TRPV

TRPV
  • 文章类型: Journal Article
    鳄鱼的性别取决于鸡蛋的温度,因此发育中的胚胎在发育的关键时期暴露。温度依赖性性别决定是所有鳄鱼和许多其他爬行动物类群中发生的过程。对不同种类的鳄鱼和短吻鳄的人工培养温度的研究确定了导致性别比改变的特定温度范围。它还揭示了产生相等数量的男性和女性的精确温度阈值,以及幼体性别可能发生变化的特定发育期。这篇综述将研究近几十年来阐明的鳄鱼性别决定机制的分子基础。它将关注与此过程相关的许多模式和理论。此外,我们将研究孵化后由于孵化温度的变化而产生的后果,以及气候变化对显示基于温度的性别决定的鳄鱼的潜在好处和危险。
    The sex of crocodilians is determined by the temperature to which the eggs, and hence the developing embryo are exposed during critical periods of development. Temperature-dependent sex determination is a process that occurs in all crocodilians and numerous other reptile taxa. The study of artificial incubation temperatures in different species of crocodiles and alligators has determined the specific temperature ranges that result in altered sex ratios. It has also revealed the precise temperature thresholds at which an equal number of males and females are generated, as well as the specific developmental period during which the sex of the hatchlings may be shifted. This review will examine the molecular basis of the sex-determination mechanism in crocodilians elucidated during recent decades. It will focus on the many patterns and theories associated with this process. Additionally, we will examine the consequences that arise after hatching due to changes in incubation temperatures, as well as the potential benefits and dangers of a changing climate for crocodilians who display sex determination based on temperature.
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  • 文章类型: Journal Article
    眼内压和外压的改变与青光眼的发病机制密切相关,创伤性视网膜损伤(TRI),和其他视网膜疾病,近几十年来,据报道视网膜神经元表达多个机械敏感通道(MSCs)。然而,MSCs在视觉功能和压力相关视网膜疾病中的作用尚不清楚.本文将重点介绍对K+具有渗透性的MSCs的多样性和功能意义,Na+,和Ca2+,主要包括大钾通道(BK);双孔结构域钾通道TRAAK和TREK;Piezo;上皮钠通道(ENaC);以及视网膜光感受器中的瞬时受体电位通道香草酸TRPV1,TRPV2和TRPV4,双极细胞,水平单元格,无长突细胞,和神经节细胞.大多数MSC不直接介导脊椎动物视网膜中的视觉信号。另一方面,一些研究表明,MSCs在生理条件下可以开放,调节视网膜神经元的活动。虽然这些数据合理地预测了视觉和机械信号的交叉,视网膜光路如何处理内源性和外源性机械刺激是不确定的。
    Alterations in intraocular and external pressure critically involve the pathogenesis of glaucoma, traumatic retinal injury (TRI), and other retinal disorders, and retinal neurons have been reported to express multiple mechanical-sensitive channels (MSCs) in recent decades. However, the role of MSCs in visual functions and pressure-related retinal conditions has been unclear. This review will focus on the variety and functional significance of the MSCs permeable to K+, Na+, and Ca2+, primarily including the big potassium channel (BK); the two-pore domain potassium channels TRAAK and TREK; Piezo; the epithelial sodium channel (ENaC); and the transient receptor potential channels vanilloid TRPV1, TRPV2, and TRPV4 in retinal photoreceptors, bipolar cells, horizontal cells, amacrine cells, and ganglion cells. Most MSCs do not directly mediate visual signals in vertebrate retinas. On the other hand, some studies have shown that MSCs can open in physiological conditions and regulate the activities of retinal neurons. While these data reasonably predict the crossing of visual and mechanical signals, how retinal light pathways deal with endogenous and exogenous mechanical stimulation is uncertain.
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  • 文章类型: Journal Article
    尿液储存和排泄需要尿路和中枢神经系统(CNS)的相互作用网络,这是由膀胱中的水和膀胱颈的出口介导的,尿道和尿道外括约肌。通过相互沟通和协调,排尿系统最终显示出开关样的活动模式。在颈胸和腰骶椎,下尿路(LUT)的脊髓反射途径接受来自尿路上皮的机械感觉输入以调节膀胱收缩活动,从而自愿控制排尿。上述任何水平的损害都可能导致下尿路功能障碍(LUTD),给患者和社会带来了巨大的负担。嘌呤能受体和瞬时受体电位(TRP)通道的特异性表达被认为在下尿路的尿排泄中起重要作用。本文综述了有关排尿反射的知识,并描述了TRP通道在排尿过程中的作用和功能。
    BACKGROUND: Urine storage and excretion require a network of interactions in the urinary tract and the central nervous system, which is mediated by a reservoir of water in the bladder and the outlet to the bladder neck, urethra, and external urethral sphincter. Through communicating and coordinating each other, micturition system eventually showed a switch-like activity pattern.
    CONCLUSIONS: At cervicothoracic and lumbosacral spine, the spinal reflex pathway of the lower urinary tract (LUT) received mechanosensory input from the urothelium to regulate the bladder contraction activity, thereby controlled urination voluntarily. Impairment of above-mentioned any level could result in lower urinary tract dysfunction, placed a huge burden on patients and society. Specific expression of purinergic receptors and transient receptor potential (TRP) channels are thought to play an important role in urinary excretion in the LUT.
    CONCLUSIONS: This article reviewed the knowledge about the voiding reflex and described the role and function of TRP channels during voiding.
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  • 文章类型: Journal Article
    背景:Afidopyropen是一种新型的杀虫剂,在诸如桃子蚜虫的吸吮昆虫和诸如七斑女虫的天敌之间具有高选择性。然而,Afidopyropen的选择性作用机制尚不清楚.
    结果:第1-4龄幼虫和成虫C.septempunctata的阿非多巴霉素的LC50值比成虫M.persicae高372至7267倍以上。尽管persicae中细胞色素P450的活性比septempunctata中的细胞色素P450的活性高6.1至7.5倍,后者具有更高的羧酸酯酶(CarEs)和谷胱甘肽S-转移酶(GSTs)活性,七叶梭菌和马尾梭菌的粗酶表现出与阿非多霉素相似的代谢效率。分子对接结果表明,无花果酚对桃子分枝杆菌的香草酸型瞬时受体电位(TRPV)通道的结合亲和力(-9.1kcal/mol)高于对七星菌的结合亲和力(-8.2kcal/mol)。无花果素对七叶草TRPV通道的EC50值(41360nM)比桃分枝杆菌(2.08nM)高19885倍。
    结论:我们的研究结果表明,马尾藻和C.septempunctataTRPV通道对afidopyropen的敏感性差异在afidopyropen的高选择性中起关键作用。这些发现提供了新的见解,以了解afidopyropen对害虫和天敌的选择性机制,并为化学控制和生物防治的协调应用提供了理论支持。本文受版权保护。保留所有权利。
    BACKGROUND: Afidopyropen is a novel insecticide with high selectivity between sucking insects such as the peach aphids Myzus persicae and natural enemies like the seven-spotted lady beetle Coccinella septempunctata. However, the mechanisms of selective action for afidopyropen remain unknown.
    RESULTS: The LC50 values of afidopyropen to the 1st-4th instar larvae and adult C. septempunctata were 372- to more than 7267-fold higher than that to adult M. persicae. Though the activity of cytochrome P450s in M. persicae was 6.1- to 7.5-fold higher than that in C. septempunctata, the latter has much higher activities of carboxylesterase (CarEs) and glutathione S-transferases (GSTs), and the crude enzyme of C. septempunctata and M. persicae showed similar metabolism efficiency to afidopyropen. Molecular docking results demonstrated that afdopyropen showed higher binding affinity to the vanilloid-type transient receptor potential (TRPV) channel of M. persicae (-9.1 kcal/mol) than to that of C. septempunctata (-8.2 kcal/mol). And the EC50 value of afdopyropen to the TRPV channel of C. septempunctata (41 360 nM) was 19 885-fold higher than that in M. persicae (2.08 nM).
    CONCLUSIONS: Our results demonstrated that the significantly different sensitivity of M. persicae and C. septempunctata TRPV channel to afidopyropen play a key role in the high selectivity of afidopyropen. These findings provide new insights into the selective mechanisms of afidopyropen against insect pests and natural enemies as well as the theory support for coordinated application of chemical control and biological control. © 2024 Society of Chemical Industry.
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  • 文章类型: Journal Article
    肥胖是一种复杂的疾病,肥胖的发病率在全球范围内以惊人的速度继续上升。特别是,儿童超重和肥胖发病率的增加是一个主要的健康问题。然而,肥胖的潜在机制仍不清楚,几种减肥方法的疗效有限.作为一种重要的钙渗透温敏阳离子通道,瞬时受体电位香草酸(TRPV)离子通道直接参与热,机械-,和化学感应反应。TRPV离子通道活性的调节可以改变离子通道的生理功能,导致神经退行性疾病,慢性疼痛,癌症,和皮肤病。近年来,越来越多的研究表明,TRPV离子通道在代谢器官中大量表达,包括肝脏,脂肪组织,骨骼肌,胰腺,和中枢神经系统,与各种代谢疾病有关,包括肥胖和糖尿病。此外,作为脂肪细胞代谢病理生理学的重要过程,脂肪细胞分化在肥胖中起关键作用。在这次审查中,我们关注TRPV离子通道在脂肪细胞分化中的作用,以拓宽肥胖防治策略的思路.
    Obesity is a complex disorder, and the incidence of obesity continues to rise at an alarming rate worldwide. In particular, the growing incidence of overweight and obesity in children is a major health concern. However, the underlying mechanisms of obesity remain unclear and the efficacy of several approaches for weight loss is limited. As an important calcium-permeable temperature-sensitive cation channel, transient receptor potential vanilloid (TRPV) ion channels directly participate in thermo-, mechano-, and chemosensory responses. Modulation of TRPV ion channel activity can alter the physiological function of the ion channel, leading to neurodegenerative diseases, chronic pain, cancer, and skin disorders. In recent years, increasing studies have demonstrated that TRPV ion channels are abundantly expressed in metabolic organs, including the liver, adipose tissue, skeletal muscle, pancreas, and central nervous system, which has been implicated in various metabolic diseases, including obesity and diabetes mellitus. In addition, as an important process for the pathophysiology of adipocyte metabolism, adipocyte differentiation plays a critical role in obesity. In this review, we focus on the role of TRPV ion channels in adipocyte differentiation to broaden the ideas for prevention and control strategies for obesity.
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  • 文章类型: Journal Article
    瞬时受体电位香草素(TRPV)通道是TRP通道超家族的成员,它们是离子通道,可感知机械和渗透刺激,并参与跨细胞膜的Ca2信号传导。TRPV通道在维持生物体的正常功能方面发挥着重要作用,TRPV通道功能的缺陷或异常会导致一系列疾病,包括心血管,神经和泌尿系统疾病。青光眼是一组慢性进行性视神经疾病,可在眼睛的前后段组织中发生病理变化,包括睫状体,小梁网,施莱姆的运河,和视网膜.TRPV通道在这些组织中表达并在青光眼中起各种作用。在这篇文章中,我们回顾了青光眼发病机制的各个方面,TRPV通道的结构和功能,TRPV通道与全身性疾病的关系,TRPV通道与眼部疾病的关系,尤其是青光眼,并提出了未来的研究方向。这些信息将有助于我们进一步了解TRPV通道,并为青光眼和视神经损害的治疗提供新的思路和靶点。
    Transient receptor potential vanilloid (TRPV) channels are members of the TRP channel superfamily, which are ion channels that sense mechanical and osmotic stimuli and participate in Ca2+ signalling across the cell membrane. TRPV channels play important roles in maintaining the normal functions of an organism, and defects or abnormalities in TRPV channel function cause a range of diseases, including cardiovascular, neurological and urological disorders. Glaucoma is a group of chronic progressive optic nerve diseases with pathological changes that can occur in the tissues of the anterior and posterior segments of the eye, including the ciliary body, trabecular meshwork, Schlemm\'s canal, and retina. TRPV channels are expressed in these tissues and play various roles in glaucoma. In this article, we review various aspects of the pathogenesis of glaucoma, the structure and function of TRPV channels, the relationship between TRPV channels and systemic diseases, and the relationship between TRPV channels and ocular diseases, especially glaucoma, and we suggest future research directions. This information will help to further our understanding of TRPV channels and provide new ideas and targets for the treatment of glaucoma and optic nerve damage.
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  • 文章类型: Journal Article
    脊索器官是昆虫中存在的微型感觉器官。脊索器官依赖于瞬时受体电位(TRP)通道。瞬时受体电位香草素(TRPV)通道是唯一确定的可作为杀虫剂靶标的TRP。通过与TRPV通道绑定,针对脊索器官的杀虫剂会引发钙离子的流入,导致脊索器官功能异常,以达到消灭害虫的目的。TRPV通道在昆虫的各个发育阶段和组织部位高表达,在昆虫的整个生活史中起着重要作用。在这次审查中,我们将讨论TRPV通道的结构和类型以及它们在不同物种中的遗传关系。我们还系统地回顾了TRPV通道作为杀虫剂靶标的最新进展,证明TRPV通道可作为新型高效杀虫剂的靶标。
    Chordotonal organs are miniature sensory organs present in insects. Chordotonal organs depend on transient receptor potential (TRP) channels. Transient receptor potential vanilloid (TRPV) channels are the only TRPs identified that can act as targets of insecticides. By binding with TRPV channels, insecticides targeting the chordotonal organs trigger the inflow of calcium ions, resulting in abnormal function of the chordotonal organ to achieve the goal of eliminating pests. TRPV channels are highly expressed in various developmental stages and tissue parts of insects and play an important role in the whole life history of insects. In this review, we will discuss the structure and types of TRPV channels as well as their genetic relationships in different species. We also systematically reviewed the recent progress of TRPV channels as insecticide targets, demonstrating that TRPV channels can be used as the target of new high-efficiency insecticides.
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  • 文章类型: Journal Article
    淋巴管能够通过基于淋巴集热器壁中的淋巴肌的自发收缩的内在机制维持淋巴形成和推进。暴露于高渗或低渗环境可以严重影响内在收缩率,因此改变淋巴流量。在这项工作中,我们的目标是定义这种反应背后的假定受体。在离体大鼠膈标本中进行了功能实验,该标本含有自发收缩的淋巴管,这些淋巴管暴露于高渗液或低渗液中。淋巴管受到TRPV4、TRPV1和VRAC通道阻滞剂的挑战,已知对渗透压和/或细胞肿胀的变化有反应,并由淋巴管表达。结果表明,对高渗性环境的正常反应是收缩率和淋巴流量的稳定降低,可以通过用卡沙西平阻断TRPV1通道来预防。对下磨牙环境的反应包括收缩率增加的早期阶段,其次是下降。早期阶段通过用DCPIB阻断VRAC而取消,而阻断TRPV4主要导致早期反应的延迟。总的来说,我们的数据表明,三个通道的合作可以塑造淋巴管在收缩频率和淋巴流量方面的反应,TRPV1和VRACs的作用突出。
    Lymphatic vessels are capable of sustaining lymph formation and propulsion via an intrinsic mechanism based on the spontaneous contraction of the lymphatic muscle in the wall of lymphatic collectors. Exposure to a hyper- or hypo-osmolar environment can deeply affect the intrinsic contraction rate and therefore alter lymph flow. In this work, we aimed at defining the putative receptors underlying such a response. Functional experiments were conducted in ex vivo rat diaphragmatic specimens containing spontaneously contracting lymphatic vessels that were exposed to either hyper- or hypo-osmolar solutions. Lymphatics were challenged with blockers to TRPV4, TRPV1, and VRAC channels, known to respond to changes in osmolarity and/or cell swelling and expressed by lymphatic vessels. Results show that the normal response to a hyperosmolar environment is a steady decrease in the contraction rate and lymph flow and can be prevented by blocking TRPV1 channels with capsazepine. The response to a hyposmolar environment consists of an early phase of an increase in the contraction rate, followed by a decrease. The early phase is abolished by blocking VRACs with DCPIB, while blocking TRPV4 mainly resulted in a delay of the early response. Overall, our data suggest that the cooperation of the three channels can shape the response of lymphatic vessels in terms of contraction frequency and lymph flow, with a prominent role of TRPV1 and VRACs.
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  • 文章类型: Journal Article
    背景:低雄激素症是勃起功能障碍(ED)的原因。血管平滑肌细胞的收缩和舒张受TRPV1-4通道调控。然而,雄激素不足对TRPV1-4的影响及其与勃起功能的关系尚不清楚。
    目的:揭示低雄激素血症是否通过影响TRPV1-4在大鼠海绵体中的表达而影响勃起功能。
    方法:8周龄雄性SD大鼠(N=36)随机分为6组(n=6):假手术,阉割,阉割+睾酮替代,假手术+转染,去势+转染,和去势+空转染。阉割四周后,将20μL携带TRPV4基因的慢病毒载体(1×108TU/mL)注射到转染组的阴茎海绵体组织中。转染后一周,最大海绵体内压(ICPmax)/平均动脉压(MAP)和TRPV1-4,磷酸化eNOS(p-eNOS)/eNOS的含量,测量各组阴茎海绵体组织中的一氧化氮(NO)。
    结果:在低雄激素条件下,TRPV4在年夜鼠阴茎海绵体内皮细胞中的表达急剧降低,导致p-eNOS/eNOS和NO含量降低,这可能会抑制勃起功能。
    结果:在大鼠阴茎海绵体组织中,TRPV1-4在内皮细胞和平滑肌细胞的细胞膜上表达。ICPmax/MAP和TRPV4、p-eNOS/eNOS的含量,与假手术组相比,去势组大鼠阴茎海绵体组织中NO终产物亚硝酸盐水平明显降低(P<0.05)。ICPmax/MAP和TRPV4、p-eNOS/eNOS的含量,与去势组相比,去势+转染组大鼠阴茎海绵体组织中NO终产物亚硝酸盐水平明显提高(P<0.01)。
    结论:上调阴茎海绵体组织中TRPV4的表达可能是治疗雄激素不足所致ED的可行方法。
    TRPV4在ED中的具体机制需要通过雄激素受体或TRPV4基因敲除实验进一步验证。
    结论:低雄激素血症可能通过降低大鼠阴茎海绵体组织中TRPV4的表达而引起ED。上调阴茎海绵体组织中TRPV4的表达可以增加p-eNOS/eNOS的比值和NO水平,改善去势大鼠的勃起功能。
    Hypoandrogenism is a cause of erectile dysfunction (ED). Vascular smooth muscle cell contraction and relaxation are regulated by TRPV1-4 channels. However, the influence of hypoandrogenism on TRPV1-4 and its relationship with erectile function remain unclear.
    To reveal whether hypoandrogenism affects erectile function by influencing TRPV1-4 expression in the corpus cavernosum of rats.
    Male Sprague-Dawley rats (N = 36) aged 8 weeks were assigned to 6 groups at random (n = 6): sham operation, castrated, castrated + testosterone replacement, sham operation + transfection, castrated + transfection, and castrated + empty transfection. Four weeks after castration, 20 μL of lentiviral vector (1 × 108 TU/mL) carrying the TRPV4 gene was injected into the penile cavernous tissue of the transfection groups. One week after transfection, the maximum intracavernous pressure (ICPmax)/mean arterial pressure (MAP) and the content of TRPV1-4, phosphorylated eNOS (p-eNOS)/eNOS, and nitric oxide (NO) in penile cavernous tissue of each group were measured.
    Under low androgen conditions, TRPV4 expression in endothelial cells in the rat penile cavernosum was sharply reduced, resulting in a decrease in p-eNOS/eNOS and NO content, which could inhibit erectile function.
    In rat penile cavernous tissue, TRPV1-4 was expressed in the cell membranes of endothelial cells and smooth muscle cells. The ICPmax/MAP and the content of TRPV4, p-eNOS/eNOS, and NO end product nitrite level in rat penile cavernous tissue was markedly reduced in the castrated group as compared with the sham group (P < .05). The ICPmax/MAP and the content of TRPV4, p-eNOS/eNOS, and NO end product nitrite level in rat penile cavernous tissue were markedly improved in the castrated + transfection group vs the castrated group (P < .01).
    Upregulation of TRPV4 expression in penile cavernosum tissue might be a viable therapeutic for ED caused by hypoandrogenism.
    The specific mechanism of TRPV4 in ED needs to be further verified by androgen receptor or TRPV4 gene knockout experiments.
    Hypoandrogenism may cause ED by reducing the expression of TRPV4 in rat penile cavernous tissue. Upregulation of TRPV4 expression in penile cavernous tissue can increase the ratio of p-eNOS/eNOS and NO levels and ameliorate the erectile function of castrated rats.
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  • 文章类型: Journal Article
    本研究旨在评估含有solasodine的茄子乙醇提取物(EESTF)治疗大鼠慢性缩窄性损伤(CCI)引起的神经性疼痛的疗效。在TRPV1受体上进行了solasodine结合的三维(3D)模拟研究,IL-6和TNF-α结构。对于体内理由,对行为的评估,生物化学,并在CCI诱导的大鼠神经病理性疼痛模型后设计组织学变化。在第7、14和21天,CCI显着增加机械,热,和冷异常性疼痛,同时产生功能缺陷。IL-6,TNF-α,TBARS,MPO水平也有所上升。过氧化氢酶和还原型谷胱甘肽的SOD水平也降低。普瑞巴林(30mg/kg,oral),solasodine(25mg/kg,oral),和EESTF(100和300毫克/千克,口服)显着减少CCI引起的行为和生化变化(P<0.05)。EESTF的保护性质也通过组织学分析得到证实。辣椒素,TRPV1受体激动剂,取消了以前使用EESTF的抗伤害作用。从对接研究的观察来看,solasodine充当TRPV1的拮抗剂,而solasodine对TNF-α和IL-6的对接得分据报道为-11.2和-6.04kcal/mol,分别。EESTF的减弱作用可能与其对TRPV1的拮抗作用、抑制细胞因子、和抗炎和抗氧化特性。
    This study aimed to assess the efficacy of ethanolic extract of Solanum torvum L. fruit (EESTF) containing solasodine in treating chronic constriction injury (CCI)-induced neuropathic pain in rats. Three-dimensional (3D) simulation studies of solasodine binding were conducted on the TRPV1 receptor, IL-6, and TNF-α structures. For in vivo justification, an assessment of behavioral, biochemical, and histological changes was designed after a CCI-induced neuropathic pain model in rats. On days 7, 14, and 21, CCI significantly increased mechanical, thermal, and cold allodynia while producing a functional deficit. IL-6, TNF-α, TBARS, and MPO levels also increased. SOD levels of catalase and reduced glutathione levels also decreased. Administration of pregabalin (30 mg/kg, oral), solasodine (25 mg/kg, oral), and EESTF (100 and 300 mg/kg, oral) significantly reduced CCI-induced behavioral and biochemical changes (P < 0.05). The protective nature of EESTF was also confirmed by histological analysis. Capsaicin, a TRPV1 receptor agonist, abolished the antinociceptive effects of EESTF when used previously. From the observations of the docking studies, solasodine acted as an antagonist at TRPV1, whereas the docking scores of solasodine against TNF-α and IL-6 were reported to be -11.2 and -6.04 kcal/mol, respectively. The attenuating effect of EESTF might be related to its antagonistic effects on TRPV1, suppression of cytokines, and anti-inflammatory and antioxidant properties.
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