Biological & pharmaceutical bulletin最新文献_第9页

RasGRP2 Attenuates TAGE Modification of eNOS in Vascular Endothelial Cells. RasGRP2减弱血管内皮细胞中eNOS的age修饰。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00730

Shouhei Miyazaki, Jun-Ichi Takino, Kentaro Nagamine, Masayoshi Takeuchi, Takamitsu Hori

{"title":"RasGRP2 Attenuates TAGE Modification of eNOS in Vascular Endothelial Cells.","authors":"Shouhei Miyazaki, Jun-Ichi Takino, Kentaro Nagamine, Masayoshi Takeuchi, Takamitsu Hori","doi":"10.1248/bpb.b24-00730","DOIUrl":"10.1248/bpb.b24-00730","url":null,"abstract":"Toxic advanced glycation end-products (TAGEs) are glyceraldehyde (GA)-derived AGEs with strong cytotoxic effects. TAGEs are also involved in lifestyle-related diseases. Notably, modification of TAGEs by GA causes protein dysfunction. As endothelial nitric oxide synthase (eNOS) is constitutively expressed in vascular endothelial cells and is a source of nitric oxide (NO), we focused on it as a TAGE modification-targeting protein. Our laboratory has reported that Ras guanyl nucleotide-releasing protein 2 (RasGRP2) activates Rap1 and R-Ras, among other small GTPases, and suppresses apoptosis and TAGE-induced vascular hyperpermeability in vascular endothelial cells. Therefore, in this study, we investigated the effects of RasGRP2 on cell death, TAGE formation, and TAGE modification of eNOS in vascular endothelial cells following GA treatment using RasGRP2-overexpressing (R) cells and mock (M) immortalized human umbilical vein endothelial cells. GA treatment decreases the viability of both cell types in a concentration-dependent manner. In M cells, GA treatment increased the formation of TAGEs and TAGE modification of eNOS in a concentration-dependent manner, but this increase was suppressed in R cells. Additionally, co-treatment with aminoguanidine, an inhibitor of AGEs formation, suppressed cell death and TAGE modification of eNOS induced by GA. These results indicate that GA induces cell death, the formation of TAGEs, and TAGE modification of eNOS in vascular endothelial cells. Additionally, RasGRP2 is a protective factor that suppresses TAGE formation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"262-266"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

5-Hydroxytryptamine Limits Pulmonary Arterial Hypertension Progression by Regulating Th17/Treg Balance. 5-羟色胺通过调节Th17/Treg平衡限制肺动脉高压进展。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00831

Junli Han, Lianghe Wang, Li Wang, Hua Lei

{"title":"5-Hydroxytryptamine Limits Pulmonary Arterial Hypertension Progression by Regulating Th17/Treg Balance.","authors":"Junli Han, Lianghe Wang, Li Wang, Hua Lei","doi":"10.1248/bpb.b24-00831","DOIUrl":"https://doi.org/10.1248/bpb.b24-00831","url":null,"abstract":"Pulmonary arterial hypertension (PAH) is a progressive disorder that lacks a validated and effective therapy. Thus, further investigation of the pathogenesis of PAH will help explore novel treatments. The increase in T helper 17 (Th17) cell-mediated pro-inflammatory response and reduction of regulatory T (Treg) cell-mediated anti-inflammatory effect exacerbates PAH progression. Increasing evidence indicates that 5-hydroxytryptamine (5-HT) is closely related to Th17 and Treg polarization. Here, a decrease of 5-HT was found in hypoxia-induced CD4 + T cells. Hypoxia also resulted in a reduction in Treg cells and an increase in Th17 cells, but the addition of 5-HT rescued Th17/Treg balance, confirming that hypoxia destroyed Th17/Treg balance by inducing a 5-HT decrease. Furthermore, we found that 5-HT-restored Th17/Treg balance mitigated primary pulmonary artery smooth muscle cell (PASMC) proliferation, migration, and contraction, which are important factors in vascular remodeling in PAH. In summary, our findings demonstrate that hypoxia-induced 5-HT decline interferes with the balance of Th17/Treg, which affects the biofunction of PASMCs, thus accelerating PAH development. 5-HT-mediated Th17/Treg balance is expected to act as a novel immunotherapy for PAH treatment.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"555-562"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Usefulness of an Intermittently Scanned Continuous Glucose Monitoring System for Risk Management of Individuals without Diabetes in Japan. 间歇性扫描连续血糖监测系统在日本非糖尿病患者风险管理中的应用

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00340

Aya Torii-Goto, Seiji Fukaya, Katsuo Amioka, Rei Shibata, Masae Yoshikawa

{"title":"Usefulness of an Intermittently Scanned Continuous Glucose Monitoring System for Risk Management of Individuals without Diabetes in Japan.","authors":"Aya Torii-Goto, Seiji Fukaya, Katsuo Amioka, Rei Shibata, Masae Yoshikawa","doi":"10.1248/bpb.b24-00340","DOIUrl":"10.1248/bpb.b24-00340","url":null,"abstract":"We examined whether the glucose levels and awareness of individuals without diabetes changed after using a sensor-based intermittently scanned continuous glucose monitoring (isCGM) system in their daily lives. Japanese individuals without a diabetes diagnosis wore the isCGM system while maintaining a normal lifestyle during the baseline period. A certified diabetes educator coached them on how to improve their lifestyle based on information from sensor data, food journals, and body composition. The participants subsequently consumed a specific diet, exercised for 2 months, and wore a new sensor after the intervention period. A total of 36 Japanese participants were eligible for analysis in this study. The time above range and the area under the curve did not change between before and after the intervention in overall participants. The visual analogue scale scores significantly increased from before to after the intervention in the overall participants. Stratified analysis was performed by dividing the participants into 18 control participants (glycated hemoglobin level <5.7%) and 18 participants with prediabetes (glycated hemoglobin level 5.7-6.4%). The time in range and the area under the curve significantly increased and decreased after the intervention in participants with prediabetes but not in control participants. The visual analogue scale scores significantly increased from before to after the intervention in both control and prediabetes groups individually. Lifestyle modification, along with the use of an isCGM system, is highly effective at preventing type 2 diabetes mellitus, potentially reducing the individual and public health burdens of diabetes, particularly for individuals with prediabetes.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"234-240"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

α₁-Adrenoceptor Blockade by Class I Antiarrhythmic Drugs in Guinea Pig Thoracic Aorta as Revealed by Mechanical and Fluorescence Displacement Analysis. 机械和荧光位移分析揭示ⅰ类抗心律失常药物对豚鼠胸主动脉α1-肾上腺素能受体的阻断作用。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00797

Iyuki Namekata, Maika Seki, Hiro Igarashi, Kohei Tsukada, Ayaka Kawazoe, Kuniaki Shirai, Marina Miyahara, Shogo Hamaguchi, Hikaru Tanaka

{"title":"α1-Adrenoceptor Blockade by Class I Antiarrhythmic Drugs in Guinea Pig Thoracic Aorta as Revealed by Mechanical and Fluorescence Displacement Analysis.","authors":"Iyuki Namekata, Maika Seki, Hiro Igarashi, Kohei Tsukada, Ayaka Kawazoe, Kuniaki Shirai, Marina Miyahara, Shogo Hamaguchi, Hikaru Tanaka","doi":"10.1248/bpb.b24-00797","DOIUrl":"10.1248/bpb.b24-00797","url":null,"abstract":"The effects of thirteen Vaughn Williams class I antiarrhythmic drugs on the α1-adrenergic receptor-mediated contraction were examined in thoracic aorta tissue preparations isolated from the guinea pig. Cibenzoline, quinidine, aprindine, and ranolazine, as well as prazosin, inhibited the phenylephrine-induced contraction with pA2 values of 5.64, 5.59, 5.61, 5.08, and 8.50, respectively, but not prostaglandin F2α-induced. These drugs reduced the staining of the smooth muscle layer by fluorescent prazosin. Propafenone inhibited the phenylephrine-induced contraction with an apparent pA2 value of 5.31 and reduced the staining by fluorescent prazosin, but also inhibited the prostaglandin F2α-induced contraction. Other class I antiarrhythmic drugs, disopyramide, pirmenol, procainamide, lidocaine, mexiletine, flecainide, pilsicainide, and GS-458967, affected neither the contraction by phenylephrine nor the fluorescent staining by prazosin. These results indicate that among the class I antiarrhythmic drugs, cibenzoline, aprindine, and propafenone, as well as quinidine and ranolazine, have α1-adrenoceptor-blocking activity at therapeutically relevant concentrations.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"144-150"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 3D Cell-Culture System That Uses Nano-Fibrillated Bacterial Cellulose to Prepare a Spherical Formulation of Culture Cells. 使用纳米纤维化细菌纤维素制备球形培养细胞的3D细胞培养系统。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00804

Shunsuke Akagi, Hidenori Ando, Cristina Nana Amorim Matsuo, Kenji Tajima, Haruka Takata, Tokuo Matsushima, Takatomo Kusano, Tatsuhiro Ishida

{"title":"A 3D Cell-Culture System That Uses Nano-Fibrillated Bacterial Cellulose to Prepare a Spherical Formulation of Culture Cells.","authors":"Shunsuke Akagi, Hidenori Ando, Cristina Nana Amorim Matsuo, Kenji Tajima, Haruka Takata, Tokuo Matsushima, Takatomo Kusano, Tatsuhiro Ishida","doi":"10.1248/bpb.b24-00804","DOIUrl":"10.1248/bpb.b24-00804","url":null,"abstract":"A 3-dimensional (3D) cell culture is now being actively pursued to accomplish the in vivo-like cellular morphology and biological functions in cell culture. We recently obtained nano-fibrillated bacterial cellulose (NFBC). In this study, we developed a novel NFBC-based 3D cell-culture system, the OnGel method, and the Suspension method. HepG2 human liver cancer cells were cultured via these methods and formed spherical formulations in the optimized condition, 1.0% (w/v) of NFBC in the OnGel method, and 0.06-0.10% (w/v) of NFBC in the Suspension method. Non-cancerous cells such as human-induced pluripotent stem (iPS) cells and human mesenchymal stem cells (MSCs) also formed spherical formulations. It is noteworthy that both the size and cell viability of spheroids prepared via these methods were comparable to those cultured using commercially available 3D cell-culture systems. Both OnGel and Suspension methods are less complicated than the existing 3D cell-culture systems, which is an invaluable advantage for the preparation of cancer spheroids. The NFBC-based 3D cell-culture systems introduced here show great promise as a tool to prepare cultures for cell-derived spheroids for the progress of both in vitro and in vivo studies of the biological functioning of cells.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"23-32"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Functional Analysis of Modified Caco-2 Cells Carrying CES2A1 as a Model for Intestinal Absorption of Prodrugs. 携带CES2A1修饰Caco-2细胞作为前药肠道吸收模型的功能分析。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00645

Teruko Imai, Masanari Isasaka, Yusuke Oyama, Yusuke Takagi, Kayoko Ohura, Shunsuke Kotani, Yuichiro Nakada

{"title":"Functional Analysis of Modified Caco-2 Cells Carrying CES2A1 as a Model for Intestinal Absorption of Prodrugs.","authors":"Teruko Imai, Masanari Isasaka, Yusuke Oyama, Yusuke Takagi, Kayoko Ohura, Shunsuke Kotani, Yuichiro Nakada","doi":"10.1248/bpb.b24-00645","DOIUrl":"10.1248/bpb.b24-00645","url":null,"abstract":"Carboxylesterase (CES) plays an important role in the metabolism of ester-containing drugs such as prodrugs and is highly expressed in the human intestine and liver. The ideal prodrug is barely hydrolyzed by human intestinal CES (CES2A1) but is extensively converted to an active drug by human hepatic CES (CES1A). It is, therefore, important to evaluate CES2A1-mediated hydrolysis during intestinal absorption. Unfortunately, Caco-2 cells, the most common enterocyte model for drug permeability, are not suitable for permeability studies of prodrugs due to their high and extremely low expression of CES1A and CES2A1, respectively. Previously, we have prepared CES2/Caco-2CES1KD cells with reduced human CES1A and highly expressed CES2A1. In the present study, the metabolic and transport properties of CES2/Caco-2CES1KD cells were characterized. The expression of transporters and metabolizing enzymes other than CESs was similar in CES2/Caco-2CES1KD and Caco-2 cells. However, the expression of CES2A1 in CES2/Caco-2CES1KD was about 7-10 fold higher than that of CES1A in Caco-2 cells and comparable to levels found in the human intestine. Hydrolysis during transport across cell monolayers was analyzed using ethyl and butyl esters of p-aminobenzoic acid (PABA). Ethyl PABA, a better substrate for CES1A than CES2A1, was similarly hydrolyzed in Caco-2 and CES2/Caco-2CES1KD cell monolayers due to the high expression of CES2A1 in CES2/Caco-2CES1KD cells. Butyl PABA, a good substrate for CES2A1, was substantially hydrolyzed in CES2/Caco-2CES1KD cell monolayers, in contrast to negligible hydrolysis in Caco-2 cell monolayers. N-Acetylation of PABA derived from PABA esters showed similar activity in Caco-2 and CES2/Caco-2CES1KD cell monolayers.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"162-171"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Effect of (p)ppGpp on the Expression of the Vibrioferrin-Mediated Iron Acquisition System in Vibrio parahaemolyticus. (p)ppGpp对副溶血性弧菌铁蛋白介导的铁获取系统表达的影响。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00624

Tomotaka Tanabe, Katsushiro Miyamoto, Kenjiro Nagaoka, Hiroshi Tsujibo, Tatsuya Funahashi

{"title":"Effect of (p)ppGpp on the Expression of the Vibrioferrin-Mediated Iron Acquisition System in Vibrio parahaemolyticus.","authors":"Tomotaka Tanabe, Katsushiro Miyamoto, Kenjiro Nagaoka, Hiroshi Tsujibo, Tatsuya Funahashi","doi":"10.1248/bpb.b24-00624","DOIUrl":"10.1248/bpb.b24-00624","url":null,"abstract":"Bacteria have a stringent response system mediated by guanosine pentaphosphate and tetraphosphate ((p)ppGpp), which suppresses the expression of genes involved in cell growth and promotes the expression of genes involved in nutrient uptake and metabolism under nutrient-limited stress. In environments with limited availability of iron, an essential trace element, bacteria generally produce and secrete siderophores to efficiently utilize water-insoluble ferric iron (Fe3+) in the environment. In Vibrio parahaemolyticus, Fur (iron-responsive repressor) and RyhB (Fur-regulated small RNA) regulate the expression of genes involved in the utilization of vibrioferrin (VF), a siderophore produced by this bacterium. In this study, we examined whether (p)ppGpp is also involved in regulating the expression of genes related to the VF utilization system. Results of the chrome azurol S plate assay revealed that the strain in which 3 (p)ppGpp synthetases were deleted (∆relA∆spoT∆relV) produced less VF than the parental strain. Growth test results showed that the growth rate of ∆relA∆spoT∆relV in an iron-limited medium was suppressed compared with that of the parental strain but was restored with the addition of VF. Furthermore, RT-quantitative (q)PCR results showed that the expression levels of pvsA (VF biosynthesis gene) and pvuA2 (ferric VF receptor gene) in ∆relA∆spoT∆relV under iron limitation were significantly reduced compared with those in the parental strain. Western blot results demonstrated that the expression level of PvuA2 in ∆relA∆spoT∆relV was lower than that in the parental strain. These results suggest that (p)ppGpp promotes the expression of genes related to VF biosynthesis and the ferric VF uptake system under iron limitation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"188-194"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Point Mutation Analysis of the Drug Efflux Pump MexB in Clinical Isolates of Pseudomonas aeruginosa. 铜绿假单胞菌药物外排泵MexB的点突变分析。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b23-00190

Seiji Yamasaki, Naoki Koga, Ryosuke Nakashima, Mitsuko Hayashi-Nishino, Kunihiko Nishino

{"title":"Point Mutation Analysis of the Drug Efflux Pump MexB in Clinical Isolates of Pseudomonas aeruginosa.","authors":"Seiji Yamasaki, Naoki Koga, Ryosuke Nakashima, Mitsuko Hayashi-Nishino, Kunihiko Nishino","doi":"10.1248/bpb.b23-00190","DOIUrl":"10.1248/bpb.b23-00190","url":null,"abstract":"The rapid emergence of drug-resistant microbes has recently become a major concern in the medical field. In Pseudomonas aeruginosa, one of the most important mechanisms underlying antibiotic resistance is MexAB-OprM system, increases in this efflux system result in greater resistance to a wide range of drugs, and genetic mutations have been identified as a contributing factor. Thus, this study characterized point mutations in the mexB gene that are common to 39 clinical P. aeruginosa isolates obtained from The Pseudomonas Genome Database. Basic Local Alignment Search Tool (BLAST) was used to compare the mexB gene sequences of those 39 strains with PAO1. The majority of these point mutations were silent mutations without amino acid mutations. Mutations 2730, 495, and 2280, which were abundant in the strains examined, were characterized by greater codon usage after the mutation. A positive correlation has been reported between tRNA levels and codon usage in Escherichia coli, and the same relationship may be present in P. aeruginosa. In this study, the silent mutations observed in many strains mainly involved the substitution of C or G, which resulted in a higher codon usage and stronger binding power after than before the mutation. This change is considered advantageous for survival in the human body by increasing the translation efficiency of the MexB protein. Thus, combining the silent mutation identified in this study with information on the expression level of mexB is expected to be used as an indicator to identify multidrug-resistant P. aeruginosa.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"230-233"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Evidence Showing Bombesin-Like Peptides Contract Guinea Pig Vas Deferens Smooth Muscle. 证据显示炸弹素样肽收缩豚鼠输精管平滑肌。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00721

Ge Liu, Hiryu Fujita, Hayato Agui, Ayu Kato, Miwa Enomoto, Futaba Makino, Nana Yamada, Kento Yoshioka, Keisuke Obara, Yoshio Tanaka

{"title":"Evidence Showing Bombesin-Like Peptides Contract Guinea Pig Vas Deferens Smooth Muscle.","authors":"Ge Liu, Hiryu Fujita, Hayato Agui, Ayu Kato, Miwa Enomoto, Futaba Makino, Nana Yamada, Kento Yoshioka, Keisuke Obara, Yoshio Tanaka","doi":"10.1248/bpb.b24-00721","DOIUrl":"10.1248/bpb.b24-00721","url":null,"abstract":"In this study, we investigated (1) the functional role of large-conductance Ca2+-activated K+ (BKCa) channels in the regulation of guinea pig vas deferens smooth muscle (VDSM) contractions and (2) the potential contractile effects of 33 physiologically active substances and related chemicals that have not been previously reported to contract VDSM. Iberiotoxin (an inhibitor of BKCa channels, 10-7 M) was the most potent enhancer of both noradrenaline (10-5 M)- and ATP (10-6 M)-induced contractions among the 6 types of K+ channel inhibitors. In addition, BKCa channel mRNA expression was the highest among the 32 types of K+ channel mRNAs. Iberiotoxin also enhanced the contractions induced by acetylcholine (10-6 M), histamine (5 × 10-5 M), bradykinin (10-6 M), neurokinin A (10-6 M), neurokinin B (10-6 M), and substance P (10-6 M). In the 33 tested physiologically active substances and related chemicals (15 peptides, 5 amino acids and their derivatives, 11 prostanoid- and isoprostane-related drugs, 1 endocannabinoid, and 1 phospholipid), we found that 3 bombesin-like peptides, neuromedin B (NMB) (10-6 M), gastrin-releasing peptide (GRP, 10-8 M), and NMC (10-6 M), contracted VDSM in the absence of iberiotoxin, and these contractions were strongly enhanced in the presence of iberiotoxin. Among the 3 bombesin receptor subtypes, the mRNA expression level of Grpr (BB2 receptor) was the highest. These findings suggest that (1) BKCa channels are the most powerful negative regulator of VDSM contractility and (2) NMB, GRP, and NMC are physiologically active substances that contract VDSM.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"298-307"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Ameliorative Effect of Ninjinyoeito on Reductions in Self-grooming in Lipopolysaccharide-Injected Mice: Involvement of Alpha7 Nicotinic Acetylcholine Receptor. 健宁对脂多糖注射小鼠自我修饰减少的改善作用：α 7烟碱乙酰胆碱受体的参与。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00510

Takuya Watanabe, Marika Hirata, Shutaro Nakashima, Chise Taniguchi, Akinobu Hatae, Kaori Kubota, Shutaro Katsurabayashi, Katsunori Iwasaki

{"title":"Ameliorative Effect of Ninjinyoeito on Reductions in Self-grooming in Lipopolysaccharide-Injected Mice: Involvement of Alpha7 Nicotinic Acetylcholine Receptor.","authors":"Takuya Watanabe, Marika Hirata, Shutaro Nakashima, Chise Taniguchi, Akinobu Hatae, Kaori Kubota, Shutaro Katsurabayashi, Katsunori Iwasaki","doi":"10.1248/bpb.b24-00510","DOIUrl":"https://doi.org/10.1248/bpb.b24-00510","url":null,"abstract":"Ninjinyoeito (NYT) is a Japanese herbal medicine that is prescribed for individuals with depleted mental and physical energy. In this study, we examined the mechanism underlying the effect of NYT on depleted mental and physical energy in mice following a simulated infection. Injection of lipopolysaccharide (LPS), a bacterial endotoxin, decreased the motivational behaviors and body weight of the mice. One of the decreased motivational behaviors, reduced self-grooming, was ameliorated by the continuous administration of NYT. But NYT did not ameliorate reductions in the other motivational behaviors of nest building and food consumption. Furthermore, a single administration of NYT also ameliorated the reduction in self-grooming. PNU282987, an agonist of the alpha7 nicotinic acetylcholine receptor (α7 nAChR), also ameliorated the reduction in self-grooming. Blocking α7 nAChR by methyllycaconitine, an α7 nAChR antagonist, canceled any improvements in self-grooming induced by NYT. Together, these results suggest that NYT ameliorates diminished motivation for self-care via the activation of α7 nAChR.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"728-732"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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