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The impact of endogenous N/OFQ on DPN: Insights into lower limb blood flow regulation in rats.
IF 2.5 3区 医学
Neuropeptides Pub Date : 2024-12-05 DOI: 10.1016/j.npep.2024.102492
Yuan-Jing Qin, Po Zhang, Peng Zhang, Jing Li, Qixing Yang, Jun-Li Sun, Yu-Zhang Liang, Li-Li Wang, Lin-Zhong Zhang, Yi Han
{"title":"The impact of endogenous N/OFQ on DPN: Insights into lower limb blood flow regulation in rats.","authors":"Yuan-Jing Qin, Po Zhang, Peng Zhang, Jing Li, Qixing Yang, Jun-Li Sun, Yu-Zhang Liang, Li-Li Wang, Lin-Zhong Zhang, Yi Han","doi":"10.1016/j.npep.2024.102492","DOIUrl":"https://doi.org/10.1016/j.npep.2024.102492","url":null,"abstract":"<p><p>Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, often accompanied by impaired vascular endothelial function in the lower limbs. This dysfunction is characterized by a reduced vasodilatory response, leading to decreased blood flow in the lower limbs and ultimately contributing to the development of diabetic peripheral neuropathy. To delve deeper into this pathological process, the study employed bioinformatics to identify and analyze genes highly active in DPN. The investigation revealed that Membrane metallo-endopeptidase (MME) was effectively mitigated by its antagonist. Male Sprague-Dawley (SD) rats served as the model to systematically explore the intrinsic connection among the nociceptible/orphanin FQ-N/OFQ receptor (N/OFQ-NOP) system, femoral artery blood flow in the lower extremities, MME, and DPN. The rats were randomized into two groups: a control group and a DPN group induced by a single intraperitoneal injection of 55 mg/kg streptozotocin (STZ), with 6 rats in each group. The findings indicated that compared to the control group, the DPN group exhibited a significant reduction in femoral artery blood flow. This was accompanied by a notable increase in serum N/OFQ concentration, heightened expression of opioid-related nociceptive protein receptor 1 (OPRL1) and MME in femoral artery tissues of the lower limbs, and an elevated sciatic nerve stimulation threshold. These results suggest that the serum N/OFQ level in DPN rats is increased, which may promote the occurrence of peripheral neuropathy by up regulating MME and reducing peripheral flow distribution.</p>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"109 ","pages":"102492"},"PeriodicalIF":2.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792147","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
FMRFamide G protein-coupled receptors (GPCR) in the cuttlefish Sepiella japonica: Identification, characterization and expression profile.
IF 2.5 3区 医学
Neuropeptides Pub Date : 2024-11-23 DOI: 10.1016/j.npep.2024.102491
Jian-Jun Xie, Ying Li, Jun-Hong Wu, Pei-Xuan Fang, Shuang Li, Xu Zhou, Chang-Feng Chi
{"title":"FMRFamide G protein-coupled receptors (GPCR) in the cuttlefish Sepiella japonica: Identification, characterization and expression profile.","authors":"Jian-Jun Xie, Ying Li, Jun-Hong Wu, Pei-Xuan Fang, Shuang Li, Xu Zhou, Chang-Feng Chi","doi":"10.1016/j.npep.2024.102491","DOIUrl":"https://doi.org/10.1016/j.npep.2024.102491","url":null,"abstract":"<p><p>FMRFamide is a ubiquitous neuromodulator in the animal kingdom. Once FMRFamide or similar neuropeptides bind to their G protein-coupled receptors (GPCR), a series of signal transduction events are triggered, thereby mediating various physiological effects. FMRFamide had been reported to be involved in the regulation of sexual maturation in Sepiella japonica. In this research, the full-length cDNA of FMRFamide G protein-coupled receptor of S. japonica (SjFaGPCR) was cloned. The sequence is 1396 bp long and encodes a protein consisting of 418 amino acid residues, lacking a signal peptide at the N-terminal region. The 3D structure of SjFaGPCR was predicted using Todarodes pacificus rhodopsin as a template, and the result indicated the presence of seven transmembrane regions. Multiple sequence alignments and phylogenetic trees indicated that SjFaGPCR is conserved among invertebrates, and shares highly similar sequence characteristics with other cephalopods. In situ hybridization (ISH) results revealed that significant signals of SjFaGPCR were detected in the central medulla and the granular layer cells of the optic lobe, and were also observed in the supraesophageal and subesophageal masses of the brain. Meanwhile, quantitative real-time PCR (qRT-PCR) results showed that a higher expression level of SjFaGPCR mRNA was detected in the brain and optic lobe of female cuttlefish at stage III and stage VI, and also in the brain (stage V) and optic lobe (stages IV and V) of male cuttlefish than that in other tissues. The co-localization results demonstrated that fluorescence signals of SjFMRFamide and SjFaGPCR were overlapped in HEK293 cells, suggesting a possible interaction between the SjFMRFamide and SjFaGPCR. These findings provide molecular support for further exploring the roles of FMRFamide and FaGPCR in the reproductive regulation of S. japonica.</p>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"109 ","pages":"102491"},"PeriodicalIF":2.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770728","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
Protective effect of Apelin-13 on D-glutamic acid-induced excitotoxicity in SH-SY5Y cell line: An in-vitro study Apelin-13对D-谷氨酸诱导的SH-SY5Y细胞系兴奋毒性的保护作用:体外研究
IF 2.5 3区 医学
Neuropeptides Pub Date : 2024-11-12 DOI: 10.1016/j.npep.2024.102483
Kadriye Yağmur Oruç , Gökhan Ağtürk , Aykut Oruç , Karolin Yanar , Hakkı Oktay Seymen
{"title":"Protective effect of Apelin-13 on D-glutamic acid-induced excitotoxicity in SH-SY5Y cell line: An in-vitro study","authors":"Kadriye Yağmur Oruç ,&nbsp;Gökhan Ağtürk ,&nbsp;Aykut Oruç ,&nbsp;Karolin Yanar ,&nbsp;Hakkı Oktay Seymen","doi":"10.1016/j.npep.2024.102483","DOIUrl":"10.1016/j.npep.2024.102483","url":null,"abstract":"<div><div>Excitotoxicity, resulting from excessive accumulation of glutamate in the extracellular space, leads to neuronal cell death. This study investigates the protective effects of Apelin-13 on D-Glutamic acid-induced excitotoxicity in SH-SY5Y human neuroblastoma cells, an in-vitro model for neurodegenerative diseases. Unlike the commonly studied L-glutamic acid, this research focuses on D-Glutamic acid to understand its specific impacts. SH-SY5Y cells were treated with varying concentrations of D-Glutamic acid and Apelin-13, followed by analyses at 12 and 24 h to evaluate cell viability, oxidative stress markers, and inflammatory cytokine levels. Cell viability assays revealed significant cytotoxic effects of D-Glutamic acid at doses of 10 mM and 20 mM, reducing viability by over 50 %. However, Apelin-13 treatment mitigated these effects, especially at 2 μg/ml, enhancing cell viability and reducing inflammatory cytokine levels (IL-1β and TNF-α). Apelin-13 also increased anti-inflammatory cytokine levels (IL-10 and TGF-β1) and brain-derived neurotrophic factor (BDNF), indicating its neuroprotective role. Oxidative stress markers, including ROS, AGE, AOPP, DT, T-SH, were significantly elevated by D-Glutamic acid but effectively reduced by Apelin-13. The neuroprotective mechanisms of Apelin-13 involve modulation of cAMP/PKA and MAPK signaling pathways, enhancing BDNF synthesis and suppressing oxidative stress and inflammatory responses. This study is the first to demonstrate the effects of D-Glutamic acid on SH-SY5Y cells. It highlights Apelin-13's potential as a therapeutic agent against excitotoxicity-induced neuronal damage, emphasizing its ability to modulate key molecular pathways involved in inflammation and oxidative stress. Further in-vivo studies are warranted to explore the long-term neuroprotective effects of Apelin-13 in treating neurodegenerative diseases.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"109 ","pages":"Article 102483"},"PeriodicalIF":2.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639305","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
Neuroanatomical mapping of spexin and nesfatin-1-expressing neurons in the human brainstem 人类脑干中表达 spexin 和 nesfatin-1 神经元的神经解剖图。
IF 2.5 3区 医学
Neuropeptides Pub Date : 2024-11-08 DOI: 10.1016/j.npep.2024.102484
Artur Pałasz , Klaudia Ozimirska , Aleksandra Suszka-Świtek , Katarzyna Bogus , Iwona Błaszczyk , Veerta Sharma , Marta Pukowiec , John J. Worthington , Izabela Młynarczuk-Biały , Anna Lipiec-Borowicz
{"title":"Neuroanatomical mapping of spexin and nesfatin-1-expressing neurons in the human brainstem","authors":"Artur Pałasz ,&nbsp;Klaudia Ozimirska ,&nbsp;Aleksandra Suszka-Świtek ,&nbsp;Katarzyna Bogus ,&nbsp;Iwona Błaszczyk ,&nbsp;Veerta Sharma ,&nbsp;Marta Pukowiec ,&nbsp;John J. Worthington ,&nbsp;Izabela Młynarczuk-Biały ,&nbsp;Anna Lipiec-Borowicz","doi":"10.1016/j.npep.2024.102484","DOIUrl":"10.1016/j.npep.2024.102484","url":null,"abstract":"<div><div>Neuropeptides are involved in numerous brain activities being able to control a wide spectrum of physiological functions. In recent years, a number of novel pleiotropic regulatory peptides have been discovered in animal brain structures. The purpose of this descriptive neurochemical investigation was to detect the possible expression of the novel multifunctional neuropeptides spexin (SPX) and nesfatin-1 within the human brainstem. Using immunohistochemical and fluorescence techniques, neuroanatomical analysis of the SPX and nesfatin-1 expression and distribution was performed in selected sections of the human midbrain and medulla oblongata. The presence of SPX-positive neurons in the human brainstem was revealed for the first time and previous reports on the expression of nesfatin-1 were additionally confirmed. The research results suggest that SPX and nesfatin-1 are new regulatory neuropeptides of the human brainstem potentially involved in the regulation of key autonomic activities of this brain region.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"109 ","pages":"Article 102484"},"PeriodicalIF":2.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624999","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
Neuropeptide FF prevented histamine- or chloroquine-induced acute itch behavior through non-NPFF receptors mechanism in male mice 神经肽 FF 通过非 NPFF 受体机制防止雄性小鼠出现组胺或氯喹诱发的急性瘙痒行为
IF 2.5 3区 医学
Neuropeptides Pub Date : 2024-11-04 DOI: 10.1016/j.npep.2024.102481
Honghai Tang , Ting Zhang , Jiamin Feng , Mengna Zhang , Biao Xu , Qinqin Zhang , Ning Li , Nan Zhang , Quan Fang
{"title":"Neuropeptide FF prevented histamine- or chloroquine-induced acute itch behavior through non-NPFF receptors mechanism in male mice","authors":"Honghai Tang ,&nbsp;Ting Zhang ,&nbsp;Jiamin Feng ,&nbsp;Mengna Zhang ,&nbsp;Biao Xu ,&nbsp;Qinqin Zhang ,&nbsp;Ning Li ,&nbsp;Nan Zhang ,&nbsp;Quan Fang","doi":"10.1016/j.npep.2024.102481","DOIUrl":"10.1016/j.npep.2024.102481","url":null,"abstract":"<div><div>The neuropeptide FF (NPFF) system regulates various physiological and pharmacological functions, particularly pain modulation. However, the modulatory effect of NPFF system on itch remains unclear. To investigate the modulatory effect and functional mechanism induced by NPFF system on acute itch, we examined the effects of supraspinal administration of NPFF and related peptides on acute itch induced by intradermal (i.d.) injection of histamine or chloroquine in male mice. Our results indicated that intracerebroventricular (i.c.v.) administration of NPFF dose-dependently prevented histamine- or chloroquine-induced acute itch behaviors. In addition, the modulatory effect of NPFF was not affected by the selective NPFF receptor antagonist RF9. Furthermore, we investigated the effects of NPVF and dNPA, the selective agonists of NPFF<sub>1</sub> and NPFF<sub>2</sub> receptors respectively, on the acute itch. The results demonstrated that both NPFF agonists effectively prevented acute itch induced by histamine or chloroquine in a manner similar to NPFF, and their effects were also not modified by RF9. To further investigate the possible mechanism of the NPFF receptors agonists, the NPFF-derived analogues [Phg<sup>8</sup>]-NPFF and NPFF(1–7)-NH<sub>2</sub> that could not activate NPFF receptors in cAMP assays were subsequently tested in the acute itch model. Interestingly, [Phg<sup>8</sup>]-NPFF, but not NPFF(1–7)-NH<sub>2</sub>, prevented acute itch behavior after i.c.v. administration. In conclusion, our findings reveal that NPFF and related peptides prevent histamine- and chloroquine-induced acute itch through a NPFF receptor-independent mechanism. And it was revealed that the C-terminal phenyl structure of NPFF may play a crucial role in these modulatory effects on acute itch.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"108 ","pages":"Article 102481"},"PeriodicalIF":2.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587200","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
Neuropeptides or their receptors in pathogenesis of lung diseases and therapeutic potentials 肺部疾病发病机制中的神经肽或其受体及其治疗潜力。
IF 2.5 3区 医学
Neuropeptides Pub Date : 2024-11-02 DOI: 10.1016/j.npep.2024.102482
Changgen Li , Na Zang , Enmei Liu
{"title":"Neuropeptides or their receptors in pathogenesis of lung diseases and therapeutic potentials","authors":"Changgen Li ,&nbsp;Na Zang ,&nbsp;Enmei Liu","doi":"10.1016/j.npep.2024.102482","DOIUrl":"10.1016/j.npep.2024.102482","url":null,"abstract":"<div><div>There are complex interactions between the immune system and the nervous system in the lung. The nervous system perceives environmental stimuli and transmits these signals to immune cells via neurotransmitters, which is essential for effective immunity and environmental balance. Neuropeptides are important neurotransmitters in the lung, where they regulate immune responses through direct and indirect mechanisms, affecting the occurrence and development of lung diseases. In this review, we emphasize the role of neuropeptides in the pathogeneis of lung diseases and their potential therapeutic value for lung diseases.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"108 ","pages":"Article 102482"},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624996","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
Neuritogenesis and protective effects activated by Angiotensin 1–7 in astrocytes-neuron interaction 血管紧张素 1-7 在星形胶质细胞与神经元相互作用中激活的神经细胞生成和保护作用
IF 2.5 3区 医学
Neuropeptides Pub Date : 2024-10-28 DOI: 10.1016/j.npep.2024.102480
Gabriel Alberto de Carvalho Barbosa , Marina Prado Rubinho , Milton Kennedy Aquino-Júnior , Jéssica Rodrigues Pedro , Lívia Fligioli Donato , Leonardo Trisciuzzi , Alessandra Oliveira Silva , Silvia Graciela Ruginsk , Carla Speroni Ceron , Nathalia Peixoto , Marcos Vinícios Salles Dias , Marília Gabriella Alves Goulart Pereira
{"title":"Neuritogenesis and protective effects activated by Angiotensin 1–7 in astrocytes-neuron interaction","authors":"Gabriel Alberto de Carvalho Barbosa ,&nbsp;Marina Prado Rubinho ,&nbsp;Milton Kennedy Aquino-Júnior ,&nbsp;Jéssica Rodrigues Pedro ,&nbsp;Lívia Fligioli Donato ,&nbsp;Leonardo Trisciuzzi ,&nbsp;Alessandra Oliveira Silva ,&nbsp;Silvia Graciela Ruginsk ,&nbsp;Carla Speroni Ceron ,&nbsp;Nathalia Peixoto ,&nbsp;Marcos Vinícios Salles Dias ,&nbsp;Marília Gabriella Alves Goulart Pereira","doi":"10.1016/j.npep.2024.102480","DOIUrl":"10.1016/j.npep.2024.102480","url":null,"abstract":"<div><div>The renin angiotensin system (RAS) has been studied for its effects on various neurological disorders. The identification of functional receptors for Ang-(1–7) and Ang II peptides in astrocytes highlights the physiological modulation and the important role of these cells in the central nervous system. The present study aims to understand the role of RAS peptides, particularly Ang-(1–7) and Ang II, in the secretion of trophic factors by astrocytes and their effects on hippocampal neurons. We used primary cultures of astrocytes and neurons from the hippocampus of either sex neonate of Wistar strain rats. In the present study, we demonstrated that the treatment of astrocytes with Ang-(1–7) acts on the modulation of these cells, inducing reactive astrogliosis, identified through the increase in the expression of GFAP. Furthermore, we obtained a conditioned medium from astrocytes treated with Ang-(1–7), which in addition to promoting the secretion of neurotrophic factors essential for neuronal-glial interactions that are fundamental for neuritogenesis and neuronal survival, showed a neuroprotective effect against glutamatergic excitotoxicity. In turn, Ang II does not exhibit the same effects on astrocyte modulation, exacerbating deleterious effects on brain RAS. Neuron-astrocyte interactions have been shown to be an integral part of the central effects mediated by RAS, and this study has significantly contributed to the understanding of the biochemical mechanisms involved in the functioning of this system.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"108 ","pages":"Article 102480"},"PeriodicalIF":2.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578926","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
Neuropeptide Y Y2 receptors in acute and chronic pain and itch 神经肽 Y Y2 受体在急性和慢性疼痛和瘙痒中的作用。
IF 2.5 3区 医学
Neuropeptides Pub Date : 2024-10-18 DOI: 10.1016/j.npep.2024.102478
Paramita Basu , Bradley K. Taylor
{"title":"Neuropeptide Y Y2 receptors in acute and chronic pain and itch","authors":"Paramita Basu ,&nbsp;Bradley K. Taylor","doi":"10.1016/j.npep.2024.102478","DOIUrl":"10.1016/j.npep.2024.102478","url":null,"abstract":"<div><div>Pain and itch are regulated by a diverse array of neuropeptides and their receptors in superficial laminae of the spinal cord dorsal horn (DH). Neuropeptide Y (NPY) is normally expressed on DH neurons but not sensory neurons. By contrast, the Npy2r receptor (Y2) is expressed on the central and peripheral terminals of sensory neurons but not on DH neurons. Neurophysiological slice recordings indicate that Y2-selective agonists inhibits spinal neurotransmitter release from sensory neurons. However, behavioral pharmacology studies indicate that Y2 agonists exert minimal changes in nociception, even after injury. Additional discrepancies in the behavioral actions of the Y2-antagonist BIIE0246 – reports of either pronociception or antinociception – have now been resolved. In the normal state, spinally-directed (intrathecal) administration of BIIE0246 elicits ongoing nociception, hypersensitivity to sensory stimulation, and aversion. Conversely, in the setting of nerve injury and inflammation, intrathecal BIIE024 reduced not only mechanical and thermal hypersensitivity, but also a measure of the affective dimension of pain (conditioned place preference). When administered in chronic pain models of latent sensitization, BIIE0246 produced a profound reinstatement of pain-like behaviors. We propose that tissue or nerve injury induces a G protein switch in the action of NPY-Y2 signaling from antinociception in the naïve state to the inhibition of mechanical and heat hyperalgesia in the injured state, and then a switch back to antinociception to keep LS in a state of remission. This model clarifies the pharmacotherapeutic potential of Y2 research, pointing to the development of a new non-opioid pharmacotherapy for chronic pain using Y2 antagonists in patients who do not develop LS.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"108 ","pages":"Article 102478"},"PeriodicalIF":2.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504905","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
NK1 receptor blockade disrupts microtumor growth and aggregation in a three-dimensional murine breast cancer model 阻断 NK1 受体可破坏三维鼠乳腺癌模型中微肿瘤的生长和聚集
IF 2.5 3区 医学
Neuropeptides Pub Date : 2024-10-16 DOI: 10.1016/j.npep.2024.102479
Silvia Gutierrez, M. Danilo Boada
{"title":"NK1 receptor blockade disrupts microtumor growth and aggregation in a three-dimensional murine breast cancer model","authors":"Silvia Gutierrez,&nbsp;M. Danilo Boada","doi":"10.1016/j.npep.2024.102479","DOIUrl":"10.1016/j.npep.2024.102479","url":null,"abstract":"<div><div>Several data indicate that Substance P (SP) neurokinin type 1 receptor (NK1R) is at the center of the interaction between cancer cells and peripheral sensory neurons. Selecting the appropriate cancer cell line and its susceptibility to being modulated by NK1 antagonists are critical to studying this complex interaction. In the current study, we have focused on this selection by comparing several aspects of the triple-negative breast cancer (TNBC) cell line (MDA-MB-231<sup>LUC+</sup>) with a modified murine cell line (E0771<sup>LUC+</sup>), both expressing luciferase. This comparison was made using several methods, SP stimulation and 3D cell culture models, to better reproduce the heterogenous microenvironment of solid tumors observed in vivo. Furthermore, the susceptibility of the murine cell line (E0771<sup>LUC+</sup>) to NK1R antagonist (Aprepitant) was tested. Our results indicate that E0771<sup>LUC+</sup> recapitulates several essential aspects of the human cell line, rendering this murine line ideal to be used on immune-competent animals during in vivo studies. We have also found that both cell lines are susceptible to SP stimulation, and their proliferation is disrupted by NK1R antagonists (Aprepitant). In vivo studies are required to verify and refine these findings.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"109 ","pages":"Article 102479"},"PeriodicalIF":2.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698070","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
Enteroendocrine cell-derived peptide YY signalling is stimulated by pinolenic acid or Intralipid and involves coactivation of fatty acid receptors FFA1, FFA4 and GPR119 蒎烯酸或 Intralipid 可刺激肠内分泌细胞衍生的肽 YY 信号,并涉及脂肪酸受体 FFA1、FFA4 和 GPR119 的协同激活。
IF 2.5 3区 医学
Neuropeptides Pub Date : 2024-10-11 DOI: 10.1016/j.npep.2024.102477
Iain R. Tough, Runisha Moodaley, Helen M. Cox
{"title":"Enteroendocrine cell-derived peptide YY signalling is stimulated by pinolenic acid or Intralipid and involves coactivation of fatty acid receptors FFA1, FFA4 and GPR119","authors":"Iain R. Tough,&nbsp;Runisha Moodaley,&nbsp;Helen M. Cox","doi":"10.1016/j.npep.2024.102477","DOIUrl":"10.1016/j.npep.2024.102477","url":null,"abstract":"<div><div>Long chain fatty acids are sensed by enteroendocrine L cells that express free-fatty acid receptors, including FFA1, FFA4 and the acylethanolamine receptor GPR119. Here we investigated the acute effects of single or multiple agonism at these G protein-coupled receptors in intestinal mucosae where L cell-derived peptide YY (PYY) is anti-secretory and acts via epithelial Y<sub>1</sub> receptors. Mouse ileal or colonic mucosae were mounted in Ussing chambers, voltage-clamped and the resultant short-circuit current (I<sub>sc</sub>) recorded continuously. The agonists used were; FFA1, TAK-875 or AM-1638; for FFA4, Merck A; or for GPR119, AR231453, PSN632408 or AR440006. Their responses were compared with those of pinolenic acid (PA, a presumed dual FFA1/FFA4 agonist) and the lipid emulsion, Intralipid. The FFA1 agonist AM-1638 (EC<sub>50</sub> = 38.2 nM) was more potent than TAK-875 (EC<sub>50</sub> = 203.1 nM) but exhibited similar efficacy. GPR119 agonism (AR231453) pretreatment enhanced subsequent FFA1 (AM-1638 or TAK-875) and FFA4 (Merck A) signalling. PA (EC<sub>50</sub> = 298.2 nM) co-activated epithelial FFA1 and FFA4 and involved endogenous PYY Y<sub>1</sub>/Y<sub>2</sub>-receptor mechanisms but desensitisation was observed between PA and high GPR119 agonist concentrations. Apical Intralipid co-activated FFA1, FFA4 and GPR119 with a residual component not being attributable to PYY, or this trio of fatty acid receptors.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"108 ","pages":"Article 102477"},"PeriodicalIF":2.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471043","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
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