共查询到20条相似文献,搜索用时 15 毫秒
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T Wasinger 《Wiener klinische Wochenschrift》1989,101(23):821-824
Synthesis, conversion, specific binding sites for PGI2, PGE1 and PGD2 and adenylate cyclase activity were evaluated in rat brain microvessels. All PG's investigated enhance adenylate cyclase activity dose-dependently. PGE1 and PGD2 were the major PG's formed by microvessels, in contrast to rat aortic tissue, generating predominantly 6-keto-PGF1 alpha, the stable degradation product of PGI2. On the contrary, RIA demonstrates that rat cerebral microvessels form predominantly 6-keto-PGF1 alpha (from endogenous precursor), followed by PGE2 and PGD2. PG actions on microvasculature are supposed to be predominantly mediated by adenylate cyclase linked receptors and there is good evidence for a central role of PGI2 and PGD2 in local regulation of the microcirculation. 相似文献
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The calcitonin gene‐related peptide (CGRP) neuropeptide system is an important but still evolving target for migraine. A fundamental consideration for all of the current drugs in clinical trials and for ongoing development in this area is the identity, expression pattern, and function of CGRP receptors because this knowledge informs safety and efficacy considerations. In recent years, only the calcitonin receptor‐like receptor/receptor activity‐modifying protein 1 (RAMP1) complex, known as the CGRP receptor, has generally been considered relevant. However, CGRP is capable of activating multiple receptors and could have more than one endogenous receptor. The recent identification of the CGRP‐responsive calcitonin receptor/RAMP1 complex (AMY1 receptor – amylin subtype 1 receptor) in the trigeminovascular system warrants a deeper consideration of the molecular identity of CGRP receptor(s) involved in the pathophysiology, and thus potential treatment of migraine. This perspective considers some of the issues and implications. 相似文献
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L M Reid 《The Journal of laboratory and clinical medicine》1984,103(2):161-179
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Estrogen and its receptors in cancer 总被引:1,自引:0,他引:1
The involvement of estrogen and its receptors in the development of cancer has been known for years. However, the exact mechanism responsible is far from clear. The estrogen-mediated carcinogenic process is complicated by recent findings, which reveal that estrogens have multiple functions in cells, which can be either adverse or beneficial, and that the effects of estrogen may be cell-type or organ dependent. The estrogenic effect may be also greatly influenced by the state of two estrogen receptors, ERalpha and ERbeta. This review will discuss the role and function of estrogens and its receptors in cancers of three categories: (1) Breast cancer and gynecologic cancers, (2) Cancers of endocrine organs, (3) Lung cancer and cancers of digestive system. We will also review some novel treatments aiming to interfere with relevant pathways mediated by estrogens and its receptors. 相似文献
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K Abe K Yoshinaga M Suzuki T Mori T Seki 《Nihon rinsho. Japanese journal of clinical medicine》1968,26(8):1901-1907
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Yuhki K Ueno A Naraba H Kojima F Ushikubi F Narumiya S Oh-ishi S 《The Journal of pharmacology and experimental therapeutics》2004,311(3):1218-1224
The roles of prostaglandins (PGs) as mediators of inflammation have been extensively studied, and production of PGI2 and PGE2 at inflammatory sites has been reported. However, it has not yet been clarified which type of PG receptors has a major role in inflammatory exudation. To examine in vivo role of PG receptors in inflammatory exudation, we induced pleurisy in PG receptors (IP, EP1, EP2, EP3, or EP4) knockout mice by intrapleural injection of carrageenin. Pleural exudate accumulation in wild-type (WT) mice at 1 to 5 h, but not at 24 h, was significantly attenuated by the pretreatment with indomethacin, indicating that PGs are responsible for exudate formation at the early phase of pleurisy. Pleural exudation at 1 to 5 h in IP, EP2, or EP3 knockout mice, but not in EP1 and EP4 knockout, was significantly reduced compared with in WT mice. In the exudates, 6-keto-PGF1alpha and PGE2 were detected as the major PGs, each with its peak concentration at 3 h. In addition, involvement of bradykinin in the phenomenon was suggested by the fact that captopril, a kininase inhibitor, enhanced the exudate formation and increased the amount of 6-keto-PGF1alpha and PGE2 and that a bradykinin B2-receptor antagonist inhibited the exudate formation. In contrast, leukocyte migration into pleural cavity was not influenced by indomethacin-treatment nor by these receptor deficiencies. These results demonstrate participation of EP2 and EP3 along with IP in pleural exudate formation but not in leukocyte migration in carrageenin-induced mouse pleurisy. 相似文献
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Petrucci G De Cristofaro R Rutella S Ranelletti FO Pocaterra D Lancellotti S Habib A Patrono C Rocca B 《The Journal of pharmacology and experimental therapeutics》2011,336(2):391-402
Activated human platelets synthesize prostaglandin (PG) E(2), although at lower rate than thromboxane A(2). PGE(2) acts through different receptors (EP1-4), but its role in human platelet function remains poorly characterized compared with thromboxane. We studied the effect of PGE(2) and its analogs on in vitro human platelet function and platelet and megakaryocyte EP expression. Platelets preincubated with PGE(2) or its analogs were stimulated with agonists and studied by optical aggregometry. Intraplatelet calcium mobilization was investigated by the stopped flow method; platelet vasodilator-stimulated phosphoprotein (VASP), P-selectin, and microaggregates were investigated by flow cytometry. PGE(2) at nanomolar concentrations dose-dependently increased the slope (velocity) of the secondary phase of ADP-induced platelet aggregation (EC(50), 25.6 ± 6 nM; E(max) of 100 ± 19% increase versus vehicle-treated), without affecting final maximal aggregation. PGE(2) stabilized reversible aggregation induced by low ADP concentrations (EC(50), 37.7 ± 9 nM). The EP3 agonists, 11-deoxy-16,16-dimethyl PGE(2) (11d-16dm PGE(2)) and sulprostone enhanced the secondary wave of ADP-induced aggregation, with EC(50) of 48.6 ± 10 nM (E(max), 252 ± 51%) and 5 ± 2 nM (E(max), 300 ± 35%), respectively. The EP2 agonist butaprost inhibited ADP-induced secondary phase slopes (IC(50), 40 ± 20 nM). EP4 stimulation had minor inhibitory effects. 11d-16dm PGE(2) alone raised intraplatelet Ca(2+) and enhanced ADP-induced Ca(2+) increase. 11d-16dm PGE(2) and 17-phenyltrinor PGE(2) (EP3 > EP1 agonist) at nanomolar concentrations counteracted PGE(1)-induced VASP phosphorylation and induced platelet microaggregates and P-selectin expression. EP1, EP2, EP3, and EP4 were expressed on human platelets and megakaryocytes. PGE(2) through different EPs finely modulates human platelet responsiveness. These findings should inform the rational selection of novel antithrombotic strategies based on EP modulation. 相似文献
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Prostaglandin and thromboxane biosynthesis 总被引:16,自引:0,他引:16
We describe the enzymological regulation of the formation of prostaglandin (PG) D2, PGE2, PGF2 alpha, 9 alpha, 11 beta-PGF2, PGI2 (prostacyclin), and thromboxane (Tx) A2 from arachidonic acid. We discuss the three major steps in prostanoid formation: (a) arachidonate mobilization from monophosphatidylinositol involving phospholipase C, diglyceride lipase, and monoglyceride lipase and from phosphatidylcholine involving phospholipase A2; (b) formation of prostaglandin endoperoxides (PGG2 and PGH2) catalyzed by the cyclooxygenase and peroxidase activities of PGH synthase; and (c) synthesis of PGD2, PGE2, PGF2 alpha, 9 alpha, 11 beta-PGF2, PGI2, and TxA2 from PGH2. We also include information on the roles of aspirin and other nonsteroidal anti-inflammatory drugs, dexamethasone and other anti-inflammatory steroids, platelet-derived growth factor (PDGF), and interleukin-1 in prostaglandin metabolism. 相似文献
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The purpose of this study was to characterize the type of adrenergic receptor(s) involved in both prostaglandin (PG) synthesis and the contractile response elicited by adrenergic receptor agonists in the rabbit aorta. The synthesis of prostacyclin as measured by the production of 6-keto-PGF1 alpha was assessed in vitro after exposing the aortic rings to different adrenergic agonists. Norepinephrine (NE), selective alpha 1 adrenergic receptor agonists methoxamine (MET), phenylephrine (PHE) and cirazoline (CIR) and the alpha 2 adrenergic receptor agonists UK 14304 (UK) and xylazine (XYL), but not the beta adrenergic receptor agonist isoproterenol (ISP), enhanced 6-keto-PGF1 alpha synthesis in a concentration-dependent manner with following order of potency: NE greater than UK 14304 greater than XYL greater than PHE greater than MET greater than CIR. The NE-induced increased in 6-keto-PGF1 alpha synthesis was attenuated by the alpha 1 adrenergic receptor antagonists prazosin (PZ) and corynanthine (COR) and by the alpha 2 adrenergic receptor antagonists rauwolscine (RW) and yohimbine (YOH). MET-induced 6-keto-PGF1 alpha synthesis was reduced by PZ and COR but not by RW. UK-induced 6-keto-PGF1 alpha synthesis was reduced by RW, YOH, and PZ, which also acts as alpha-2B receptor antagonist, but not by COR. In rabbit aortic rings, adrenergic agonists produced contraction with the following order of potency: NE greater than PHE greater than MET greater than CIR greater than UK greater than XYL.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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文思思 《国际输血及血液学杂志》2015,38(2)
神经纤毛蛋白(NRP)是信号素(Sema)家族和血管内皮生长因子(VEGF)家族的共同受体.通过Sema家族和VEGF家族,NRP分别在神经元和心血管发育中起着重要作用.NRP通过与其配体的其他受体结合,形成复合体,如Sema家族的神经丛蛋白和VEGF家族的VEGF受体(VEGFR)2,进而加强其信号传导,从而调节一些生理过程,其中最重要的为胞迁移.研究证实,NRP在一些疾病病理相关过程中亦起着重要作用.NRP可高表达于多种肿瘤细胞,这提示NRP是肿瘤治疗的一个潜在靶点.此外,在免疫系统中,NRP通过Sema3A参与免疫负调节,为治疗自身免疫疾病提供新思路.笔者拟就NRP及其配体的免疫调节机制进行综述如下. 相似文献
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Measurement of oxidized LDL and its soluble receptors 总被引:1,自引:0,他引:1
Kume N 《Nihon rinsho. Japanese journal of clinical medicine》2004,62(6):1132-1135
Oxidized LDL and its receptors play important roles in atherosclerotic progression and atherosclerotic plaque rupture, by enlarging the lipid core and weakening the fibrous cap. Oxidized LDL, in fact, induces foam cell transformation of macrophages, production of matrix metalloproteinases(MMPs), and apoptosis of smooth muscle cells. Oxidized LDL concentrations in circulating blood in humans have been shown to be elevated in diabetes and atherosclerotic vascular diseases, especially acute coronary syndrome. Lectin-like oxidized LDL receptor-1(LOX-1) is a cell surface receptor for oxidized LDL, which is abundantly expressed in atherosclerotic plaques and is involved in oxidized LDL-induced MMP production and apoptosis. Soluble LOX-1 concentration in human blood also have been shown to be elevated in coronary heart diseases especially in acute coronary syndrome. 相似文献
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Mori Y 《Nihon rinsho. Japanese journal of clinical medicine》2001,59(3):431-436
alpha, beta, gamma-MSH and ACTH are derived from the same precursor, POMC(proopiomelanocortin), and are classified as melanocortin. alpha-MSH plays an important role in the regulation of appetite and energy expenditure via central melanocortin receptor, melanocortin 4 receptor(MC4R), which is expressed mainly in hypothalamus. alpha-MSH or its analogue shows inhibitory effect on appetite and inversely MC4R antagonist stimulates appetite. MC4R knock-out mice has adult-onset obesity and decreased energy expenditure. POMC gene expression in hypothalamus is partially regulated by leptin. Agouti-related peptide(AgRP), a homologue of agouti peptide and antagonist of MC3R and MC4R, is expressed in human brain and may act as a inhibitor of alpha-MSH. From the genetical aspect, the region near POMC gene, 2p23, is one of the susceptibility loci of human obesity. POMC gene mutations are found in two families, where mutations in both alleles cause human obesity, red hair, adrenal dysfunction, due to alpha-MSH and ACTH deficiencies. In morbidity obese patients, heterozygous MC4R gene mutations are found among 4% of them. These results suggest the importance of melanocortin and its receptors on appetite regulation in human. 相似文献
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Arakawa T Higuchi K Fujiwara Y Watanabe T Tominaga K 《Nihon rinsho. Japanese journal of clinical medicine》2002,60(8):1618-1625
After discovery of H. pylori, management of peptic ulcer disease (PUD) is getting much easier. However, four thousands a year still died caused by this disease in Japan. Ten to twenty percent of the non-NSAIDs ulcer could be expected to remain after complete eradication of H. pylori; The number could be still 100,000-200,000 a year in Japan. Furthermore, NSAIDs ulcer would not decrease in number in the post-H. pylori era. Recurrence of ulcer is related to the quality of ulcer healing. Deficiency of prostaglandins(PG) in the mucosa is another main reason than H. pylori infection of poor quality of ulcer healing. Therefore, a PG analogue may be a most reasonable tool for treatment of H. pylori-negative PUD including NSAIDs ulcer, but is often poorly tolerated because of diarrhea and abdominal pain. The mucosal damage caused by NSAIDs is also gastric acid-dependent and so, an H2-receptor antagonist is to some extent effective although the efficacy is far behind of that with a PG-analogue. Recently, a proton-pump inhibitor has been reported to exert the same effect as a PG-analogue in healing of gastroduodenal mucosal damage caused by NSAIDs and the superior effect in preventing recurrence of the damage with better tolerance. This results suggest that strong acid inhibition is highly effective for such damage. Whether such strong acid inhibition causes disturbance of absorption of NSAIDs is not clear, which might result in poor antiinflammatory effect. Elderly patients often have tendency of constipation and less possibility of pregnancy. Therefore, a PG-analogue may be not only safe but also more favorable for such patients. 相似文献
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K. Birkenmeier I. Janke W.‐H. Schunck C. Trimpert T. Krieg M. Landsberger U. Völker S. B. Felix A. Staudt 《European journal of clinical investigation》2008,38(12):902-909
Background After ischaemia and during reperfusion, rat hearts release cardiodepressive substances that are putatively cyclooxygenase‐2‐dependent. The present study analyses the mechanisms by which these substances mediate their effect downstream of cyclooxygenase‐2. Materials and methods After 10 min of global stop‐flow ischaemia, isolated rat hearts were reperfused and post‐ischaemic coronary effluent was collected over a period of 30 s. Non‐ischaemic effluent collected before ischaemia was used as a control. We investigated the effect of the effluents on cell shortening and Ca++‐metabolism, by application of fluorescence microscopy of field‐stimulated adult rat cardiomyocytes incubated with fura‐2. Cells were pre‐incubated with inhibitors of protein kinase A and C and with antagonists of protein kinase A‐dependent prostaglandin receptors. We examined the expression of prostaglandin receptors in cardiomyocytes by Western blotting. Results In contrast to non‐ischaemic effluent, post‐ischaemic effluent induced reduction of Ca++ transient and cell shortening in the cardiomyocytes. In contrast to protein kinase C inhibitor Myr‐PKC [19–27], the protein kinase A inhibitor Rp‐cAMPS completely blocked the effect of post‐ischaemic effluent. Furthermore, we determined a cyclic adenosine monophosphate increase in cardiomyocytes that were pre‐incubated with post‐ischaemic effluent. The antagonist of prostaglandin E‐receptor EP2 AH6809 and the antagonist of receptor subtype EP4 AH23848 attenuated the effect of post‐ischaemic effluent in contrast to other antagonists of prostaglandin D and I receptors, which did not influence the effect. In lysates of adherend cardiomyocytes, expression of prostaglandin D, E and I receptors was detected by Western blotting. Conclusions The effect of post‐ischaemic effluent is mediated by the protein kinase A‐dependent prostaglandin‐receptor subtypes EP2 and EP4 downstream of cyclooxygenase‐2. 相似文献
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目的通过测定B淋巴细胞刺激因子(BLyS)及其受体在单克隆丙球蛋白血症中的表达水平,探讨BLyS及其受体与多发性骨髓瘤(MM)的关联性。方法流式细胞术对9例不同型别的MM患者及11例良性单克隆丙球蛋白血症(MGUS)患者,以及7名正常人外周B淋巴细胞表面BLyS及其3种受体BLyS受体(BAFFR)、穿膜蛋白活化物(TACI)、B细胞成熟抗原(BCMA)进行分析。并运用酶联免疫吸附试验(ELISA)对20例MM患者、23例MGUS患者、20名健康者血清BAFF水平进行检测。结果 MM、MGUS及正常对照组外周B淋巴细胞膜表面均表达BAFFR,但各组间差异无统计学意义(P〉0.05)。膜表面受体结合BAFF情况比较,各组间差异有统计学意义(P〈0.05)。MM组结合能力最强。TACI在MM及MGUS组低表达,其中MM组与正常对照组比较差异有统计学意义(P〈0.05)。胞浆BCMA高表达,MM组与正常对照组或与MGUS组比较差异均有统计学意义(P〈0.05)。血清BLyS水平MM组高于MGUS组(P〈0.05),MGUS组高于正常对照组(P〈0.05)。结论 BLyS及其受体BAFFR、TACI、BCMA可能与MM的发病机制有关。血清BLyS可作为MM的实验室辅助诊断指标之一。 相似文献
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目的:成年哺乳动物中枢神经系统损伤后,少突胶质细胞和髓鞘来源的几种抑制蛋白能够显著抑制其再生,通过与共同的Nogo-66受体结合而发挥抑制轴突再生的作用。近来发现Nogo-A及髓鞘相关糖蛋白还有另外的不同于Nogo-66受体途径,为进一步研究中枢神经系统损伤后再生提供了新思路。本文就Nogo-A、髓鞘相关糖蛋白、少突胶质细胞髓鞘糖蛋白及其受体的研究进展作一综述。资料来源:应用计算机检索PUBMED1981-01/2004-05期间的相关文章,检索词为“Nogo-A,MAG,OMgp,NgR”,并限定文章语言种类为English。资料选择:选取实验为各类型中枢神经系统损伤的大鼠模型的相关实验,进行初审,删除明显不符合动物模型实验的研究,然后查找余下的文献全文,进一步判断是否为随机动物模型实验。纳入标准:①随机动物模型试验,无论是否为单盲、双盲或非盲法。②平行对照组为脊髓未受损伤的大鼠动物模型,治疗组为中枢神经系统受损的大鼠模型。排除标准:明显不随机的动物模型试验或非动物模型研究;质量评价主要考察资料的真实性,试验设计是否合理,观测检验过程是否严格,统计学处理是否有说服力;重复研究或Meta分析类文章。资料提炼:共检索到30篇相关文献,排除的6篇文献中,2篇是重复的同一研究,4篇不符合大鼠模型试验。共24篇文献符合纳入标准,其中7篇涉及Nogo-A蛋白,8篇涉及髓鞘相关糖蛋白,5篇涉及少突胶质细胞髓鞘糖蛋白,5篇涉及Nogo-66受体及其他受体。资料综合:Nogo-A包含Nogo-66和amino-Nogo两个功能性结构域,对轴突生长均有抑制作用。髓鞘相关糖蛋白不仅对成年轴突生长具有抑制作用,且可以促进新生神经元轴突生长。少突胶质细胞髓鞘糖蛋白是糖基磷脂酰肌醇锚合蛋白,富含亮氨酸重复片段结构域,参与蛋白间的相互作用,发挥DNA修复、RNA剪接、细胞间黏附及信号转导等功能。结论:成年哺乳动物中枢神经系统受损后,几种主要的抑制蛋白与共受体结合而发挥抑制轴突再生的作用,为进一步研究中枢神经系统损伤后再生做铺垫。 相似文献