous system development and repair, and research on their proliferation and differentiation regulation is vital. This study aimed to explore the effect of pedunculoside (PE) on primary NSCs and its mechanism. NSCs from pregnant rats (E13 - E14) were cultured and studied using CCK - 8, EDU incorporation, immunofluorescence, Western blot, and molecular docking. Results showed PE significantly promoted NSC proliferation at 10 μM and 20 μM dose - dependently. It also enhanced neuronal differentiation, with increased TUJ - 1 and decreased GFAP. Molecular docking and Western blot revealed PE binds to PI3K, activates the PI3K/AKT/GSK-3β pathway, and promotes protein phosphorylation. The PI3K inhibitor experiment confirmed PE's effect on NSC differentiation is mediated by this pathway. This study provides evidence for PE's role in NSC research and advances nervous system disease treatment research.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 276-282"},"PeriodicalIF":3.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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A novel role of celecoxib in the inhibition of calcium-activated chloride channel ANO1 塞来昔布在抑制钙活化氯离子通道ANO1中的新作用

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-02 DOI: 10.1016/j.jphs.2025.05.003

Ping Zhou , Qinqin Li , Xiangyu Li , Yani Liu

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Erratum to “A novel lysophosphatidic acid receptor 1 antagonist with high brain penetrability has a curative effect in the empathic pain-related fibromyalgia model” [J Pharmacol Sci (2025) 139-142] “一种新型高脑穿透性溶血磷脂酸受体1拮抗剂在共情性疼痛相关纤维肌痛模型中的疗效”[J].药理杂志，2025,139-142。

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-04-29 DOI: 10.1016/j.jphs.2025.04.009

Hiroyuki Neyama , Naoki Dozono , Yasuka Sahara , Kenji Nishikawa , Hiroshi Ueda

引用次数: 0