D_1类多巴胺受体对肾上腺素α受体介导的促动脉平滑肌细胞增殖作用的影响

目的观察D1类多巴胺受体对肾上腺素α受体介导的血管平滑肌(VSM)细胞增殖的影响。方法以去甲肾上腺素(NE)10-6~10-9mol/L刺激Sprague-Dawley(SD)大鼠主动脉分离的VSM细胞,观察在D1类多巴胺受体激动剂(Fenoldopam)10-5~10-8mol/L存在的情况下,NE促细胞增殖作用的变化,细胞增殖用3H-TdR掺入量表示。结果NE呈浓度依赖性的促进SD大鼠VSM细胞的增殖,该作用由肾上腺素α受体介导,酚妥拉明存在的情况下可消除NE的促增殖作用。Fenoldopam本身对VSM细胞增殖无影响,但Fenoldopam可通过D1类多巴胺受体减弱NE(10-6mol/L)介导的VSM细胞增殖;该实验结果得到了人VSM细胞实验结果的印证。结论D1类多巴胺受体对NE介导的促VSM细胞增殖具有抑制作用,该作用可能在高血压的发生、发展中发挥一定的作用。     

D3多巴胺受体对α肾上腺素能受体介导的促动脉平滑肌细胞增殖作用的影响

目的 观察D3多巴胺受体对肾上腺素α受体介导的血管平滑肌细胞(VSMC)增殖的影响.方法 用去甲肾上腺素(NE)刺激SD大鼠的VSMC,观察在D3受体激动剂(PD128907)存在的情况下,NE促增殖作用的变化,其中细胞增殖用3H-TdR掺入量表示.结果 NE通过肾上腺素α受体促进SD大鼠VSMC增殖,该作用呈现浓度依赖性关系.PD128907低浓度(10(-8)、10(-7) mol/L)对VSMC增殖无影响,但高浓度(10(-6)、10(-5) mol/L)却促进VSMC的增殖[PD128907 10(-6) mol/L=(4982±529)计数/min、PD128907 10(-5) mol/L=(5782±483)计数/min与对照=(3798±438)计数/min相比,P＜0.05],此作用可被α受体阻断剂酚妥拉明阻断.低浓度的PD128907(10(-7) mol/L)可通过D3受体减弱NE 10(-6) mol/L引起的VSMC增殖[NE 10(-6) mol/L=(6315±245)计数/min与NE 10(-6) mol/L PD128907 10(-7) mol/L=(4898±286)计数/min相比,P＜0.05.结论 D3受体对NE所致的VSMC增殖具有抑制作用,该作用可能在高血压的发生、发展中发挥作用.     

D_3多巴胺受体对α肾上腺素能受体介导的促动脉平滑肌细胞增殖作用的影响

目的观察D3多巴胺受体对肾上腺素α受体介导的血管平滑肌细胞(VSMC)增殖的影响。方法用去甲肾上腺素(NE)刺激SD大鼠的VSMC,观察在D3受体激动剂(PD128907)存在的情况下,NE促增殖作用的变化,其中细胞增殖用3H-TdR掺入量表示。结果NE通过肾上腺素α受体促进SD大鼠VSMC增殖,该作用呈现浓度依赖性关系。PD128907低浓度(10-8、10-7mol/L)对VSMC增殖无影响,但高浓度(10-6、10-5mol/L)却促进VSMC的增殖[PD128907 10-6mol/L=(4982±529)计数/min、PD128907 10-5mol/L=(5782±483)计数/min与对照=(3798±438)计数/min相比,P<0.05],此作用可被α受体阻断剂酚妥拉明阻断。低浓度的PD128907(10-7mol/L)可通过D3受体减弱NE 10-6mol/L引起的VSMC增殖[NE 10-6mol/L=(6315±245)计数/min与NE 10-6mol/L+PD128907 10-7mol/L=(4898±286)计数/min相比,P<0.05。结论D3受体对NE所致的VSMC增殖具有抑制作用,该作用可能在高血压的发生、发展中发挥作用。     

多巴胺D1类受体对胰岛素受体介导的血管平滑肌细胞增殖的影响

目的 观察多巴胺D1类受体对胰岛素受体介导的血管平滑肌细胞增殖的影响.方法 本研究以A10细胞为研究对象,观察刺激D1类受体对胰岛素促增殖作用的影响,并用免疫印迹研究D1类受体影响胰岛素作用的机制.细胞增殖作用采用[3H]胸腺嘧啶核苷(3H-TdR)掺入量表示.结果 胰岛素可促进A10细胞的增殖,该作用呈现浓度依赖性的.D1类受体激动剂Fenoldopam本身对A10细胞无增殖影响,但Fenoldopam通过D1类受体可完全阻断胰岛素介导的血管平滑肌细胞增殖作用.免疫印迹显示刺激D1类受体可降低胰岛素受体的蛋白表达,提示该机制可能参与了D1类受体对胰岛素受体作用的过程.结论 D1类受体对胰岛素受体介导的血管平滑肌细胞增殖具有抑制作用,该作用可能在高血压的发生发展中发挥一定作用.     

多巴胺D_1类受体对胰岛素受体介导的血管平滑肌细胞增殖的影响

目的观察多巴胺D1类受体对胰岛素受体介导的血管平滑肌细胞增殖的影响。方法本研究以A10细胞为研究对象,观察刺激D1类受体对胰岛素促增殖作用的影响,并用免疫印迹研究D1类受体影响胰岛素作用的机制。细胞增殖作用采用[3H]胸腺嘧啶核苷(3H-TdR)掺入量表示。结果胰岛素可促进A10细胞的增殖,该作用呈现浓度依赖性的。D1类受体激动剂Fenoldopam本身对A10细胞无增殖影响,但Fenoldopam通过D1类受体可完全阻断胰岛素介导的血管平滑肌细胞增殖作用。免疫印迹显示刺激D1类受体可降低胰岛素受体的蛋白表达,提示该机制可能参与了D1类受体对胰岛素受体作用的过程。结论D1类受体对胰岛素受体介导的血管平滑肌细胞增殖具有抑制作用,该作用可能在高血压的发生发展中发挥一定作用。     

多巴胺D3受体对胰岛素受体介导的促血管平滑肌细胞增殖作用的影响

目的 研究多巴胺D3受体对胰岛素受体介导的促血管平滑肌细胞增殖作用的影响.方法 以胚胎大鼠胸主动脉血管平滑肌细胞株(A10)为研究对象,观察在D3受体激动剂作用下,胰岛素受体促血管平滑肌细胞增殖作用的变化.利用[3H]-TdR细胞掺入实验观察细胞增殖状况,并利用免疫印迹法观察D3受体对胰岛素受体蛋白表达的影响,初步探讨D3受体影响胰岛素受体介导的促血管平滑肌细胞增殖作用的机制.结果 D3受体激动剂(PD128907)本身对血管平滑肌细胞增殖没有影响,但可抑制胰岛素受体介导的促血管平滑肌细胞增殖作用.刺激D3受体可降低胰岛素受体的表达,提示D3受体可能通过影响胰岛素受体的表达,从而影响胰岛素受体促血管平滑肌细胞增殖的过程.结论 D3受体对胰岛素受体介导的促血管平滑肌细胞增殖具有一定的抑制作用.     

胰岛素对肾脏近曲小管上皮细胞多巴胺D5受体表达和功能的影响

目的 观察胰岛素对肾脏近曲小管上皮(RPT)细胞多巴胺D5受体表达与功能的影响.方法 以RPT细胞与多巴胺D5受体转染的HEK293(HEK-D5)细胞为研究对象,观察胰岛素对D5受体表达与功能的影响,并在Wistar-Kyoto(WKY)大鼠与自发性高血压大鼠(SHR)的RPT细胞上比较这种影响的区别.观察在胰岛素[10-7 mmol/(L·24 h)]预先作用与否的情况下,D5受体(D1 类激动剂 Fenoldopam)对Na -K -ATP 酶活性的影响.结果 胰岛素可升高WKY的RPT细胞D5受体表达,该作用呈现作用浓度与时间依赖性;在SHR的RPT细胞却出现截然不同的现象,刺激胰岛素受体却降低了D5受体的表达;基础状态下,SHR的RPT细胞D5受体的表达明显低于WKY细胞.与单用Fenoldopam相比,在胰岛素(10-7 mmol/L/24 h)预先刺激的情况下,Fenoldopam降低Na -K -ATP酶的作用增强.结论 胰岛素可调节RPT细胞D5的表达和功能,该调节作用异常可能在高血压的发生发展中发挥一定作用.     

多巴胺D1类受体对血管平滑肌细胞胰岛素样生长因子1受体表达的影响

目的 观察多巴胺D1类受体对血管平滑肌细胞胰岛素样生长因子1(IGF-1)受体的影响.方法 以A10细胞为研究对象,免疫印迹观察刺激D1类受体对IGF-1受体表达的影响,并初步探讨D1类受体对IGF-1受体影响的机制.结果 刺激D1类受体可降低IGF-1受体的表达,D1类受体阻断剂可完全阻断D1类受体激动剂Fenoldopam对IGF-1受体的影响,免疫印迹显示运用蛋白激酶C(PKC)和促分裂原活化蛋白激酶(MAPK)阻断剂后,IGF-1受体表达恢复,提示PKC和MAPK途径可能参与了D1类受体对血管平滑肌细胞IGF-1受体的影响过程,在Wistar-Kyoto(WKY)大鼠和自发性高血压大鼠(SHR)血管平滑肌细胞中D1类受体激动剂Fenoldopam对IGF-1受体表达具有抑制作用,但该抑制作用在SHR细胞明显低于WKY细胞.结论 D1类受体对血管平滑肌细胞IGF-1受体表达具有抑制作用,该作用可能通过PKC和MAPK途径发挥一系列生理效应.     

多巴胺D3受体对胰岛素受体介导的促血管平滑肌细胞增殖作用的影响

目的研究多巴胺D3受体对胰岛素受体介导的促血管平滑肌细胞增殖作用的影响。方法以胚胎大鼠胸主动脉血管平滑肌细胞株(A10)为研究对象,观察在D3受体激动剂作用下,胰岛素受体促血管平滑肌细胞增殖作用的变化。利用[3H]-TdR细胞掺入实验观察细胞增殖状况,并利用免疫印迹法观察D3受体对胰岛素受体蛋白表达的影响,初步探讨D3受体影响胰岛素受体介导的促血管平滑肌细胞增殖作用的机制。结果D3受体激动剂(PD128907)本身对血管平滑肌细胞增殖没有影响,但可抑制胰岛素受体介导的促血管平滑肌细胞增殖作用。刺激D3受体可降低胰岛素受体的表达,提示D3受体可能通过影响胰岛素受体的表达,从而影响胰岛素受体促血管平滑肌细胞增殖的过程。结论D3受体对胰岛素受体介导的促血管平滑肌细胞增殖具有一定的抑制作用。     

多巴胺D_1类受体对血管平滑肌细胞胰岛素样生长因子1受体表达的影响

目的观察多巴胺 D_1类受体对血管平滑肌细胞胰岛素样生长因子1(IGF-1)受体的影响。方法以A10细胞为研究对象,免疫印迹观察刺激 D_1类受体对 IGF-1受体表达的影响,并初步探讨 D_1类受体对 IGF-1受体影响的机制。结果刺激 D_1类受体可降低 IGF-1受体的表达,D_1类受体阻断剂可完全阻断 D_1类受体激动剂Fenoldopam 对 IGF-1受体的影响,免疫印迹显示运用蛋白激酶 C(PKC)和促分裂原活化蛋白激酶(MAPK)阻断剂后,IGF-1受体表达恢复,提示 PKC 和 MAPK 途径可能参与了 D_1类受体对血管平滑肌细胞 IGF-1受体的影响过程,在 Wistar-Kyoto(WKY)大鼠和自发性高血压大鼠(SHR)血管平滑肌细胞中 D_1类受体激动剂 Fenoldopam 对IGF-1受体表达具有抑制作用,但该抑制作用在 SHR 细胞明显低于 WKY 细胞。结论 D_1类受体对血管平滑肌细胞 IGF-1受体表达具有抑制作用,该作用可能通过 PKC 和 MAPK 途径发挥一系列生理效应。     

Gastrin Receptor Pharmacology

C-terminally amidated gastrins act at cholecystokinin-2 receptors (CCK2R), which are normally expressed by gastric parietal and enterochromaffin-like (ECL) cells and smooth muscle; there is also extensive expression in the CNS where the main endogenous ligand is cholecystokinin. A variety of neoplasms express CCK2R, or splice variants, including neuroendocrine, pancreatic, medullary thyroid and lung cancers. Other products of the gastrin gene (progastrin, the Gly-gastrins) may stimulate cell proliferation but are not CCK2R ligands. Depending on the cell type, stimulation of CCK2R evokes secretion, increases proliferation and cell migration, inhibits apoptosis, and controls the expression of various genes. These effects are mediated by increased intracellular calcium and activation of protein kinase C, MAPkinase and other protein kinase cascades. There has been recent progress in developing CCK2R ligands that can be used for imaging tumours expressing the receptor. New antagonists have also been developed, and there is scope for using these for suppression of gastric acid and for treatment of neuroendocrine and other CCK2R-expressing tumours.     

Anti-N-Methyl-d-Aspartate Receptor Encephalitis

A case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with an atypical finding of transient increased intracranial pressure is reported. Anti-NMDAR encephalitis is an underrecognized, novel and treatable form of encephalitis being increasingly identified as an explanation of encephalitis in young adults. Management of these patients requires a multidisciplinary approach involving neurologists, internists, nursing and rehabilitation staff. It is important for internists to recognize this condition and consider it in the differential diagnosis of encephalopathy. Internists also need to be familiar with the clinical manifestations and the treatment of the disease as they have an important role in the care of these patients during their prolonged stay in the hospital. Increased intracranial pressure is an atypical and underrecognized finding that has been only noted in a previous review on this disorder. It may present a diagnostic or management challenge in patients with anti-NMDAR encephalitis.     

Peptide Receptor Imaging

Radiolabeled cell-surface peptide receptor-binding molecules are emerging as an important class of radiopharmaceuticals. Their binding to specific cell membrane receptors allows for noninvasive assessment of regional receptor proteomics in vivo. Information thus obtained can be used for diagnostic purposes and for predicting and monitoring response to treatment. This paradigm also applies to pulmonary diseases. In this review, available radiopharmaceuticals of great potential or already in clinical use for imaging of lung cancer, lung inflammation and infection and pulmonary embolism are discussed.In lung cancer, somatostatin receptor imaging by means of technetium-99m (^99mTc)-octreotide scintigraphy has proven useful for characterizing malignancy in solitary pulmonary nodules. Additionally, several radiopharmaceuticals targeting tyrosine-kinase, e.g. ^99mTc labeled epidermal growth factor and indium-111 (¹¹¹In)-diethylene triamine penta-acetic acid-trastuzumab, or G-protein coupled receptors, e.g. ^99mTc-bombesin, iodine-123-vasoactive intestinal peptide and ¹¹¹In-tetraazacyclododecane tetra-acetic acid (DOTA)-cholecystokinine-B, are being explored for their diagnostic as well as treatment monitoring potential.With the purpose of better evaluating the source of pulmonary embolism, as well as to differentiate acute from chronic deep venous thrombosis, several radiolabeled peptides targeting the glycoprotein IIb/IIIa fibrinogen receptor found on activated platelets have been developed. Out of these, ^99mTc-P280 is now approved by the US Food and Drug Administration for scintigraphic imaging of suspected acute venous thrombosis in the lower extremities of patients.In the field of lung inflammation and infection, non-specific ¹¹¹In and ^99mTc-human polyclonal immunoglobulins have been successfully used to identify the presence and extent of Pneumocystis carinii, cytomegalovirus, Mycobaterium avium and fungal infections in patients with HIV infection. The clinical role of other radiopharmaceuticals such as ^99mTc-J001X, a nonpyrogenic acylated polygalactoside isolated from Klebsiella pneumoniae and binding with high affinity to CD11b and CD14 lipopolysaccharide receptors expressed on monocytes/macrophages, and ¹¹¹In-octreotide, binding to up-regulated somatostatin receptors on activated lymphocytes needs to be further defined.     

瞬时受体电位香草酸亚型1在心血管系统中的调节作用

瞬时受体电位香草酸亚型1属于瞬时受体电位通道家族,可被辣椒素激活,在全身多处器官组织表达。主要通过调节细胞内Ca2+离子浓度,从而发挥多功能细胞感受器功能。该篇综述主要介绍目前瞬时受体电位香草酸亚型1在心血管系统中的功能研究,主要表现在调节血管张力,高血压发生、心肌缺血中的保护作用及预防动脉粥样硬化、植物神经功能影响几个方面,有望为心血管疾病诊治提供新的靶点。     

胃癌雌激素受体和孕激素受体的检测及临床意义

目的：为了研究雌激素受体（Ｅｓｔｒｏｇｅｎ ｒｅｃｅｐｔｏｒ,ＥＲ）的孕激素受体（Ｐｒｏｇｅｓｔｅｒｏｎｅ ｒｅｃｅｐｔｏｒ,ＰｇＲ）在胃癌中的表达以及与临床病理学之间的关系。方法：我们采用免疫组织化学法对９１例胃癌作了测定。结果：９１例胃癌的ＥＲ,ＰｇＲ阳性率分别为３９．６％,４１．８％。在９１例胃癌中,分化好的腺癌细胞ＥＲ,ＰｇＲ阳性率均为４７．９％,高于分化差的癌细胞的ＥＲ,ＰｇＲ阳性率（３     

Endocannabinoid Receptor Antagonists

Obesity has been described as a global epidemic. Its increasing prevalence is matched by growing costs, not only to the health of the individual, but also to the medical services required to treat a range of obesity-related diseases. In most instances, obesity is a product of progressively less energetic lifestyles and the over-consumption of readily available, palatable, and highly caloric foods. Past decades have seen massive investment in the search for effective anti-obesity therapies, so far with limited success. An important part of the process of developing new pharmacologic treatments for obesity lies in improving our understanding of the psychologic and physiologic processes that govern appetite and bodyweight regulation. Recent discoveries concerning the endogenous cannabinoids are beginning to give greater insight into these processes. Current research indicates that endocannabinoids may be key to the appetitive and consummatory aspects of eating motivation, possibly mediating the craving for and enjoyment of the most desired, most fattening foods. Additionally, endocannabinoids appear to modulate central and peripheral processes associated with fat and glucose metabolism. Selective cannabinoid receptor antagonists have been shown to suppress the motivation to eat, and preferentially reduce the consumption of palatable, energy-dense foods. Additionally, these agents act to reduce adiposity through metabolic mechanisms that are independent of changes in food intake. Given the current state of evidence, we conclude that the endocannabinoids represent an exciting target for new anti-obesity therapies.