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Opioid growth factor receptor: Anatomical distribution and receptor colocalization in neurons of the adult mouse brain 阿片生长因子受体:成年小鼠脑神经元的解剖分布和受体共定位
IF 2.9 3区 医学
Neuropeptides Pub Date : 2023-06-01 DOI: 10.1016/j.npep.2023.102325
Zainab Y. Kareem, Patricia J. McLaughlin, Rashmi Kumari
{"title":"Opioid growth factor receptor: Anatomical distribution and receptor colocalization in neurons of the adult mouse brain","authors":"Zainab Y. Kareem,&nbsp;Patricia J. McLaughlin,&nbsp;Rashmi Kumari","doi":"10.1016/j.npep.2023.102325","DOIUrl":"10.1016/j.npep.2023.102325","url":null,"abstract":"<div><p><span><span>The opioid growth factor (OGF) is an endogenous peptide that binds to the nuclear-associated receptor (OGFr), and plays a significant role in the proliferation of developing, renewing, and healing tissues. The receptor is widely expressed in a variety of organs, however its distribution in the brain remains unknown. In this study, we investigated the distribution of </span>OGFr in different brain regions of male heterozygous (-/+ Lepr </span><sup>db</sup><span><span><span><span><span>/J), non -diabetic mice and determined the localization of the receptor in three major brain cell types, astrocytes, microglia, and neurons. </span>Immunofluorescence imaging revealed that the highest number of OGFr was in hippocampal CA3 subregion followed by primary </span>motor cortex<span><span>, hippocampal CA2, thalamus, caudate and </span>hypothalamus in a descending order. Double </span></span>immunostaining<span><span> revealed receptor colocalization with neurons and little or no colocalization in microglia and astrocytes. The highest percentage of OGFr positive neurons was identified in the CA3. Hippocampal CA3 neurons play an important role in memory processing, learning and behavior, and motor cortex neurons are important for muscle movement. However, the significance of the OGFr receptor in these brain regions and its relevance in diseased conditions are not known. Our findings provide a basis for understanding the cellular target and interaction of the OGF- OGFr pathway in </span>neurodegenerative diseases<span><span> such as Alzheimer's, Parkinson's, and stroke where hippocampus and cortex have an important role. This foundational data may also be useful in </span>drug discovery to modulate OGFr by </span></span></span>opioid receptor<span> antagonist in various CNS diseases.</span></span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"99 ","pages":"Article 102325"},"PeriodicalIF":2.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9801415","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: 3
Sex-dimorphic hindbrain lactate regulation of ventromedial hypothalamic nucleus glucoregulatory neuron 5’-AMP-activated protein kinase activity and transmitter marker protein expression 下丘脑腹内侧核糖调节神经元5'-AMP活化蛋白激酶活性和递质标记蛋白表达的性别二型后脑乳酸调节
IF 2.9 3区 医学
Neuropeptides Pub Date : 2023-06-01 DOI: 10.1016/j.npep.2023.102324
Prabhat R. Napit , Md. Haider Ali , A.S.M. Hasan Mahmood, Mostafa M.H. Ibrahim, Karen P. Briski
{"title":"Sex-dimorphic hindbrain lactate regulation of ventromedial hypothalamic nucleus glucoregulatory neuron 5’-AMP-activated protein kinase activity and transmitter marker protein expression","authors":"Prabhat R. Napit ,&nbsp;Md. Haider Ali ,&nbsp;A.S.M. Hasan Mahmood,&nbsp;Mostafa M.H. Ibrahim,&nbsp;Karen P. Briski","doi":"10.1016/j.npep.2023.102324","DOIUrl":"10.1016/j.npep.2023.102324","url":null,"abstract":"<div><h3>Background</h3><p>The oxidizable glycolytic end-product L-lactate is a gauge of nerve cell metabolic fuel stability that metabolic-sensory hindbrain A2 noradrenergic neurons impart to the brain glucose-regulatory network. Current research investigated the premise that hindbrain lactate deficiency exerts sex-specific control of energy sensor and transmitter marker protein responses to hypoglycemia in ventromedial hypothalamic nucleus (VMN) glucose-regulatory nitrergic and γ-aminobutyric acid (GABA) neurons.</p></div><div><h3>Methods</h3><p><span><span>Nitric oxide synthase (nNOS)- or </span>glutamate decarboxylase</span><sub>65/67</sub><span><span> (GAD)-immunoreactive neurons were laser-catapult-microdissected from male and female rat VMN after subcutaneous insulin injection and caudal fourth ventricular L-lactate or vehicle infusion for Western blot </span>protein analysis.</span></p></div><div><h3>Results</h3><p><span><span>Hindbrain lactate repletion reversed hypoglycemia-associated augmentation (males) or inhibition (females) of nitrergic neuron </span>nNOS<span> expression, and prevented up-regulation of phosphorylated AMPK 5’-AMP-activated protein kinase (pAMPK) expression in those neurons. </span></span>Hypoglycemic<span><span> suppression of GABAergic neuron GAD protein was averted by exogenous lactate over the rostro-caudal length of the male VMN and in the middle region of the female VMN. Lactate normalized GABA neuron pAMPK profiles in hypoglycemic male (caudal VMN) and female (all VMN segments) rats. Hypoglycemic patterns of </span>norepinephrine (NE) signaling were lactate-dependent throughout the male VMN, but confined to the rostral and middle female VMN.</span></p></div><div><h3>Conclusions</h3><p><span>Results document, in each sex, regional VMN glucose-regulatory transmitter responses to hypoglycemia that are controlled by hindbrain lactate status. Hindbrain metabolic-sensory regulation of hypoglycemia-correlated nitric oxide or GABA release may entail AMPK-dependent mechanisms in specific VMN rostro-caudal segments in each sex. Additional effort is required to examine the role of hindbrain lactoprivic-sensitive VMN </span>neurotransmitters<span> in lactate-mediated attenuation of hypoglycemic hyperglucagonemia and hypercorticosteronemia in male and female rats.</span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"99 ","pages":"Article 102324"},"PeriodicalIF":2.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9449179","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: 1
Orexin receptor antagonists in the pathophysiology and treatment of sleep disorders and epilepsy Orexin受体拮抗剂在睡眠障碍和癫痫的病理生理学和治疗中的作用
IF 2.9 3区 医学
Neuropeptides Pub Date : 2023-06-01 DOI: 10.1016/j.npep.2023.102335
Mohammad Sheibani , Maryam Shayan , Mina Khalilzadeh , Mehdi Ghasemi , Ahmad Reza Dehpour
{"title":"Orexin receptor antagonists in the pathophysiology and treatment of sleep disorders and epilepsy","authors":"Mohammad Sheibani ,&nbsp;Maryam Shayan ,&nbsp;Mina Khalilzadeh ,&nbsp;Mehdi Ghasemi ,&nbsp;Ahmad Reza Dehpour","doi":"10.1016/j.npep.2023.102335","DOIUrl":"10.1016/j.npep.2023.102335","url":null,"abstract":"<div><p><span>The correlation between sleep and epilepsy has been argued over the past decades among scientists. Although the similarities and contrasts between sleep and epilepsy had been considered, their intertwined nature was not revealed until the nineteenth century. Sleep is recognized as a recurring state of mind and body through alternating brain electrical activities. It is documented that sleep disorders are associated with epilepsy. The origin, suppression, and spread of seizures are affected by sleep. As such, </span>in patients<span><span> with epilepsy, sleep disorders are a frequent comorbidity. Meanwhile, orexin<span>, a wake-promoting neuropeptide, provides a bidirectional effect on both sleep and epilepsy. Orexin and its cognate receptors, </span></span>orexin receptor<span> type 1 (OX1R) and type 2 (OX2R), orchestrate their effects by activating various downstream signaling pathways. Although orexin was considered a therapeutic target in insomnia shortly after its discovery, its potential usefulness for psychiatric disorders and epileptic seizures has been suggested in the pre-clinical studies. This review aimed to discuss whether the relationship between sleep, epilepsy, and orexin is clearly reciprocal.</span></span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"99 ","pages":"Article 102335"},"PeriodicalIF":2.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9805731","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: 6
Curcumin attenuates morphine dependence by modulating μ-opioid receptors and glial cell-activated neuroinflammation in rat 姜黄素通过调节μ-阿片受体和神经胶质细胞激活的神经炎症减轻吗啡依赖
IF 2.9 3区 医学
Neuropeptides Pub Date : 2023-04-01 DOI: 10.1016/j.npep.2022.102318
Mohammad Abbas Sheikholeslami, Siavash Parvardeh, Shiva Ghafghazi, Masoumeh Sabetkasaei
{"title":"Curcumin attenuates morphine dependence by modulating μ-opioid receptors and glial cell-activated neuroinflammation in rat","authors":"Mohammad Abbas Sheikholeslami,&nbsp;Siavash Parvardeh,&nbsp;Shiva Ghafghazi,&nbsp;Masoumeh Sabetkasaei","doi":"10.1016/j.npep.2022.102318","DOIUrl":"10.1016/j.npep.2022.102318","url":null,"abstract":"<div><p><span><span><span>In recent years, the association between neuroinflammation and </span>opioid dependence has attracted considerable attention. </span>Curcumin, a component of the </span><span><em>Curcuma</em><em> longa</em></span><span><span><span>, has been shown to act as a suppressor of glial cells and inflammatory cytokines. The main goal of this study was to explore the attenuating effects of curcumin on </span>morphine dependence<span><span> with a focus on neuroinflammation and μ-opioid receptors in the rat prefrontal cortex. To induce morphine dependence in male </span>Wistar rats<span>, morphine was administered i.p. once daily for 18 days in an escalating dose of 10, 20, and 40 mg/kg. Curcumin (2.5, 5, and 10 mg/kg, i.p.) was given from the days 10th to 18th. Immunofluorescence </span></span></span>staining<span><span><span> and ELISA methods were used to evaluate glial cells activity and inflammatory cytokines levels, respectively. </span>Western blotting was used to evaluate the expression of μ-opioid receptors. The administration of curcumin (2.5, 5, and 10 mg/kg) for 9 days significantly attenuated the symptoms of morphine withdrawal syndrome. The prefrontal cortex concentration of TNF-α and IL-6 was also reduced by curcumin (2.5, 5, and 10 mg/kg) significantly. Furthermore, curcumin decreased the number of </span>Iba1<span> and GFAP positive cells in morphine-dependent rats. Moreover, the expression of μ-opioid receptors was significantly reduced by curcumin (10 mg/kg). The results of this study demonstrate that curcumin attenuates morphine dependence in rats through an inhibitory effect on neuroinflammation and a decrease in the expression of μ-opioid receptors in the prefrontal cortex.</span></span></span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"98 ","pages":"Article 102318"},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9449073","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: 1
Investigating the potential of GalR2 as a drug target for neuropathic pain 研究GalR2作为神经性疼痛药物靶点的潜力
IF 2.9 3区 医学
Neuropeptides Pub Date : 2023-04-01 DOI: 10.1016/j.npep.2022.102311
Kirsty Rich , Samrina Rehman , Jeff Jerman , Graeme Wilkinson
{"title":"Investigating the potential of GalR2 as a drug target for neuropathic pain","authors":"Kirsty Rich ,&nbsp;Samrina Rehman ,&nbsp;Jeff Jerman ,&nbsp;Graeme Wilkinson","doi":"10.1016/j.npep.2022.102311","DOIUrl":"10.1016/j.npep.2022.102311","url":null,"abstract":"<div><p><span><span>Neuropathic pain is a chronic and debilitating condition characterised by episodes of </span>hyperalgesia and </span>allodynia<span>. It occurs following nerve damage from disease, inflammation or injury and currently impacts up to 17% of the UK population. Existing therapies lack efficacy and have deleterious side effects that can be severely limiting.</span></p><p><span>Galanin receptor 2 (GalR2) is a G-protein coupled receptor (GPCR) implicated in the control and processing of painful stimuli. Within the </span>nervous system<span><span> it is expressed in key tissues involved in these actions such as dorsal root<span> ganglia<span> (DRG) and the dorsal horn of the spinal cord. Stimulation of GalR2 is widely reported to have a role in the attenuation of inflammatory and neuropathic pain. Several studies have indicated GalR2 as a possible </span></span></span>drug target, highlighting the potential of specific GalR2 agonists to both provide efficacy and to address the side-effect profiles of current pain therapies in clinical use.</span></p><p>A strong biological target for drug discovery will be well validated with regards to its role in the relevant disease pathology. Ideally there will be good translational models, sensitive probes, selective and appropriate molecular tools, translational biomarkers, a clearly defined patient population and strong opportunities for commercialisation. Before GalR2 can be considered as a drug target suitable for investment, key questions need to be asked regarding its expression profile, receptor signalling and ligand interactions. This article aims to critically review the available literature and determine the current strength of hypothesis of GalR2 as a target for the treatment of neuropathic pain.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"98 ","pages":"Article 102311"},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9072926","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: 1
Altered neurotransmission in stress-induced depressive disorders: The underlying role of the amygdala in depression 应激性抑郁症的神经传递改变:杏仁核在抑郁症中的潜在作用
IF 2.9 3区 医学
Neuropeptides Pub Date : 2023-04-01 DOI: 10.1016/j.npep.2023.102322
Muhammad Asim , Huajie Wang , Abdul Waris
{"title":"Altered neurotransmission in stress-induced depressive disorders: The underlying role of the amygdala in depression","authors":"Muhammad Asim ,&nbsp;Huajie Wang ,&nbsp;Abdul Waris","doi":"10.1016/j.npep.2023.102322","DOIUrl":"10.1016/j.npep.2023.102322","url":null,"abstract":"<div><p><span>Depression is the second leading cause of disability in the world population, for which currently available pharmacological therapies either have poor efficacy or have some adverse effects<span><span>. Accumulating evidence from clinical and preclinical studies demonstrates that the </span>amygdala is critically implicated in depressive disorders, though the underlying pathogenesis mechanism needs further investigation. In this literature review, we overviewed depression and the key role of Gamma-aminobutyric acid (GABA) and </span></span>Glutamate<span> neurotransmission<span> in depression. Notably, we discussed a new cholecystokinin-dependent plastic changes mechanism under stress and a possible antidepressant response of cholecystokinin<span> B receptor (CCKBR) antagonist. Moreover, we discussed the fundamental role of the amygdala in depression, to discuss and understand the pathophysiology of depression and the inclusive role of the amygdala in this devastating disorder.</span></span></span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"98 ","pages":"Article 102322"},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9082566","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: 2
Interactions between the regulatory peptide 26RFa (QRFP) and insulin in the regulation of glucose homeostasis in two complementary models: The high fat 26RFa-deficient mice and the streptozotocin insulin-deficient mice 调节肽26RFa (QRFP)和胰岛素在两种互补模型中调节葡萄糖稳态的相互作用:高脂26RFa缺陷小鼠和链脲佐菌素胰岛素缺陷小鼠
IF 2.9 3区 医学
Neuropeptides Pub Date : 2023-04-01 DOI: 10.1016/j.npep.2023.102326
Marie-Anne Le Solliec , Arnaud Arabo , Saloua Takhlidjt , Julie Maucotel , Mélodie Devère , Hind Berrahmoune , Alexandre Bénani , Emmanuelle Nedelec , Benjamin Lefranc , Jérôme Leprince , Marie Picot , Nicolas Chartrel , Gaëtan Prévost
{"title":"Interactions between the regulatory peptide 26RFa (QRFP) and insulin in the regulation of glucose homeostasis in two complementary models: The high fat 26RFa-deficient mice and the streptozotocin insulin-deficient mice","authors":"Marie-Anne Le Solliec ,&nbsp;Arnaud Arabo ,&nbsp;Saloua Takhlidjt ,&nbsp;Julie Maucotel ,&nbsp;Mélodie Devère ,&nbsp;Hind Berrahmoune ,&nbsp;Alexandre Bénani ,&nbsp;Emmanuelle Nedelec ,&nbsp;Benjamin Lefranc ,&nbsp;Jérôme Leprince ,&nbsp;Marie Picot ,&nbsp;Nicolas Chartrel ,&nbsp;Gaëtan Prévost","doi":"10.1016/j.npep.2023.102326","DOIUrl":"10.1016/j.npep.2023.102326","url":null,"abstract":"<div><p><span>The regulatory peptide 26RFa (QRFP) is involved in the control of glucose homeostasis<span><span> at the periphery by acting as an incretin, and in the brain by mediating the central antihyperglycemic effect of insulin, indicating the occurrence of a close relationship between 26RFa and insulin in the regulation of </span>glucose metabolism<span>. Here, we investigated the physiological interactions between 26RFa and insulin in two complementary models i.e. a model of obese/hyperglycemic mice deficient for 26RFa and a model of diabetic mice deficient for insulin. For this, transgenic 26RFa-deficient mice were made obese and chronically hyperglycemic by a 3-month </span></span></span>high fat diet<span><span> (HFD) and second group of mice was made diabetic by destruction of the β cells of the pancreatic islets using a single injection of </span>streptozotocin<span>. Our data reveal that 26RFa deficiency does not impact significantly the “glycemic” phenotype of the HFD mice. The pancreatic islets, liver, white adipose tissue<span><span> masses are not altered by the lack of 26RFa production but the brown adipose tissue (BAT) weight is significantly increased in these animals. In diabetic insulin-deficient mice, the injection of 26RFa does not exhibit any beneficial effect on the impaired glucose homeostasis characterizing this model. Finally, we show that streptozotocin diabetic mice display lowered plasma 26RFa levels as compared to untreated mice, whereas the expression of the peptide in the </span>duodenum is not affected.</span></span></span></p><p>Taken together, the present results indicate that dysregulation of glucose homeostasis in obese/hyperglycemic mice is not aggravated by the absence of 26RFa that may be compensated by the increase of BAT mass. In diabetic insulin-deficient mice, the antihypergycemic effect of 26RFa is totally blunted probably as a result of the impaired insulin production characterizing this model, avoiding therefore the action of the peptide.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"98 ","pages":"Article 102326"},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9073938","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
Search for lipidized PrRP analogs with strong anorexigenic effect: In vitro and in vivo studies 寻找具有强烈厌食作用的脂质化PrRP类似物:体外和体内研究
IF 2.9 3区 医学
Neuropeptides Pub Date : 2023-04-01 DOI: 10.1016/j.npep.2022.102319
Veronika Strnadová , Alena Karnošová , Miroslava Blechová , Barbora Neprašová , Lucie Holá , Anna Němcová , Aneta Myšková , David Sýkora , Blanka Železná , Jaroslav Kuneš , Lenka Maletínská
{"title":"Search for lipidized PrRP analogs with strong anorexigenic effect: In vitro and in vivo studies","authors":"Veronika Strnadová ,&nbsp;Alena Karnošová ,&nbsp;Miroslava Blechová ,&nbsp;Barbora Neprašová ,&nbsp;Lucie Holá ,&nbsp;Anna Němcová ,&nbsp;Aneta Myšková ,&nbsp;David Sýkora ,&nbsp;Blanka Železná ,&nbsp;Jaroslav Kuneš ,&nbsp;Lenka Maletínská","doi":"10.1016/j.npep.2022.102319","DOIUrl":"10.1016/j.npep.2022.102319","url":null,"abstract":"<div><p>Prolactin-releasing peptide (PrRP) is an anorexigenic neuropeptide that attenuates food intake and increases energy expenditure. We designed three series of new lipidized PrRP31 analogs of different lengths of fatty acids attached at amino acids 1 or 11 directly or <em>via</em> linkers, part of them acetylated at the N-terminus and/or modified with dichlorophenylalanine (PheCl<sub>2</sub>) at the C-terminus. We tested their affinity for and activation of signaling pathways relevant to receptors GPR10, NPFF-R2, and NPFF-R1, effect on food intake in fasted or freely fed mice and rats, and stability in rat plasma. We aimed to select a strong dual GPR10/NPFF-R2 agonist whose affinity for NPFF-1 was not enhanced. The selected potent analog was then tested for body weight-lowering potency after chronic administration in mice with diet-induced obesity. PrRP31 analogs lipidized by monocarboxylic fatty acids showed strong dual affinity for both GPR10 and NPFF-R2 and activated MAPK/ERK1/2, Akt and CREB in cells overexpressing GPR10 and NPFF-R2. The selected analog stabilized at N- and C-termini and palmitoylated through the TTDS linker to Lys<sup>11</sup> is a powerful dual agonist GPR10/NPFF-R2 at not enhanced affinity for NPFF-R1. It showed strong anti-obesity properties in mice with diet-induced obesity and became a potential compound for further studies.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"98 ","pages":"Article 102319"},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9433160","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: 1
The stress-induced antinociceptive responses to the persistent inflammatory pain involve the orexin receptors in the nucleus accumbens 应激诱导的对持续炎症疼痛的镇痛反应涉及伏隔核中的食欲素受体
IF 2.9 3区 医学
Neuropeptides Pub Date : 2023-04-01 DOI: 10.1016/j.npep.2023.102323
Seyed Mohammadmisagh Moteshakereh , Mohammad Nikoohemmat , Danial Farmani , Elahe Khosrowabadi , Sakineh Salehi , Abbas Haghparast
{"title":"The stress-induced antinociceptive responses to the persistent inflammatory pain involve the orexin receptors in the nucleus accumbens","authors":"Seyed Mohammadmisagh Moteshakereh ,&nbsp;Mohammad Nikoohemmat ,&nbsp;Danial Farmani ,&nbsp;Elahe Khosrowabadi ,&nbsp;Sakineh Salehi ,&nbsp;Abbas Haghparast","doi":"10.1016/j.npep.2023.102323","DOIUrl":"10.1016/j.npep.2023.102323","url":null,"abstract":"<div><p><span><span><span>Stress suppresses the sense of pain, a physiological phenomenon known as stress-induced analgesia (SIA). Brain </span>orexin<span> peptides regulate many physiological functions, including wakefulness and nociception. The contribution of the orexinergic system within the </span></span>nucleus accumbens<span><span> (NAc) in the modulation of antinociception induced by forced swim stress (FSS) remains unclear. The present study addressed the role of intra-accumbal </span>orexin receptors<span><span> in the antinociceptive responses induced by FSS during the persistent inflammatory pain model in the rat. </span>Stereotaxic surgery<span> was performed unilaterally on 106 adult male Wistar rats weighing 250–305 g. Different doses (1, 3, 10, and 30 nmol/ 0.5 μl DMSO) of orexin-1 receptor (OX1r) antagonist (SB334867) or OX2 </span></span></span></span>receptor antagonist<span><span> (TCS OX2 29) were administered into the NAc five minutes before exposure to FSS for a 6-min period. The formalin test was carried out using formalin injection (50 μl; 2.5%) into the rat's </span>hind paw<span><span> plantar surface, which induces biphasic pain-related responses. The first phase begins immediately after formalin infusion and takes 3–5 min. Subsequently, the late phase begins 15–20 min after formalin injection and takes 20–40 min. The findings demonstrated that intra-accumbal microinjection of </span>SB334867 or TCS OX2 29 attenuated the FSS-induced antinociception in both phases of the formalin test, with the TCS OX2 29 showing higher potency. Moreover, the effect of TCS OX2 29 was more significant during the early phase of the formalin test. The results suggest that OX1 and OX2 receptors in the NAc might modulate the antinociceptive responses induced by the FSS.</span></span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"98 ","pages":"Article 102323"},"PeriodicalIF":2.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9433180","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: 3
Regional differences of tachykinin effects on smooth muscle and pacemaker potentials of the stomach, duodenum, ileum and colon of an emetic model, the house musk shrews 速激肽对催吐模型麝香鼩胃、十二指肠、回肠和结肠平滑肌和起搏电位影响的区域差异
IF 2.9 3区 医学
Neuropeptides Pub Date : 2023-02-01 DOI: 10.1016/j.npep.2022.102300
Julia Y.H. Liu , Yingyi Deng , Jessica C.M. Hui , Peng Du , Heidi S.H. Ng , Zengbing Lu , Lingqing Yang , Luping Liu , Aleena Khalid , M.P. Ngan , Dexuan Cui , Bin Jiang , S.W. Chan , John A. Rudd
{"title":"Regional differences of tachykinin effects on smooth muscle and pacemaker potentials of the stomach, duodenum, ileum and colon of an emetic model, the house musk shrews","authors":"Julia Y.H. Liu ,&nbsp;Yingyi Deng ,&nbsp;Jessica C.M. Hui ,&nbsp;Peng Du ,&nbsp;Heidi S.H. Ng ,&nbsp;Zengbing Lu ,&nbsp;Lingqing Yang ,&nbsp;Luping Liu ,&nbsp;Aleena Khalid ,&nbsp;M.P. Ngan ,&nbsp;Dexuan Cui ,&nbsp;Bin Jiang ,&nbsp;S.W. Chan ,&nbsp;John A. Rudd","doi":"10.1016/j.npep.2022.102300","DOIUrl":"10.1016/j.npep.2022.102300","url":null,"abstract":"<div><h3>Background and aims</h3><p>The contractile effects of tachykinins on the gastrointestinal tract are well-known, but how they modulate slow-waves, particularly in species capable of emesis, remains largely unknown. We aimed to elucidate the effects of tachykinins on myoelectric and contractile activity of isolated gastrointestinal tissues of the <em>Suncus murinus</em>.</p></div><div><h3>Methods</h3><p>The effects of substance P (SP), neurokinin (NK)A, NKB and selective NK<sub>1</sub> (CP122,721, CP99,994), NK<sub>2</sub> (SR48,968, GR159,897) and NK<sub>3</sub> (SB218,795, SB222,200) receptor antagonists on isolated stomach, duodenum, ileum and colon segments were studied. Mechanical contractile activity was recorded using isometric force displacement transducers. Electrical pacemaker activity was recorded using a microelectrode array.</p></div><div><h3>Results</h3><p>Compared with NKA, SP induced larger contractions in stomach tissue and smaller contractions in intestinal segments, where oscillation magnitudes increased in intestinal segments, but not the stomach. CP122,721 and GR159,897 inhibited electrical field stimulation-induced contractions of the stomach, ileum and colon. NKB and NK<sub>3</sub> had minor effects on contractile activity. The inhibitory potencies of SP and NKA on the peristaltic frequency of the colon and ileum, respectively, were correlated with those on electrical pacemaker frequency. SP, NKA and NKB inhibited pacemaker activity of the duodenum and ileum, but increased that of the stomach and colon. SP elicited a dose-dependent contradictive pacemaker frequency response in the colon.</p></div><div><h3>Conclusion</h3><p>This study revealed distinct effects of tachykinins on the mechanical and electrical properties of the stomach and colon vs. the proximal intestine, providing a unique aspect on neuromuscular correlation in terms of the effects of tachykinin on peristaltic and pacemaker activity in gastrointestinal-related symptoms.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"97 ","pages":"Article 102300"},"PeriodicalIF":2.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10510705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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