| 1 | Mechanisms of antinociceptive effects of ouabain in combination with neostigmine in the rat显示文摘BACKGROUND: It has been previously shown that intrathecal administration of either ouabain or neostigmine can produce antinociceptive effects. Moreover, ouabain and neostigmine are differently associated with acetylcholine. OBJECTIVE: It has been hypothesized that intrathecal administration of ouabain, in combination with neostigmine, can produce antinociceptive synergistic effects. Atropine, as a competitive antagonist, was pre-injected to verify the mechanisms of action. DESIGN, TIME AND SETTING: This study was a randomized, controlled, animal experiment, performed at the State Key Laboratory of Oncology in Southern China between May 2006 and February 2007. MATERIALS: A total of 102 healthy, adult, Sprague Dawley rats were included. Ouabain and neostigmine (Sigma, USA), as well as atropine (Tanabe Seiyaku, Japan), were also used. METHODS: Varied doses of ouabain, neostigmine, and a combination of the two were intrathecally injected into rats. Six rats were allotted for each dose group. Intrathecal pretreatment with atropine was tested 10 minutes prior to intrathecal administration of neostigmine or the combination of ouabain and neostigmine. MAIN OUTCOME MEASURES: Tail-flick tests were performed to measure tail-flick latency (seconds) prior to and after administration. The response in the tail-flick test was expressed as the percentage of maximum possible effect (% MPE), where % MPE = [tail-flick latency after administration (seconds) -mean baseline value for tail-flick latency]/[10 seconds - the mean baseline value for tail-flick latency (seconds)] × 100%. RESULTS: Rat spinal intrathecal administration of either ouabain or neostigmine alone produced antinociceptive effects in a dose-dependent manner. Intrathecally administration of neostigmine (0.05, 0.1, 0.3 μg ) in combination with ouabain (1 μg ) produced enhanced antinociceptive effects, with a % MPE of 29%, 78%, and 95%, respectively (P < 0.05). Intrathecally administration of 0.3 μg neostigmine (% MPE: 45%), in combination with 1 μg ouabain (% MPE: 27%) produced potent antinociceptive effects (% MPE: 95%). Intrathecally pre-injected atropine antagonized the antinociceptive effects of neostigmine (3 μg), or a combination of ouabain (1 μg) and neostigmine (0.3 μg) (P < 0.01). CONCLUSION: Rat spinal intrathecal administration of either ouabain or neostigmine alone produced dose-dependent antinociceptive effects. Ouabain enhanced the antinociceptive effects of neostigmine. Atropine antagonized the antinociceptive effects of neostigmine or the combination of ouabain and neostigmine. This occurs possibly due to the fact that atropine is a competitive antagonist of the muscarinic acetylcholine receptors. | Handong Ouyang Qiang Li Weian Zeng Weixiong He Peizong Wang | 2008 | Neural Regeneration Research2008，3，7： | 1 |
| 3 | Increased dopamine and its receptor dopamine receptor D1 promote tumor growth in human hepatocellular carcinoma显示文摘Background:Dopamine and dopamine receptor D1(DRD1),a member of the dopamine receptor family,have been indicated to play important roles in cancer progression,but dopamine secretion in hepatocellular carcinoma(HCC)and the effects of DRD1 on HCC remain unclear.This study was designed to explore the contribution of the dopaminergic system to HCC and determine the relationship between DRD1 and prognosis in HCC patients.Methods:The dopamine metabolic system was monitored using enzyme-linked immunosorbent assays(ELISAs).The expression of DRD1 was detected by microarray analysis,immunohistochemistry(IHC),and quantitative real-time PCR(qRT-PCR).Stable DRD1 knockout and overexpression cell lines were established for investigation.Transwell,colony formation,and Cell Counting Kit 8(CCK8)assays were performed to assess the malignant behaviors of cancer cells.The cAMP/PI3K/AKT/cAMP response element-binding(CREB)signaling pathway was evaluated by Western blot.This pathway,which is agitated by DRD1 in striatal neurons,had been proven to participate in tumor progression.Xenograft HCC tumors were generated for in vivo experiments.Results:Dopamine secretion increased locally in HCC due to an imbalance in dopamine metabolism,including the upregulation of dopa decarboxylase(DDC)and the downregulation of monoamine oxidase A(MAOA).Dopamine promoted the proliferation and metastasis of HCC.DRD1 was highly expressed in HCC tissues and positive DRD1 expression was related to a poor prognosis in HCC patients.The upregulation of DRD1 agitated malignant activities,including proliferation and metastasis in HCC by regulating the cAMP/PI3K/AKT/CREB pathway,and the downregulation of DRD1 had opposing effects.The effects of dopamine on HCC was reversed by depleting DRD1.SCH23390,a selective DRD1 antagonist,inhibited the proliferation and metastasis of HCC cells both in vitro and in vivo.Conclusion:Dopamine secretion was locally increased in HCC and promoted HCC cell proliferation and metastasis.DRD1 was found to exert positive effects on HCC progression and play a vital role in the dopamine system,and could be a potential therapeutic target and prognostic biomarker for HCC. | Yan Yan Jiahao Pan Yonghua Chen Wei Xing Qiang Li Dongyin Wang Xiaoshuang Zhou Jingdun Xie Changhong Miao Yunfei Yuan Weian Zeng Dongtai Chen | 2020 | Cancer Communications2020，40，12： | 1 |
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