细菌脂多糖对NIH3T3细胞增生、胞内游离钙及cAMP浓度的影响

目的 :探讨细菌脂多糖 (lipopolysaccharide,L PS)对 NIH 3T3细胞增生、胞内游离钙及 c AMP浓度的影响。　方法 :以中性红比色法检测细胞生长 ,酚试剂法检测细胞蛋白质合成 ,并动态检测 L PS对胞内游离钙和 c AMP浓度的影响。　结果 :1微量 L PS可促进细胞生长及蛋白质合成 ;2 L PS作用后 3～ 5 min可使胞内游离钙浓度升高 ,作用 1 m in后使 c AMP浓度升高 ,并保持较高水平。　结论 :胞内游离钙 ([Ca2 ]i)及 c AMP是 L PS对 NIH3T3细胞作用过程中重要的信使分子     

Effects of nitric oxide donors on the afferent resting activity in the cephalopod statocyst

The effects of bath applications of the nitric oxide (NO) donors sodium nitroprusside (SNP), diethylamine sodium (DEA), 3-morpholinosydnonimine (SIN-1), and S-nitroso-N-acetyl-penicillamine (SNAP) on the resting activity (RA) of afferent crista fibers were studied in isolated statocysts of the cuttlefish Sepia officinalis. The NO donors had three different effects: inhibition, excitation, and excitation followed by an inhibition. The SNAP analog N-acetyl-DL-penicillamine (xSNAP; with no NO moiety) had no effect. When the preparation was pre-treated with the NO synthase inhibitor N(G)-nitric-L-arginine methyl ester HCl (L-NAME), the NO donors were still effective. When the preparation was pre-treated with the guanylate cyclase inhibitors methylene blue (M-BLU) or cystamine (CYS), NO donors had only excitatory effects, whereas their effects were inhibitory only when pre-treatment was with the adenylate cyclase inhibitors nicotinic acid (NIC-A), 2',3'-dideoxyadenosine (DDA), or MDL-12330A. When pre-treatment was with a guanylate and an adenylate cyclase inhibitor combined, NO donors had no effect; in that situation, the RA of the afferent fibers remained and the preparation still responded to bath applications of GABA. Selective experiments with statocysts from the squid Sepioteuthis lessoniana and the octopod Octopus vulgaris gave comparable results. These data indicate that in cephalopod statocysts an inhibitory NO-cGMP and an excitatory NO-cAMP signal transduction pathway exist, that these two pathways are the key pathways for the action of NO, and that they have only modulatory effects on, and are not essential for the generation of, the RA.     

Barrier function of porcine choroid plexus epithelial cells is modulated by cAMP-dependent pathways in vitro

In the present paper, we demonstrate that the barrier properties of primary cultured epithelial cells isolated from porcine choroid plexus are regulated by cAMP-dependent signal transduction pathways in vitro. Triggering cAMP-connected cascades in cell layers grown on permeable filters with cAMP-analogues or forskolin led to a significant increase of transepithelial electrical resistances and a pronounced reduction in the permeation rate of a 4 kDa-dextran probe. In dose-response experiments using the cAMP-analogue 8-(4-chlorophenylthio)-cAMP transepithelial electrical resistances were observed to increase above a threshold concentration ranging between 10(-5.5) and 10(-5) M. Additional impedance studies performed with confluent cell layers grown on gold-film electrodes revealed that the observed changes in transepithelial resistances and presumably also in macromolecular permeation rates were not entirely caused by a reinforcement of intercellular junctions but also contained contributions from changes in the cell-substrate adhesion pattern. These inherent contributions to the electrical resistance and macromolecular permeability are caused by a restricted diffusion pathway between basal plasma membrane and culture substrate that have to be considered in data analysis, especially when leaky cell layers on filter substrates with low pore densities are used.     

新生儿缺氧缺血性脑病脑脊液环磷酸腺苷变化及其临床意义

目的 探讨新生儿缺血缺氧性脑病(HIE)脑脊液(CSF)环磷酸腺苷(cAMP)变化及其临床意义。方法 采用法国:Immunotech公司提供的125I-cAMP放免药盒对86例HIE患儿进行脑脊液cAMP。结果 中、重度HIE组CSI-cAMP值较非HIE组明显降低,有显著差异(P<0.05);重度HIE患儿CSI-cAMP值较轻、中度患儿降低,差异具有显著性(P<0.05);恢复期较急性期CSF-cAMP值都有所升高,但无显著差异。结论 HIE时CSF-cAMP降低,病情愈重,降低愈明显。CSF-cAMP测定可作为HIE患儿判断病情的辅助指标。     

褪黑素对吗啡戒断大鼠脑内cAMP和cGMP含量的影响

目的 :观察褪黑素 (MT)对吗啡戒断大鼠不同脑区cAMP和cGMP含量的影响。方法 :以剂量递增法连续皮下注射吗啡建立吗啡依赖模型 ,采用放射免疫学方法测定脑内cAMP和cGMP的含量。结果 :(1)MT对大鼠吗啡戒断症状具有明显的抑制作用 ;(2 )与对照组比较 ,吗啡依赖大鼠的纹状体、间脑、中脑、脑桥和海马内cAMP含量显著增高 (P <0 0 5 ,P <0 0 1) ,cGMP含量显著下降 (P <0 0 5 ,P <0 0 1)。与吗啡依赖组比较 ,催促戒断大鼠海马和纹状体内cAMP的含量显著升高 (P <0 0 5 ) ,而cGMP含量显著下降 (P <0 0 5 ,P <0 0 1) ,其他部位则无明显变化 ;(3)褪黑素急性治疗可使吗啡戒断大鼠纹状体、间脑、中脑、脑桥和海马内cAMP含量明显下降 (P <0 0 5 ,P <0 0 1) ,cGMP含量明显增高 (P <0 0 5 ,P <0 0 1)。结论 :MT可显著抑制大鼠吗啡戒断反应 ,并与调节中枢cAMP和cGMP含量有关。     

PLC对ADP诱导的兔血小板cAMP的影响

目的　测定磷酯酶C(phospholipaseC,简称PLC,下同)对ADP诱导的兔血小板cAMP的影响,从而进一步阐明PLC抗血小板聚集作用的机制。方法　取家兔的PRP,除去红细胞,分别用生理盐水、ASA和不同剂量的PLC处理,以ADP诱导激活,采用三氯醋酸法制备血小板cAMP,再用放射免疫分析法分别测定cAMP含量。结果　家兔血小板经生理盐水处理后的cAMP含量为 ( 20 16±0 91 ) pmol/109platelets,而经生理盐水、ASA668μmol·L-1、5、10、15、20和25UPLC·ml-1各组处理,并以ADP激活的血小板,测得的cAMP含量分别为 13 85±1 14, 16 27±0 36, 18 74±0 55,19 80±0 52, 20 49±0 43, 22 55±0 61和 24 24±0 85(pmol/109 platelets)。以生理盐水作为对照,ASA668μmol·L-1、5、10、15、20和 25UPLC·ml-1剂量组对激活状态下血小板cAMP的含量有增加的作用,增加率 (% )分别为17 47, 35 31, 42 96, 47 94, 62 82, 75 02。结论　PLC使得ADP激活后的兔血小板cAMP水平提高(P<0 01),且呈剂量依赖性,表明PLC具有提高血小板中cAMP水平的作用。这可能是PLC抗血小板聚集作用的重要原因之一。     

青风藤及青藤碱对吗啡依赖小鼠位置偏爱效应及cAMP水平的影响

目的观察中药青风藤及其有效成分青藤碱对吗啡诱导的小鼠位置偏爱效应的影响及其与中枢cAMP水平的关系.方法连续给予吗啡 (9mg/kg, 1次/d,sc) 5d,引起小鼠产生显著的条件性位置偏爱效应.用两种方式给予青风藤醇提液(5,10g/kg, ig)和青藤碱 (60mg/kg, ig) ,即在训练阶段每天sc吗啡前 45min给予和在d 6测定位置偏爱前45min仅给药一次.大脑皮层cAMP含量采用放射免疫法测定. 结果吗啡对照组小鼠在伴药箱中停留的时间明显延长, 小鼠脑组织的cAMP水平亦显著升高. 青风藤或青藤碱连续用药可显著抑制吗啡引起的小鼠位置偏爱的形成,对小鼠已形成的条件性位置偏爱效应也具有一定的抑制作用.并能降低脑内cAMP含量.结论青风藤及青藤碱能消除吗啡产生的条件性位置偏爱,其作用机制与降低中枢cAMP水平有关.     

脱氢表雄酮增强双丁酰环磷酰苷促进细胞分化的作用及可能机制

目的　观察脱氢表雄酮 (DHEA)是否能增强cAMP的类似物双丁酰环磷酰苷 (DbcAMP)促进神经突起的形成和生长及可能的机制。方法　利用NG10 8 15细胞这一具有神经元形态和功能的细胞系 ,在药物处理后 ,倒置显微镜下观察突起的生长状况 ,并测定突起的长度和有突起的细胞数 ;明胶酶谱分析NG10 8 15细胞在药物处理后 ,上清的基质金属蛋白酶 (MMP)MMP 9和MMP 2的分泌和酶的活性的变化。结果　①DHEA和DbcAMP可抑制NG10 8 15细胞的增殖 ;②DHEA可增强DbcAMP促进NG10 8突起生长的作用。Db cAMP可以诱导NG10 8细胞突起的形成和生长 ,而DHEA收稿日期 :2 0 0 4-0 2 -0 3 ,修回日期 :2 0 0 4-0 4-19作者简介 :廖　红 ( 1965 -) ,女 ,副教授 ,博士 ,研究方向 :分子药理、神经药理 ,Tel:0 2 5 83 5 93 3 74;E mail:liaohong5 6@hotmail.com与DbcAMP同时作用 ,NG10 8 15细胞突起的长度明显增加 ,而且有突起的细胞数也明显增多 ,DHEA的剂量越高 ,这种促NG10 8 15细胞突起生长的作用越明显。③基质金属蛋白酶参与神经元的分化。DbcAMP能诱导MMP 9和MMP 2的分泌 ,与之相比 ,DHEA +DbcAMP使NG10 8 15细胞的MMP 9和MMP 2的分泌明显增多 ,且具有剂量依赖关系。结论　DHEA具有增强DbcAMP促进NG10 8 15细胞突起形成和生长的作用     

Emerging pharmacological therapies for erectile dysfunction

There are new and novel therapies emerging in the field of erectile dysfunction, both centrally acting and peripherally acting agents delivered orally, intracavernosally or topically. Pharmacological targets include the enzyme phosphodiesterase Type 5 (PDE5), adrenergic receptors, prostaglandin receptors and guanyl cyclase.