P2Y13受体在神经系统的研究进展

ATP是维持机体细胞正常代谢所必须的能量载体,也是一种重要的神经递质。"嘌呤受体"是指ATP及其代谢产物ADP、AMP和腺苷所结合的受体。Burnstock等(1978年)将嘌呤受体分为P1和P2受体两类,P1受体又称腺苷受体;P2受体分为P2X(离子通道受体)和P2Y(G蛋白偶联受体)受体。由于分子克隆技术的迅速发展,迄今已从人体组织细胞     

神经系统P2Y受体功能研究进展

ATP是维持机体细胞正常代谢所必须的能量载体,但同时也是一种重要的神经递质.1978年,Bumstock等[1]将ATP受体分为P1和P2两类受体:P1受体又称腺苷受体;P2受体分为P2X(离子通道受体)和P2Y(G蛋白偶联受体).     

P2X7介导的小胶质细胞形态和受体表达的变化

目的:研究P2X7受体介导的小胶质细胞形态和受体表达的变化,探讨P2X7受体信号通路及其下游过程。方法:运用ATP刺激原代小胶质细胞,免疫细胞化学观察P2X7受体介导的细胞形态和受体表达的变化;建立表达P2X7受体的单克隆细胞模型,免疫细胞化学观察ATP刺激下P2X7受体介导的细胞形态和受体表达的变化。结果:ATP刺激下小胶质细胞和P2X7-HEK293细胞的突起变短,形态变圆,体积缩小;随着ATP刺激量的增加,P2X7受体的表达逐渐增加。结论:P2X7受体介导了小胶质细胞形态的变化。     

ATP通过P2Y1受体引发脊髓背角星形胶质细胞[Ca2+]i升高和GFAP表达上调

目的 观察体外培养的背角星形胶质细胞P2Y1受体激活对其[Ca2 ]i的变化和GFAP表达的影响.方法 培养并纯化脊髓背角星形胶质细胞,采用免疫组织化学染色观察背角星形胶质细胞P2Y1受体及GFAP的表达,激光共聚焦技术观察星形胶质细胞[Ca2 ]i的变化.结果 体外培养的大鼠脊髓背角星形胶质细胞大多表达P2Y1受体;P2Y受体激动剂ATP、ADP、ADP-βs剂量依赖性促进星形胶质细胞[Ca2 ]i升高;10 μg/mL的ATP、ADP和ADP-βs显著增加胞内[Ca2 ]i,此作用可被特异性P2Y1受体拮抗剂MRS2179所阻断,并具量效关系.免疫组织化学染色结果显示,100 μg/mL的ATP、ADP和ADP-βs作用下,星形胶质细胞GFAP表达上升,此效应可被100 μg/mL的MRS2179所抑制.结论 体外培养的大鼠脊髓背角星形胶质细胞表达P2Y1受体;P2Y1受体介导了ATP、ADP及ADP-βs促进星形胶质细胞[Ca2]i升高和GFAP表达增强的过程.     

P2嘌呤受体与免疫和炎症

嘌呤受体分为P1和P2受体两大类.P1受体属G蛋白偶联受体家族,包括A1、 A_(2A)、 A_(2B)、 A_3四类,主要由腺苷激活;P2受体包括P2X和P2Y两类,P2X受体是一类离子型配体门控通道,已克隆出7个不同的P2X亚型(P2X_(1-7)),P2Y受体是一类与G蛋白偶联的代谢型受体,包括P2Y_1、 P2Y_2、 P2Y_4、 P2Y_6 、 P2Y_(11-14)受体.这些P2受体主要由核苷酸(ATP、 ADP和UTP等)激活.P2嘌呤受体在体内分布广泛,在免疫反应与炎症过程中起着重要的作用.     

脑内P2X7受体研究进展

三磷酸腺苷（ATP）是细胞供能和储能的物质,在研究中发现它还是中枢神经系统的一种重要神经递质。1970年Burnstock G证实ATP是非胆碱能和非肾上腺素能神经释放的神经递质,正式提出了神经元细胞膜表面存在嘌呤受体。1985年他将ATP结合的受体命名为嘌呤能受体,并将其分为P1（腺苷）、P2（腺嘌呤核苷酸）两大类受体。     

ATP门控离子通道P2X_7受体在中枢系统的表达与功能

正P2X受体是由ATP激发的离子通道,从中可渗透Na~+、K~+和Ca~(2+),这些蛋白参与一系列生理过程,包括调节突触传输、平滑肌收缩、化学递质分泌和免疫反应调控。P2X_7受体作为P2X受体家族最独特的成员,其与其它成员在结构和功能上有显著差异,属于低分子溶质转运的非选择性离子通道~([1-3])。P2X_7受体作为嘌呤能受体,与其它P2受体有明显     

三磷酸腺苷对N9小胶质细胞的损伤作用及其机制

目的:研究三磷酸腺苷(ATP)对N9小胶质细胞的损伤作用及其机制。方法:取对数生长期N9小胶质细胞,随机分为3组:(1)正常对照组:常规培养,不进行ATP处理;(2)ATP组:接种24 h后行ATP处理;(3)KN-62(P2X₇受体阻断剂)干预组:KN-62孵育30 min后行ATP处理,且KN-62存在于ATP作用整个过程。XTT法测各组N9小胶质细胞的活力;倒置相差显微镜观察细胞形态变化;流式细胞术检测细胞周期及凋亡;细胞免疫荧光检测P2X₇受体表达;Western blotting检测细胞P2X₇受体蛋白水平;ELISA检测细胞上清液中白细胞介素1β(IL-1β)含量。结果:500 μmol/L ATP和1 mmol/L ATP对细胞活力损伤程度较小,作用24 h后,细胞活力仍可达88.5%±5.5%和88.2%±8.4%。当ATP浓度达到或高于2 mmol/L时,细胞活力迅速降低,细胞发生皱缩,且随ATP作用时间延长,细胞活力逐渐降低,细胞密度逐渐减少,细胞皱缩程度加重,而KN-62干预后细胞活力较ATP组明显增多,细胞密度及形态明显好于ATP组。细胞周期及凋亡检测结果显示,ATP可使细胞周期阻滞于S期,细胞凋亡比例明显较对照组增多(P<0.01),KN-62干预可显著减轻ATP引起的细胞周期阻滞,细胞凋亡比例显著减少(P<0.01)。免疫荧光显示,ATP及KN-62干预对N9小胶质细胞上P2X₇受体的表达分布没有影响。Western blotting显示,正常对照组、ATP组及KN-62干预组间P2X₇受体蛋白水平没有明显差异(P＞0.05)。ELISA结果显示,ATP及KN-62干预对IL-1β的释放没有作用。结论:高剂量ATP可诱发N9小胶质细胞损伤,其机制可能与P2X₇受体介导的细胞周期阻滞和细胞凋亡有关,而与小胶质细胞的炎症反应无关。     

P2Y_6受体及其在神经系统疾病研究中的进展

<正>1978年Burnstock等发现了介导ATP神经递质信号转导的嘌呤受体,将其分为P2X1-7和P2Y1,2,4,6,11,12,13,14受体两类,其中P2X受体是离子通道受体,P2Y受体是G蛋白偶联受体。不同亚型P2Y受体通过不同G蛋白激活不同的细胞内信号转导通路,从而产生特定的生理功能。近年研究表明,P2Y6受体不仅参与了神经病理性疼痛的发生与维持,而且     

P2Y_(13)受体激活促进脊髓背角小胶质细胞钙浓度升高

目的:观察ADP对培养的脊髓背角小胶质细胞内Ca2+浓度([Ca2+]i)的影响及作用机制。方法:培养纯化新生SD大鼠脊髓背角小胶质细胞,免疫组化观察P2Y13受体表达,激光共聚焦显微镜检测ADP作用下,小胶质细胞[Ca2+]i的变化。结果:大鼠脊髓背角小胶质细胞表达P2Y13受体,ADP可导致培养的脊髓背角小胶质细胞[Ca2+]i快速增高,且呈现剂量依赖性;P2Y13受体拮抗剂MRS2211(100μmol/L)能基本阻断ADP的作用,而P2Y1受体拮抗剂MRS2179(100μmol/L)、P2Y12受体拮抗剂MRS2395(100μmol/L)均不影响ADP致小胶质细胞[Ca2+]i升高的效应。结论:ADP可能通过P2Y13受体途径,导致培养的脊髓背角小胶质细胞[Ca2+]快速升高。     

Spatio-temporal changes in the metabolic processes in the blood-tissue system in the terminal states of the organism

The role of synergism in diffusion of oxygen from erythrocyte into interstitial liquid and water filtration through the capillary wall was studied on the model using the following parameters: hydrostatic pressure on arterial and venous ends of the capillary (Pa and Pb), oncotic blood and tissue pressure (Pob and Pot), pore radius in the capillary (r), the number of pores in the capillary (n) per m2, amount of the liquid released from the capillary (q(x)), gas diffusion coefficient (D), time of erythrocyte movement in the capillary (T), speed of oxygen consumption (V), maximal distance with adequate V (Xmax), characteristic time of diffusion (Topt). It is shown that diffuse and convective components of the metabolic process have their own contribution and in changed conditions they redistribute. In increased number and diameter of hydravlic pores the greatest role in tissue saturation with oxygen belongs to convective metabolism, but in this situation tissues contain areas lacking oxygen.     

Changes in the edentate mandible in the elderly

Resorption of alveolar bone is the best recognized feature of mandibular aging in the edentate subject. The other consequences of the loss of teeth in the elderly are less well known. An anthropometric study of the mandible by antero-posterior and lateral radiographs of subjects older than 70 years both dentate and edentate but without any maxillo-mandibular dysmorphosis has been done to demonstrate the differences, which exist between the dentate and edentate mandible. The edentate mandibles showed a diminution in the height of the symphysis and increase in the height of the mandibular incisure. A diminution in the height of the body and an increase in the gonial angle in the significant manner. No significant difference was seen for the height of the ramus and the length of the mandible, the minimum width of the ramus and the bigonial width. The diminution in the height of the mandibular symphysis and of the body is explained by the resorption of the alveoli part of the mandible. The increase in the mandibular angle and the diminution in the height of the mandibular incisure may be explained by disequilibrium between the elevator and depressor muscles of the mandible, as a function of the elevator muscles or by the absence of the molar buttress.     

On the role of the lymphoid follicle-associated areas in the organization of the bursal follicle in the cloacal bursa in birds

The present paper contains data on the morphological modifications present in chicks which, after treatment with testosterone lasting 10 days (from the seventh to the seventeenth days after hatching), were killed on the 30th, 35th, 40th, 50th and 70th day of life; this interval of time might theoretically have allowed a gradual re-establishment of the bursal architecture. Examination of the bursae of Fabricus of the animals treated showed greatly varying pictures. The 2 main types of behaviour were the following: the histological pattern of certain bursae had been completely restored to normal. Others did not act in the same way but wide areas of their plicae proved to be devoid of lymphoid tissue and well-formed lymphoid follicles were observed only in certain places. These 2 kinds of behaviour, and particularly what we observed in the second case, might suggest that, since the lymphoid follicle-associated epithelial cells are the last to disappear after treatment with testosterone propionate and the follicles are restored only where these cells remain, the lymphoid follicle-associated epithelial cells may be considered to be responsible for the re-establishment of the bursal follicle.     

Changes in the adrenals in the sudden death syndrome in infants

Adrenal glands of 52 children dying from a syndrome of sudden death (SSD) and 14 children of the same age dying from acute viral respiratory infections (AVRI) with a long terminal period were studied. The following adrenal changes typical for the SSD were observed: low weight, decrease of the size of the definitive cortex and its zones, the appearance of numerous adenomatous growths in the definitive cortex and so-called giant cells in the fetal cortex, low secretory activity. The appearance of adenomas and giant cells in the presence of organ hypoplasia is a compensatory-hyperplastic adrenal response which attests to a long glucocorticoid deficiency in the SSD. It is suggested that the deficiency of these hormones leads to the metabolic disturbances in various organs, including brain, resulting in the narrowing of the range of homeostatic host responses; this may become the cause of sudden death when the clinical and morphological manifestations of AVRI are insignificant.