Journal of pharmacological sciences最新文献

Targeting TMEM16A ion channels suppresses airway hyperreactivity, inflammation, and remodeling in an experimental Guinea pig asthma model 在实验性几内亚猪哮喘模型中，靶向 TMEM16A 离子通道可抑制气道过度反应、炎症和重塑

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-10-28 DOI: 10.1016/j.jphs.2024.10.004

Jozef Mažerik , Eduard Gondáš , Matúš Dohál , Lukáš Smieško , Marta Jošková , Soňa Fraňová , Martina Šutovská

{"title":"Targeting TMEM16A ion channels suppresses airway hyperreactivity, inflammation, and remodeling in an experimental Guinea pig asthma model","authors":"Jozef Mažerik , Eduard Gondáš , Matúš Dohál , Lukáš Smieško , Marta Jošková , Soňa Fraňová , Martina Šutovská","doi":"10.1016/j.jphs.2024.10.004","DOIUrl":"10.1016/j.jphs.2024.10.004","url":null,"abstract":"<div><div>Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, inflammation, and remodeling. Calcium (Ca<sup>2+</sup>)-activated chloride (Cl<sup>−</sup>) channels, such as TMEM16A, are inferred to be involved in asthma. Therefore, the present study investigated the therapeutic potential of TMEM16A inhibition in a guinea pig model of ovalbumin (OVA)-induced allergic asthma. Guinea pigs were treated with a specific blocker, CaCCinh-A01 (10 μM), administered via inhalation. A significant reduction in cough reflex sensitivity and specific airway resistance was observed in animals treated with CaCCinh-A01, highlighting its potential to improve airway function. Despite a reduction in ciliary beating frequency (CBF), CaCCinh-A01 reduced airway mucus viscosity by decreasing the production of mucin-5AC (MUC5AC). The nonspecific reduction in the Th1/Th2 cytokine spectrum following CaCCinh-A01 treatment indicated the suppression of airway inflammation. Additionally, markers associated with airway remodeling were diminished, suggesting that CaCCinh-A01 may counteract structural changes in airway tissues. Therefore, inhibition appears to mitigate the pathological aspects of asthma, including airway hyperresponsiveness, inflammation, and remodeling. However, further studies are required to comprehensively evaluate the potential of TMEM16A as a therapeutic target for asthma.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552112","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

Glucosylceramide synthase inhibitor ameliorates chronic inflammatory pain 葡萄糖酰胺合成酶抑制剂可改善慢性炎症性疼痛

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-10-15 DOI: 10.1016/j.jphs.2024.10.003

Shun Watanabe , Misa Oyama , Takashi Iwai , Mitsuo Tanabe

引用次数: 0

Analgesic effect of Keishinieppiittokajutsubu on low barometric pressure-induced pain response in arthritic model rats Keishinieppiittokajutsubu 对低气压引起的关节炎模型大鼠疼痛反应的镇痛效果

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-10-09 DOI: 10.1016/j.jphs.2024.10.002

Yuki Kurauchi , Kana Inoue , Tomoka Kawakami , Manami Ueda , Tomoko Yamaguchi , Junji Akaki , Masahiko Komorisono , Hiroshi Katsuki

引用次数: 0

TND1128, a 5-deazaflavin derivative with auto-redox ability, facilitates polarization of mitochondrial membrane potential (ΔΨm) and on-demand ATP synthesis in mice brain slices TND1128是一种具有自动氧化还原能力的5-去氮黄素衍生物，可促进小鼠脑切片线粒体膜电位（ΔΨm）的极化和按需合成 ATP

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-10-09 DOI: 10.1016/j.jphs.2024.10.001

Nanae Takahashi , Tomohisa Nagamatsu , Norio Akaike , Yoshihisa Kudo

{"title":"TND1128, a 5-deazaflavin derivative with auto-redox ability, facilitates polarization of mitochondrial membrane potential (ΔΨm) and on-demand ATP synthesis in mice brain slices","authors":"Nanae Takahashi , Tomohisa Nagamatsu , Norio Akaike , Yoshihisa Kudo","doi":"10.1016/j.jphs.2024.10.001","DOIUrl":"10.1016/j.jphs.2024.10.001","url":null,"abstract":"<div><div>TND1128, a 5-deazaflavin derivative, is a drug with self-redox ability. We examined the effect of TND1128 on the level of mitochondrial membrane potential (ΔΨ<sub>m</sub>), which is the most critical motive power for the biosynthesis of ATP. We prepared brain slices from mice pretreated with TND1128 (0.1–10 mg/kg, intraperitoneally) and detected ΔΨ<sub>m</sub> level with JC-1, a fluorescence ΔΨ<sub>m</sub> indicator. We further examined the depolarization of ΔΨ<sub>m</sub> under 5-min exposure to 25 mM KCl-ACSF (25K-ACSF), which activated neuronal voltage-dependent Ca<sup>2+</sup> channels. We evaluated the effect of TND1128 by using the inverse number of the ΔΨ<sub>m</sub> value as the ATP synthesis index (ASI). The level of ΔΨ<sub>m</sub> increased significantly by 24-h pretreatment with TND1128 (10 mg/kg), and significantly higher depolarization of the ΔΨ<sub>m</sub> was observed with 25K-ACSF exposure than in non-treated control. We found a significant decrease in 25K-ACSF induced [Ca<sup>2+</sup>]<sub>c</sub> and [Ca<sup>2+</sup>]<sub>m</sub> levels in the TND1128-pretreated preparations. We confirmed the dose and time-dependent facilitatory effects of TND1128 on the ASI. This study suggested that TND1128 could be incorporated into the TCA cycle and electron transfer chains to facilitate the polarization of ΔΨ<sub>m</sub> and activate on-demand ATP synthesis. TND1128 might rescue neurons in various brain diseases caused by energy defects. (198)</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432368","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

Involvement of Cav3.2 T-type Ca2+ channels and cystathionine-β-synthase in colitis-related visceral hypersensitivity in mice Cav3.2 T 型 Ca2+ 通道和胱硫醚-β-合成酶参与小鼠结肠炎相关的内脏超敏反应

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-09-21 DOI: 10.1016/j.jphs.2024.09.003

Maho Tsubota , Yuriko Iba , Tsukasa Hatakeyama , Myu Honda , Yoshihito Kasanami , Fumiko Sekiguchi , Atsushi Kawase , Takuya Okada , Naoki Toyooka , Atsufumi Kawabata

引用次数: 0

Role of CD34 in calcification of human aortic valve interstitial cells from patients with aortic valve stenosis CD34 在主动脉瓣狭窄患者主动脉瓣间质细胞钙化中的作用

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-09-12 DOI: 10.1016/j.jphs.2024.09.002

Shihu Men , Zaiqiang Yu , Xu Liu , Kazuyuki Daitoku , Mayuki Tachizaki , Shogo Kawaguchi , Tadaatsu Imaizumi , Masahito Minakawa , Kazuhiko Seya

{"title":"Role of CD34 in calcification of human aortic valve interstitial cells from patients with aortic valve stenosis","authors":"Shihu Men , Zaiqiang Yu , Xu Liu , Kazuyuki Daitoku , Mayuki Tachizaki , Shogo Kawaguchi , Tadaatsu Imaizumi , Masahito Minakawa , Kazuhiko Seya","doi":"10.1016/j.jphs.2024.09.002","DOIUrl":"10.1016/j.jphs.2024.09.002","url":null,"abstract":"<div><p>Various osteogenic factors are involved in ectopic human aortic valve calcification; however, the key cell species involved in calcification remains unclear. In a previous study, we reported that mesenchymal stem (CD73, 90, 105) and endothelial (VEGFR2) cell markers are positive in almost all human aortic valve interstitial cells (HAVICs) obtained from a patient with calcified aortic valve stenosis (CAVS). Further, CD34-negative HAVICs are highly sensitive to calcification stimulations. Here, we aimed to pathophysiologically clarify the role of CD34 in HAVICs obtained from individual patients with severe CAVS. A DNA microarray between CD34-positive and CD34-negative HAVICs, separated by fluorescence-activated cell sorting, indicated that tenascin X (TNX) mRNA expression significantly decreased in CD34-negative cells. Furthermore, the inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1β significantly downregulated CD34 expression in HAVICs. TGF-β, a key cytokine of endothelial-mesenchymal transition, did not affect HAVIC calcification. CD34 overexpression strongly inhibited TNF-α- and IL-1β-induced calcification and maintained TNX mRNA expression. These results suggest one possibility that CD34 is an inhibitory regulator of valve calcification. Furthermore, TNF-α- and IL-1β-induced CD34 downregulation in HAVICs contributes to HAVIC calcification by downregulating TNX protein expression.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000653/pdfft?md5=b79f6f3c23bb64cde0cdbebb1b3c1e17&pid=1-s2.0-S1347861324000653-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233063","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

Evaluation of inhibitory actions of antidepressants on muscarinic receptors assessed by a binding assay in the mouse cerebral neocortex 通过小鼠大脑新皮层结合试验评估抗抑郁药对毒蕈碱受体的抑制作用

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-09-11 DOI: 10.1016/j.jphs.2024.09.001

Keisuke Obara, Yuki Usami, Risa Okamoto, Kento Yoshioka, Yoshio Tanaka

引用次数: 0

Emodin alleviates lung injury via the miR-217-5p/Sirt1 axis in rats with severe acute pancreatitis 大黄素通过 miR-217-5p/Sirt1 轴减轻重症急性胰腺炎大鼠的肺损伤

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-08-30 DOI: 10.1016/j.jphs.2024.08.007

Zhihang Zhang , Yalan Luo , Xijing Zhuang , Haifeng Gao , Qi Yang , Hailong Chen

{"title":"Emodin alleviates lung injury via the miR-217-5p/Sirt1 axis in rats with severe acute pancreatitis","authors":"Zhihang Zhang , Yalan Luo , Xijing Zhuang , Haifeng Gao , Qi Yang , Hailong Chen","doi":"10.1016/j.jphs.2024.08.007","DOIUrl":"10.1016/j.jphs.2024.08.007","url":null,"abstract":"<div><p>Acute lung injury (ALI) is closely related to high mortality in severe acute pancreatitis (SAP). This study unveils the therapeutic effect and mechanism of miR-217-5p on SAP-associated ALI. The miR-217-5p RNA expression was significantly up-regulated in lipopolysaccharide (LPS)-stimulated primary rat alveolar epithelial type II cells (AEC II) and sodium taurocholate-treated pancreas and lung in SAP rats. miR-217 inhibition protected AEC II from LPS-induced damage by inhibiting apoptosis and reducing the TNF-α, IL-6, and ROS levels. miR-217 inhibition suppressed apoptosis and alleviated mitochondrial damage through mitochondria-mediated apoptotic pathway <em>in vitro</em>. Sirt1 is a direct target of miR-217-5p. Dual-luciferase reporter assay confirmed the binding of miR-217-5p to Sirt1 mRNA 3′-UTR. The rescue experiment identified that the anti-apoptotic, anti-inflammatory, and anti-oxidative effects of miR-217 inhibition were mediated by Sirt1 <em>in vitro</em>. Emodin (EMO) protected AEC II from LPS-induced damage and alleviated pancreatic and lung tissue injuries. EMO exerted similar effects as miR-217 inhibition <em>in vitro</em> and <em>in vivo</em>. The effects of EMO were abolished by miR-217 overexpression. In conclusion, miR-217-5p inhibition exerts protective effects on SAP-ALI <em>in vitro</em> and <em>in vivo</em> by repressing apoptosis, inflammation, and oxidative stress through Sirt1 activation. EMO protects against lung injuries in SAP-associated ALI rats through miR-217-5p/Sirt1 axis.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132400063X/pdfft?md5=3d53035ef4c6f969c6fe0d4f04792bd1&pid=1-s2.0-S134786132400063X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167512","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

Effect of antiemetics on zolbetuximab-induced gastric injury and emesis in ferrets 止吐药对唑贝妥昔单抗诱发雪貂胃损伤和呕吐的影响

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-08-26 DOI: 10.1016/j.jphs.2024.08.005

Fumitaka Kinugasa , Satoru Kajikawa , Jane Weng , Tohru Ugawa , Hiroshi Fushiki , Yosuke Yamanaka , Masanori Nagata , Gillian Haggerty , Shinobu Akuzawa , Taisuke Nakazawa , Hiroshi Suzuki , Taiji Sawamoto

{"title":"Effect of antiemetics on zolbetuximab-induced gastric injury and emesis in ferrets","authors":"Fumitaka Kinugasa , Satoru Kajikawa , Jane Weng , Tohru Ugawa , Hiroshi Fushiki , Yosuke Yamanaka , Masanori Nagata , Gillian Haggerty , Shinobu Akuzawa , Taisuke Nakazawa , Hiroshi Suzuki , Taiji Sawamoto","doi":"10.1016/j.jphs.2024.08.005","DOIUrl":"10.1016/j.jphs.2024.08.005","url":null,"abstract":"<div><p>Claudin-18 splice variant 2 (CLDN18.2), a tight junction protein, is a highly cell type–specific antigen that is expressed by differentiated gastric mucosa cells. The expression of CLDN18.2 in gastric mucosa cells may be retained upon malignant transformation and is displayed on the surface of several tumors, including gastric/gastroesophageal junction adenocarcinoma. Zolbetuximab is a genetically engineered, highly purified chimeric (mouse/human IgG1) antibody directed against CLDN18.2. Nausea and vomiting were observed as adverse events of zolbetuximab. To investigate the mechanism of nausea and vomiting in humans, we evaluated emesis (retching and vomiting) and conducted histopathologic assessment in ferrets after the administration of zolbetuximab. Emesis was frequently observed in all ferrets treated with zolbetuximab in the first hour after administration. Histopathologic assessment revealed the surface of the gastric mucosa was the primary site of emesis-associated tissue damage. The effect of antiemetics (dexamethasone, ondansetron, fosaprepitant, and olanzapine) on emesis induced by zolbetuximab was investigated. Fosaprepitant showed suppressive effects on emesis, and use of dexamethasone or concomitant use of fosaprepitant with other antiemetics tended to alleviate gastric tissue damage. The onset of emesis in humans receiving zolbetuximab may be associated with damage in the gastric mucosa, and antiemetics may mitigate gastrointestinal adverse events.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000616/pdfft?md5=9b59c0d1648aac137bdf955240f12ad2&pid=1-s2.0-S1347861324000616-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076865","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

Amitriptyline and duloxetine attenuate activities of superficial dorsal horn neurons in a rat reserpine-induced fibromyalgia model 阿米替林和度洛西汀可减轻利血平诱导的大鼠纤维肌痛模型中浅层背角神经元的活动

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-08-23 DOI: 10.1016/j.jphs.2024.08.006

Daisuke Uta , Katsuyuki Tsuboshima , Kazue Mizumura , Hisao Nishijo , Toru Taguchi

{"title":"Amitriptyline and duloxetine attenuate activities of superficial dorsal horn neurons in a rat reserpine-induced fibromyalgia model","authors":"Daisuke Uta , Katsuyuki Tsuboshima , Kazue Mizumura , Hisao Nishijo , Toru Taguchi","doi":"10.1016/j.jphs.2024.08.006","DOIUrl":"10.1016/j.jphs.2024.08.006","url":null,"abstract":"<div><p>Fibromyalgia (FM) is an intractable disease with a chief complaint of chronic widespread pain. Amitriptyline (AMI) and duloxetine (DLX), which are antidepressant drugs, have been reported to ameliorate pain in patients with FM and pain-related behaviors in several rodent models of FM. However, the mechanisms of action of AMI and DLX are not yet fully understood. Here, we examined the effects of these drugs on the responsiveness of superficial dorsal horn (SDH) neurons in the spinal cord, using a rat FM model developed by injecting a biogenic amine depleter (reserpine). Extracellular recordings of SDH neurons <em>in vivo</em> demonstrated that bath application of AMI and DLX at concentrations of 0.1–1.0 mM on the dorsal surface of the spinal cord markedly suppressed spontaneous discharge and von Frey filament-evoked mechanical firing in SDH neurons. The suppression induced by the drugs was noted in a concentration-dependent manner and the suppressive effects resolved after washing the spinal cord surface. These results show that SDH neurons are the site of action for AMI and DLX in a rat reserpine-induced FM model. Spinal mechanisms may underlie the therapeutic effects of these drugs in patients with FM.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000628/pdfft?md5=9e053b739e9dddd2bd8d1a990fd5cd41&pid=1-s2.0-S1347861324000628-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096895","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