Journal of pharmacological sciences最新文献_第7页

Opposite regulation by L-DOPA receptor GPR143 of the long and short forms of the dopamine D2 receptors 左旋多巴受体 GPR143 对多巴胺 D2 受体长短型的相反调节作用

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-07-30 DOI: 10.1016/j.jphs.2024.07.009

Rei Tajika , Daiki Masukawa , Masami Arai , Hiroyuki Nawa , Yoshio Goshima

{"title":"Opposite regulation by L-DOPA receptor GPR143 of the long and short forms of the dopamine D2 receptors","authors":"Rei Tajika , Daiki Masukawa , Masami Arai , Hiroyuki Nawa , Yoshio Goshima","doi":"10.1016/j.jphs.2024.07.009","DOIUrl":"10.1016/j.jphs.2024.07.009","url":null,"abstract":"<div><p>Dopamine (DA) D2 receptors (D2Rs) have 2 isoforms, a long form (D2L) and a short form (D2S). D2L is predominantly postsynaptic in the striatal medium spiny neurons and cholinergic interneurons. D2S is principally presynaptic autoreceptors in the nigrostriatal DA neurons. Recently, we demonstrated that L-3,4-dihydroxyphenylalanine (L-DOPA) augments D2L function through the coupling between D2L and GPR143, a receptor of L-DOPA that was originally identified as the gene product of ocular albinism 1. Here we show that GPR143 modifies the functions of D2L and D2S in an opposite manner. Haloperidol-induced catalepsy was attenuated in DA neuron-specific <em>Gpr143 gene</em>-deficient (<em>Dat-cre;Gpr143</em><sup><em>flox/y</em></sup>) mice, compared with wild-type (<em>Wt</em>) mice. Haloperidol increased in vivo DA release from the dorsolateral striatum, and this increase was augmented in <em>Gpr143</em><sup><em>-/y</em></sup> mice compared with <em>Wt</em> mice. A D2R agonist quinpirole-induced increase in the phosphorylation of GSK3β(pGSK3β(S9)) was enhanced in Chinese hamster ovary (CHO) cells coexpressing D2L and GPR143 compared with cells expressing D2L alone, while it was suppressed in cells coexpressing D2S and GPR143 compared with D2S alone, suggesting that GPR143 differentially modifies D2R functions depending on its isoforms of D2L and D2S.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 2","pages":"Pages 77-81"},"PeriodicalIF":3.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000549/pdfft?md5=0fada20c7d5bb425a552b2ffd56ab094&pid=1-s2.0-S1347861324000549-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141885296","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

Galantamine suppresses α-synuclein aggregation by inducing autophagy via the activation of α7 nicotinic acetylcholine receptors 加兰他敏通过激活α7烟碱乙酰胆碱受体诱导自噬抑制α-突触核蛋白聚集

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-07-30 DOI: 10.1016/j.jphs.2024.07.008

Sora Nozaki , Masanori Hijioka , Xiaopeng Wen , Natsumi Iwashita , Junya Namba , Yoshiaki Nomura , Aoi Nakanishi , Soichiro Kitazawa , Ryo Honda , Yuji O. Kamatari , Ryo Kitahara , Kenji Suzuki , Masatoshi Inden , Yoshihisa Kitamura

{"title":"Galantamine suppresses α-synuclein aggregation by inducing autophagy via the activation of α7 nicotinic acetylcholine receptors","authors":"Sora Nozaki , Masanori Hijioka , Xiaopeng Wen , Natsumi Iwashita , Junya Namba , Yoshiaki Nomura , Aoi Nakanishi , Soichiro Kitazawa , Ryo Honda , Yuji O. Kamatari , Ryo Kitahara , Kenji Suzuki , Masatoshi Inden , Yoshihisa Kitamura","doi":"10.1016/j.jphs.2024.07.008","DOIUrl":"10.1016/j.jphs.2024.07.008","url":null,"abstract":"<div><p>Synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are neurodegenerative disorders characterized by the aberrant accumulation of α-synuclein (α-syn). Although no treatment is effective for synucleinopathies, the suppression of α-syn aggregation may contribute to the development of numerous novel therapeutic targets. Recent research revealed that nicotinic acetylcholine (nACh) receptor activation has neuroprotective effects and promotes the degradation of amyloid protein by activating autophagy. In an <em>in vitro</em> human-derived cell line model, we demonstrated that galantamine, the nAChR allosteric potentiating ligand, significantly reduced the cell number of SH-SY5Y cells with intracellular Lewy body-like aggregates by enhancing the sensitivity of α<sub>7</sub>-nAChR. In addition, galantamine promoted autophagic flux, and prevented the formation of Lewy body-resembled aggregates. In an <em>in vivo</em> synucleinopathy mouse model, the propagation of α-syn aggregation in the cerebral cortex was inhibited by galantamine administration for 90 days. These results suggest that α<sub>7</sub>-nAChR is expected to be a novel therapeutic target, and galantamine is a potential agent for synucleinopathies.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 2","pages":"Pages 102-114"},"PeriodicalIF":3.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000537/pdfft?md5=aa744b27678a643ecef9a42546b74b7a&pid=1-s2.0-S1347861324000537-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141885299","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

Glucocorticoid-induced acute diuresis in rats in relation to the reduced renal expression of sodium-dependent cotransporter genes 糖皮质激素诱导的大鼠急性利尿与依赖钠的共转运体基因的肾表达减少有关

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-07-25 DOI: 10.1016/j.jphs.2024.07.005

Peiyan Zhao , Yoshiki Higashijima , Hiroko Sonoda , Rio Morinaga , Keito Uema , Akane Oguchi , Toshiyuki Matsuzaki , Masahiro Ikeda

{"title":"Glucocorticoid-induced acute diuresis in rats in relation to the reduced renal expression of sodium-dependent cotransporter genes","authors":"Peiyan Zhao , Yoshiki Higashijima , Hiroko Sonoda , Rio Morinaga , Keito Uema , Akane Oguchi , Toshiyuki Matsuzaki , Masahiro Ikeda","doi":"10.1016/j.jphs.2024.07.005","DOIUrl":"10.1016/j.jphs.2024.07.005","url":null,"abstract":"<div><p>Although several studies have shown that glucocorticoids exert diuretic effects in animals and humans, the underlying mechanism responsible for the acute diuretic effect remains obscure. Here we examined the mechanism in terms of gene-expression. We observed that glucocorticoids, including dexamethasone (Dex) and prednisolone (PSL), acutely induced diuresis in rats in a dose-dependent manner. Free water clearance values were negative after Dex or PSL treatment, similar to those observed after treatment with osmotic diuretics (furosemide and acetazolamide). Dex significantly increased the urinary excretion of sodium, potassium, chloride, glucose, and inorganic phosphorus. Renal microarray analysis revealed that Dex significantly altered the renal expression of genes related to transmembrane transport activity. The mRNA levels of sodium/phosphate (<em>NaPi-2a</em>/<em>Slc34a1</em>, <em>NaPi-2b/Slc34a2</em>, and <em>NaPi-2c</em>/<em>Slc34a3</em>) and sodium/glucose cotransporters (<em>Sglt2</em>/<em>Slc5a2</em>) were significantly reduced in the Dex-treated kidney, being negatively correlated with the urinary excretion of their corresponding solutes. Dex did not affect renal expression of the natriuretic peptide receptor 1 (<em>Npr1</em>) gene, or the expression, localization, and phosphorylation of aquaporin-2 (AQP2), a water channel protein. These findings suggest that the acute diuretic effects of glucocorticoids might be mediated by reduced expression of sodium-dependent cotransporter genes.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 2","pages":"Pages 115-124"},"PeriodicalIF":3.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000501/pdfft?md5=24cc0b983274fa57852681e87efd3633&pid=1-s2.0-S1347861324000501-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141844691","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

Inorganic sulfides prevent osimertinib-induced mitochondrial dysfunction in human iPS cell-derived cardiomyocytes 无机硫化物可预防奥西美替尼诱导的人类 iPS 细胞衍生心肌细胞线粒体功能障碍

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-07-23 DOI: 10.1016/j.jphs.2024.07.007

Moe Kondo , Yuya Nakamura , Yuri Kato , Akiyuki Nishimura , Mitsuhiro Fukata , Shohei Moriyama , Tomoya Ito , Keitaro Umezawa , Yasuteru Urano , Takaaki Akaike , Koichi Akashi , Yasunari Kanda , Motohiro Nishida

{"title":"Inorganic sulfides prevent osimertinib-induced mitochondrial dysfunction in human iPS cell-derived cardiomyocytes","authors":"Moe Kondo , Yuya Nakamura , Yuri Kato , Akiyuki Nishimura , Mitsuhiro Fukata , Shohei Moriyama , Tomoya Ito , Keitaro Umezawa , Yasuteru Urano , Takaaki Akaike , Koichi Akashi , Yasunari Kanda , Motohiro Nishida","doi":"10.1016/j.jphs.2024.07.007","DOIUrl":"10.1016/j.jphs.2024.07.007","url":null,"abstract":"<div><p>Despite the widespread recognition of the global concern regarding the onset of cardiovascular diseases in a significant number of patients following cancer treatment, definitive strategies for prevention and treatment remain elusive. In this study, we established systems to evaluate the influence of anti-cancer drugs on the quality control of mitochondria, pivotal for energy metabolism, using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor used for treatment in lung cancer, reportedly increases the risk of cardiovascular disease. However, its underlying mechanism is largely unknown. Here, we found that the treatment of hiPSC-CMs with osimertinib and doxorubicin, but not trastuzumab and cisplatin, revealed a concentration-dependent impairment of respiratory function accompanied by mitochondrial fission. We previously reported the significant role of sulfur metabolism in maintaining mitochondrial quality in the heart. Co-treatment with various inorganic sulfur donors (Na<sub>2</sub>S, Na<sub>2</sub>S<sub>2</sub>, Na<sub>2</sub>S<sub>3</sub>) alongside anti-cancer drugs demonstrated that Na<sub>2</sub>S attenuated the cardiotoxicity of osimertinib but not doxorubicin. Osimertinib decreased intracellular reduced sulfur levels, while Na<sub>2</sub>S treatment suppressed the sulfur leakage, suggesting its potential in mitigating osimertinib-induced cardiotoxicity. These results imply the prospect of inorganic sulfides, such as Na<sub>2</sub>S, as a seed for precision pharmacotherapy to alleviate osimertinib's cardiotoxic effects.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 2","pages":"Pages 69-76"},"PeriodicalIF":3.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000525/pdfft?md5=c0c8dd83d8cf944214165065772b20a2&pid=1-s2.0-S1347861324000525-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141771006","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

Activation of α7 nicotinic receptors attenuated hyperalgesia and anxiety induced by palatable obesogenic diet withdrawal 激活α7烟碱受体可减轻厌食性肥胖饮食戒断引起的痛觉过度和焦虑症

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-07-22 DOI: 10.1016/j.jphs.2024.07.006

Shakir D. AlSharari , Alaa A. Alameen , Fawzeyah S. Aldafiri , Yousif S. Ali , Musaad A. Alshammari , Youssef Sari , M.I. Damaj

{"title":"Activation of α7 nicotinic receptors attenuated hyperalgesia and anxiety induced by palatable obesogenic diet withdrawal","authors":"Shakir D. AlSharari , Alaa A. Alameen , Fawzeyah S. Aldafiri , Yousif S. Ali , Musaad A. Alshammari , Youssef Sari , M.I. Damaj","doi":"10.1016/j.jphs.2024.07.006","DOIUrl":"10.1016/j.jphs.2024.07.006","url":null,"abstract":"<div><p>Consumption of palatable food (PF) can alleviate anxiety, and pain in humans. Contrary, spontaneous withdrawal of long-term PF intake produces anxiogenic-like behavior and abnormal pain sensation, causing challenges to weight-loss diet and anti-obesity agents. Thus, we examined α7-nicotinic acetylcholine receptors (α7nAChR) involvement since it plays essential role in nociception and psychological behaviors.</p></div><div><h3>Methods</h3><p>Adult male C57BL/6 mice were placed on a Standard Chow (SC) alone or with PF on intermittent or continuous regimen for 6 weeks. Then, mice were replaced with normal SC (spontaneous withdrawal). Body weight, food intake, and calories intake with and without the obesogenic diet were measured throughout the study. During PF withdrawal, anxiety-like behaviors and pain sensitivity were measured with PNU-282987 (α7nAChR agonist) administration.</p></div><div><h3>Results</h3><p>Six weeks of SC + PF-intermittent and continuous paradigms produced a significant weight gain. PF withdrawal displayed hyperalgesia and anxiety-like behaviors. During withdrawal, PNU-282987 significantly attenuated hyperalgesia and anxiety-like behaviors.</p></div><div><h3>Conclusion</h3><p>The present study shows that a PF can increase food intake and body weight. Also, enhanced pain sensitivity and anxiety-like behavior were observed during PF withdrawal. α7nAChR activation attenuated anxiolytic-like behavior and hyperalgesia in PF abstinent mice. These data suggest potential therapeutic effects of targeting α7 nAChRs for obesity-withdrawal symptoms in obese subjects.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 2","pages":"Pages 86-101"},"PeriodicalIF":3.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000513/pdfft?md5=1b339559c66649a1de2d81eae2eadd91&pid=1-s2.0-S1347861324000513-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141771007","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 ZEB1 in mediating the protective effects of metformin on skeletal muscle atrophy ZEB1 在介导二甲双胍对骨骼肌萎缩的保护作用中的作用

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-07-18 DOI: 10.1016/j.jphs.2024.07.004

Peiyu Jia , Ji Che , Xiaoting Xie , Qi Han , Yantao Ma , Yong Guo , Yongjun Zheng

{"title":"The role of ZEB1 in mediating the protective effects of metformin on skeletal muscle atrophy","authors":"Peiyu Jia , Ji Che , Xiaoting Xie , Qi Han , Yantao Ma , Yong Guo , Yongjun Zheng","doi":"10.1016/j.jphs.2024.07.004","DOIUrl":"10.1016/j.jphs.2024.07.004","url":null,"abstract":"<div><p>Metformin is an important antidiabetic drug that has the potential to reduce skeletal muscle atrophy and promote the differentiation of muscle cells. However, the exact molecular mechanism underlying these functions remains unclear. Previous studies revealed that the transcription factor zinc finger E-box-binding homeobox 1 (ZEB1), which participates in tumor progression, inhibits muscle atrophy. Therefore, we hypothesized that the protective effect of metformin might be related to ZEB1. We investigated the positive effect of metformin on IL-1β-induced skeletal muscle atrophy by regulating ZEB1 <em>in vitro</em> and <em>in vivo</em>. Compared with the normal cell differentiation group, the metformin-treated group presented increased myotube diameters and reduced expression levels of atrophy-marker proteins. Moreover, muscle cell differentiation was hindered, when we artificially interfered with ZEB1 expression in mouse skeletal myoblast (C2C12) cells via ZEB1-specific small interfering RNA (si-ZEB1). In response to inflammatory stimulation, metformin treatment increased the expression levels of ZEB1 and three differentiation proteins, MHC, MyoD, and myogenin, whereas si-ZEB1 partially counteracted these effects. Moreover, marked atrophy was induced in a mouse model via the administration of lipopolysaccharide (LPS) to the skeletal muscles of the lower limbs. Over a 4-week period of intragastric administration, metformin treatment ameliorated muscle atrophy and increased the expression levels of ZEB1. Metformin treatment partially alleviated muscle atrophy and stimulated differentiation. Overall, our findings may provide a better understanding of the mechanism underlying the effects of metformin treatment on skeletal muscle atrophy and suggest the potential of metformin as a therapeutic drug.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 2","pages":"Pages 57-68"},"PeriodicalIF":3.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000495/pdfft?md5=a5ee22fb27dee55ffcead570eff1fba2&pid=1-s2.0-S1347861324000495-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141771008","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

l-DOPA receptor GPR143 inhibits neurite outgrowth via L-type calcium channels in PC12 cells l-DOPA 受体 GPR143 通过 PC12 细胞中的 L 型钙通道抑制神经元生长

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-07-06 DOI: 10.1016/j.jphs.2024.07.003

Miyu Inoue, Daiki Masukawa, Yoshio Goshima

引用次数: 0

Polyphyllin VII as a potential medication for targeting epithelial mesenchymal transitionin in thyroid cancer 聚卟啉 VII 是一种针对甲状腺癌上皮间质转化蛋白的潜在药物

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-07-06 DOI: 10.1016/j.jphs.2024.07.002

Qingqing Yu , Jinglin Chen , Chen Zhong , Le Yu , Yunhe Zhu , Xueyan Xi , Boyu Du

{"title":"Polyphyllin VII as a potential medication for targeting epithelial mesenchymal transitionin in thyroid cancer","authors":"Qingqing Yu , Jinglin Chen , Chen Zhong , Le Yu , Yunhe Zhu , Xueyan Xi , Boyu Du","doi":"10.1016/j.jphs.2024.07.002","DOIUrl":"10.1016/j.jphs.2024.07.002","url":null,"abstract":"<div><p>The need for novel anti-thyroid cancer (TC) medications is urgent due to the rising incidence and metastatic rates of malignant TC. In this study, we investigated the effect of Polyphyllin VII (PPVII) to TC cells, and explored their potential mechanism. B-CPAP and TPC-1 cells, were used to analyze the antitumor activity of PPVII by quantifying cell growth and metastasis as well as to study the effect on epithelial mesenchymal transition (EMT). The results showed that PPVII dramatically reduced the capacity of B-CPAP and TPC-1 cells to proliferate and migrate in a dose-response manner. Following PPVII treatment of TC cells, the expression levels of E-cadherin progressively increased and were higher than the control group, while the expression levels of EMT-related genes Vimentin, N-cadherin, Slug, Zeb-1, and Foxe1 gradually declined and were lower than the control group. It was proposed that PPVII might prevent TC from undergoing EMT. The Foxe1 gene was shown to be significantly expressed in TC, and a statistically significant variation in Foxe1 expression was observed across clinical stages of the disease, according to a bioinformatics database study. There was a strong link between the expression of the Foxe1 gene and the EMT-related gene. In the meantime, TC cells' expression of Foxe1 can be inhibited by PPVII. In conclusion, our results showed that PPVII may as a potential medication for targeting EMT in thyroid cancer.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 2","pages":"Pages 49-56"},"PeriodicalIF":3.0,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000471/pdfft?md5=d3fe5cae10081903a715d4c4842c8aef&pid=1-s2.0-S1347861324000471-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141714129","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

Combined antiallodynic effects of Neurotropin®–tramadol and Neurotropin®–mirogabalin in rats with L5-spinal nerve ligation 神经妥宾®-曲马多和神经妥宾®-米罗卡宾对脊神经L5结扎大鼠的联合镇痛作用

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-07-02 DOI: 10.1016/j.jphs.2024.07.001

Yukihiro Yoshimoto, Hisashi Okai, Hiroyoshi Namba, Kazuki Taguchi, Yoshiya Yamauchi, Jun Wakita, Ryohei Okazaki

{"title":"Combined antiallodynic effects of Neurotropin®–tramadol and Neurotropin®–mirogabalin in rats with L5-spinal nerve ligation","authors":"Yukihiro Yoshimoto, Hisashi Okai, Hiroyoshi Namba, Kazuki Taguchi, Yoshiya Yamauchi, Jun Wakita, Ryohei Okazaki","doi":"10.1016/j.jphs.2024.07.001","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.07.001","url":null,"abstract":"<div><p>We aimed to examine the efficacy of combination therapies of Neurotropin® with tramadol and Neurotropin with mirogabalin for neuropathic pain management. A neuropathic pain model (L5 spinal nerve ligation model: L5-SNL) using male Wistar rats was generated through tight ligation of the left fifth lumbar nerve using silk sutures. Mechanical allodynia was assessed using the 50% paw withdrawal threshold. The combined antiallodynic effects were evaluated using isobolographic analyses. Small intestinal transit was evaluated using the charcoal meal test, and motor coordination using the rota-rod test. Neurotropin (50–200 NU/kg, p.o.), tramadol (7.5–60 mg/kg, p.o.), and mirogabalin (3–30 mg/kg, p.o.) showed a dose-dependent antiallodynic effect in L5-SNL rats. The combined antiallodynic effects of Neurotropin and tramadol were additive or synergistic, whereas those of Neurotropin and mirogabalin were additive. Neurotropin (100–400 NU/kg, p.o.) did not affect the small intestinal transit, whereas tramadol (30–100 mg/kg, p.o.) significantly inhibited it. Neurotropin (100–400 NU/kg, p.o.) did not affect the walking time, whereas mirogabalin (10–100 mg/kg, p.o.) significantly decreased it. Neurotropin dose-dependently ameliorated mechanical allodynia in rats, and combination therapy with Neurotropin–tramadol or Neurotropin–mirogabalin may alleviate neuropathic pain without aggravating the adverse effects of tramadol and mirogabalin.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 1","pages":"Pages 30-37"},"PeriodicalIF":3.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132400046X/pdfft?md5=1f42974a74708cb6655b49c70f8527d9&pid=1-s2.0-S134786132400046X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542596","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

Alteration of reactivity in isolated mesenteric artery from Zucker fatty diabetes mellitus rats 扎克脂肪糖尿病大鼠离体肠系膜动脉反应性的改变

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-06-27 DOI: 10.1016/j.jphs.2024.06.006

Kosuke Otani, Naofumi Uemura, Hiroshi Funada, Tomoko Kodama, Muneyoshi Okada, Hideyuki Yamawaki

{"title":"Alteration of reactivity in isolated mesenteric artery from Zucker fatty diabetes mellitus rats","authors":"Kosuke Otani, Naofumi Uemura, Hiroshi Funada, Tomoko Kodama, Muneyoshi Okada, Hideyuki Yamawaki","doi":"10.1016/j.jphs.2024.06.006","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.06.006","url":null,"abstract":"<div><p>Obesity and diabetes are major risk factors for cardiovascular diseases. Zucker fatty diabetes mellitus (ZFDM) rats are novel animal model of obesity and type 2 diabetes. We have recently reported that blood pressure in ZFDM-<em>Lepr</em><sup>fa/fa</sup> (Homo) rats was normal, while blood adrenaline level and heart rate were lower than those in control ZFDM-<em>Lepr</em><sup>fa/+</sup> (Hetero) rats. Here, we compared the reactivity in isolated mesenteric artery between Hetero and Homo rats. Contraction induced by phenylephrine was increased, while relaxation induced by isoprenaline was decreased in Homo rats at 21–23 weeks old compared with those in Hetero rats. The mRNA expression for α<sub>1A</sub> but not β<sub>2</sub> adrenoreceptor in Homo rats was increased. Nitric oxide (NO)-mediated relaxation induced by acetylcholine was decreased, while the mRNA expression for endothelial NO synthase (eNOS) was rather increased in mesenteric artery from Homo rats. These findings for the first time revealed that in Homo rats with reduced plasma adrenaline, blood pressure could be maintained by enhancing vascular contractility induced by adrenaline through the increased α<sub>1</sub> adrenoceptor expression and the attenuated β<sub>2</sub> adrenoceptor signaling. Additionally, NO-mediated endothelium-dependent relaxation is impaired perhaps due to eNOS dysfunction, which might also contribute to maintain the blood pressure in Homo rats.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 1","pages":"Pages 38-44"},"PeriodicalIF":3.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000458/pdfft?md5=540649ac368aa19ed70b6770807da17e&pid=1-s2.0-S1347861324000458-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542563","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}

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