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1.
Serotonin (5-HT) is a mediator (through 5-HT1P receptors) of slow EPSPs in myenteric ganglia of the small intestine. The effect of 5-HT can be mimicked by elevating cAMP; therefore, we tested the hypothesis that the slow EPSP-like response to 5-HT is cAMP-mediated. Guinea pig gut was enzymatically dissociated; myenteric ganglia remained intact and were collected by filtration. Neurons in the isolated ganglia retained their ability to manifest the slow EPSP-like response to 5-HT. Exposure to 5-HT raised the ganglionic level of cAMP (ED50 0.3 μM). This effect was not antagonized by the 5-HT1P antagonist, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (100.0 μM), or mimicked by the 5-HT1P agonist, 5-hydroxyindalpine (10.0 μM). Increases in cAMP were also evoked by the 5-HT1 agonist, 5-carboxyamidotryptamine (10.0 μM), the 5-HT2 agonist, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 1.0–10.0 μM), and by the 5-HT4 agonists, renzapride (1.0–10.0 μM) and 5-methoxytryptamine (1.0–10.0 μM); however, neither the 5-HT1/5-HT2 antagonists, spiperone, methysergide, and methiothepin, nor the 5-HT4 antagonist, tropisetron (ICS 205–930; 10.0 μM), were able to inhibit the rise in cAMP evoked by these compounds or by 5-HT (0.1–10.0 μM). The 5-HT-evoked elevation of cAMP was antagonized by ketanserin (10.0 μM), which also blocked the effects of 5-methoxytryptamine and DOI, but not those of renzapride. The effective concentration of DOI, however, was higher than that needed for activation of 5-HT2 receptors, and Northern analysis using a cDNA probe encoding the rat 5-HT2 receptor failed to reveal the presence of 5-HT2 mRNA in myenteric ganglia, although it hybridizes with mRNA of the right size in the guinea pig brain. Compounds that failed to change levels of cAMP or to antagonize the action of 5-HT included 8-hydroxy-di-n-propylamino tetralin, R58639, R88226, and sumatriptan. It is concluded that the receptor responsible for the 5-HT-induced rise in cAMP in ganglia isolated from the guinea pig myenteric plexus is not a known subtype of 5-HT receptor. Since the pharmacology of this novel receptor is different from that of the slow EPSP-like response to 5-HT, the receptor probably does not mediate the slow EPSP. © 1993 Wiley-Liss, Inc. 相似文献
2.
慢性低氧大鼠肺动脉内皮素mRNA的表达及定位 总被引:1,自引:0,他引:1
目的:探讨慢性低氧大鼠肺动脉内皮素-1基因表达及分布。方法:采用生物素标记cRNA探针,对Wistar大鼠肺动脉进行原位杂交。结果:低氧1周组及低氧2周组大鼠大部分肺动脉内皮细胞ET-1mRNA表达呈阳性信号,而对照组大鼠仅极少数阳性信号(P<0.01);低氧1周组大鼠部分显示强阳性信号。低氧1周组及低氧2周组大鼠部分肺动脉平滑肌细胞呈现ET-1mRNA表达阳性信号,而对照组大鼠则无阳性信号表达(P<0.01及0.05)。结论:慢性低氧对大鼠肺动脉ET-1分泌的影响是在基因转录水平进行,且主要细胞定位在肺动脉内皮细胞,此外还包括肺动脉平滑肌细胞。 相似文献
3.
以钒基核苷酸复合物为核酸酶抑制剂,从人胚组织中制备总RNA,所得产品几乎不含DNA和蛋白质,经过分离Poly(A)~ mRNA,证明制品有合成cDNA的完整功能,方法比较简捷,适于大量制备以满足分离mRNA 之需,并讨论了此法的优缺点。 相似文献
4.
We studied the alteration of intracellular signal transduction using quantitative autoradiography of the second messenger system in order to clarify the mechanisms of delayed neuronal damage in the remote areas of rat brain after transient focal ischemia. Chronological changes of [3H]forskolin binding sites were measured to demonstrate the striatal-nigral pathway after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by 3 h, 6 h, 1 day, 3 days, 1 week, 2 weeks and 4 weeks of recirculation. [3H]Forskolin binding sites were found to be markedly decreased in the lateral segment of the caudate putamen supplied by the occluded MCA after 90 min of ischemia with no recirculation. On the contrary, there was no alteration on day 1, but 3 days after ischemic insult, marked reduction of [3H]forskolin binding sites was observed in the ipsilateral substantia nigra which lay outside the ischemic areas. This postischemic delayed phenomenon observed in the substantia nigra developed concurrently with 45Ca accumulation, which was detected there in our previous study. The delayed reduction of [3H]forskolin binding sites in the substantia nigra observed in the present study indicates that striatonigral terminal degeneration at presynaptic sites is caused by precedent ischemic damage of the ipsilateral caudate putamen and that exo-focal postischemic neuronal death is caused by a transsynaptic process associated with the ischemic foci. 相似文献
5.
大鼠肝细胞Ⅰ,Ⅲ型前胶原基因表达及PDGF的影响 总被引:3,自引:1,他引:2
目的观察大鼠肝细胞Ⅰ,Ⅲ型前胶原基因的表达及PDGF对其表达的影响.方法应用原位杂交技术检测分离培养的SD大鼠肝细胞(n=30)内Ⅰ,Ⅲ型前胶原基因的表达.同时观察10μg/L(n=30)和30μg/L(n=30)PDGF促进前胶原基因表达的作用.测定基因表达颗粒总面积占细胞总面积的百分比,并作比较分析.结果无论正常肝细胞或是在两种浓度的PDGF存在时,肝细胞内均可见到Ⅰ,Ⅲ型前胶原基因的表达.正常肝细胞Ⅰ,Ⅲ型前胶原基因表达面积的百分比(%)为77±19和75±21;加10μg/LPDGF后为115±19和112±10,而加30μg/L后为152±34及181±28,且在后者中表达明显增强(P<005及P<001).结论PDGF在转录水平上促进肝细胞胶原的合成. 相似文献
6.
2型糖尿病患者外周血白细胞iNOSmRNA表达的变化及意义 总被引:1,自引:0,他引:1
目的研究2型糖尿病DM患者外周血白细胞中iNOSmRNA表达的变化及其与糖尿病肾病DN发生、发展的关系。方法101例2型DM患者,根据尿微量白蛋白排泄率和血肌酐水平分为单纯DM组和不同的DN组,用原位杂交法检测外周血白细胞iNOSmRNA表达的阳性细胞的百分率,并与21例健康体检者进行比较。结果早期DN组白细胞iNOSmRNA表达的百分率明显高于对照组、DM组及晚期DN组(P<0.001)。结论外周血白细胞iNOSmRNA表达的变化参与了DN的发生、发展。 相似文献
7.
Treatment of PC12 cells with nerve growth factor (NGF) produces a rapid and transient increase in calcium uptake into the cells. The increased uptake is maximal after 5 minutes of NGF treatment, but after 15 minutes of NGF treatment, no such increase can be observed. The effect of NGF is partially inhibited by blockers of L-type calcium channels. K-252a, an alkaloid-like kinase inhibitor that usually is found to inhibit the actions of NGF on PC12 cells, produces an increase in calcium uptake similar to, but smaller than, that seen with NGF. NGF had no effect on calcium release under these conditions. 相似文献
8.
Hideaki Ban Hiroyuki Kato Tsutomu Araki Hideaki Fujikura Yoshinari Hasegawa Kyuya Kogure 《Brain research》1994,646(2)
We investigated the effects of age and naftidrofuryl oxalate (Naftidrofuryl), a 5-HT2 antagonist, on neurotransmission and transduction systems in the gerbil hippocampus using quantitative autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]cyclohexyl-adenosine (CHA), [3H]MK-801, and [3H]muscimol were used to label muscarinic acetylcholine, adenosine A1, N-methyl-d-aspartate (NMDA), and γ-aminobutyric acid-A (GABAA) receptors, respectively. [3H]PN200-110 labeled L-type Ca2+ channels. [3H]Forskolin, [3H]cyclic adenosine monophosphate (cAMP), [3H]phorbol 12,13-dibutyrate (PDBu), and [3H]inositol 1,4,5-triphosphate (IP3) were used to label adenylate cyclase, cAMP-dependent protein kinase, protein kinase C (PKC), and IP3 receptors, respectively. Approximately 20% reductions in [3H]QNB, [3H]forskolin, and [3H]PDBu binding were observed in the hippocampus of 9-month-old gerbils in comparison with 5-week-old gerbils. Treatment with Naftidrofuryl (10 mg/kg, i.p., once a day for 7 days) ameliorated these reductions. No changes were found in [3H]CHA, [3H]MK-801, [3H]muscimol, [3H]PN200-110, [3H]cAMP, and [3H]IP3 binding. The results suggest that Naftidrofuryl may have beneficial effects on the age-related alterations in signal transmission and transduction systems in the brain. Because the acetylcholine system, adenylate cyclase, and PKC are considered to be involved in learning and memory processes, the result may have clinical implications. 相似文献
9.
Soonmyoung Paik M.D. 《Breast cancer research and treatment》1992,22(1):31-38
Summary Expression of IGF-I and IGF-II was studied in human breast cancer tissues by in situ hybridization. IGF-I mRNA was detected only in stromal cells adjacent to normal breast epithelial cells. Stromal cells associated with the tumor cells did not contain IGF-I, nor did malignant or benign breast epithelial cells. In contrast, IGF-II mRNA was found in both the malignant epithelial cells and their adjacent stromal cells. These data imply that stromal cells associated with breast epithelium may switch expression from IGF-I to IGF-II during breast cancer evolution. This appearance of IGF-II expression may identify cancer-associated stromal cells that have a fetal phenotype. 相似文献
10.
甲硫氨酸脑啡肽对抗体的产生和T细胞免疫功能具有调节作用。为了明确这种作用机制,本实验观察了抗体和白细胞介素-2(IL-2)的产生和基因表达。甲硫氨酸脑啡肽对3F3杂交瘤细胞的抗体产生及其轻链和重链基因表达影响不明显。较高浓度的甲硫氨酸脑啡肽(0.1nmol·L ̄(-1)-1μmol·L(-1))不仅促进IL-2的产生和IL-2mRNA的转录,而且能提高IL-2mRNA的稳定性。 相似文献