外周5-羟色胺在动脉粥样硬化中的作用研究进展

动脉粥样硬化(AS)是众多心血管疾病的病理基础,研究发现外周5-羟色胺(5-HT)与动脉粥样硬化关系密切.本文综述外周5-羟色胺在动脉粥样硬化发生发展过程中发挥的作用,包括促进巨噬细胞源性泡沫细胞形成,血管平滑肌细胞增殖和迁移,血管收缩,血小板聚集和血栓形成,并总结选择性5-羟色胺2A受体拮抗剂盐酸沙格雷酯在动脉粥样硬化治疗中的应用,以期为动脉粥样硬化研究提供新思路.     

肝脏5-羟色胺相关系统与肝脏疾病

本文综述了肝脏5-羟色胺相关系统与肝损伤、肝再生、非酒精性脂肪肝及非酒精性脂肪性肝炎的关系,展望了5-羟色胺受体、转运体等作为新型治疗肝脏疾病的作用靶点的潜力.     

肺动脉高压的药物治疗

肺动脉高压(PAH)是一种由异源性疾病和不同发病机制引起的以肺动脉压力增高为表现的疾病状态。PAH的传统治疗主要集中在支持治疗及非选择性血管扩张药等基础治疗。近年来,针对其发病机制各个环节的靶向治疗逐步开展,FDA已批准6种治疗PAH的药物,分别属于前列环素类似物、内皮素受体拮抗剂和磷酸二酯酶5抑制剂。5-羟色胺受体拮抗剂、Rho激酶抑制剂、PAR-2抑制剂正处于临床前研究阶段。     

5-羟色胺与创伤后应激障碍的研究进展

创伤后应激障碍(posttraumatic stress disorder,PTSD)是当机体遭受威胁生命或者强烈精神创伤后发生的疾病。近年来研究发现,5-羟色胺(5-HT)可能通过5-羟色胺转运体 (SERT)、5-HT受体(主要包括5-HT 1A 、5-HT1B、5-HT2A和5- HT2C受体),以及多巴胺、去甲肾上腺素等神经递质相互作用,参与PTSD的发生,该文就此进行综述。     

介导豚鼠腹腔神经节细胞5-羟色胺去极化反应的受体亚型

目的在豚鼠腹腔神经节(CG)细胞上鉴定介导5-羟色胺(5-HT)去极化反应的受体亚型。方法应用离体细胞内记录技术。结果赛庚啶(cyproheptad ine,5-HT1/2受体拮抗剂)和BRL 24924(5-HT1P受体拮抗剂)可逆地阻抑5-HT慢去极化反应,而sp iperone(5-HT1A受体拮抗剂),和m ian-serin(5-HT2受体拮抗剂),对5-HT慢去极化反应无明显影响;MDL 72222(5-HT3受体拮抗剂)对5-HT慢去极化反应无明显影响,却能够可逆地阻抑5-HT快去极化反应;压力注射MCPP(5-HT1P受体激动剂)可使5-HT敏感的CG神经元出现慢去极化反应且此反应能够被BRL 24924可逆地阻抑。结论豚鼠CG细胞的5-HT快、慢去极化反应分别由5-HT3和5-HT1P受体介导的。     

5-羟色胺综合征的临床特征、诊断及防治

5-羟色胺综合征是一种由治疗药物引起的可能危及生命的不良反应。发生机制为5-羟色胺(5-HT)在神经系统内积蓄,过度激活突触后5-HT受体,导致5-HT能神经系统活动增强,其临床特征为精神障碍、自主神经功能亢进及神经肌肉功能异常。本综合征常发生于抗抑郁药联用或与其他药物联用时,主要依据临床表现诊断。治疗包括停撤可疑药物、密切观察、控制激越行为、给予5-HT拮抗剂、对症治疗、并发症的处理等。本综合征重在预防。     

齐拉西酮与利培酮治疗精神分裂症对照研究

<正>齐拉西酮胶囊是一种非典型抗精神病药物,为5-羟色胺(5-HT2A)受体和多巴胺(D2)受体拮抗剂,为探讨国产齐拉西酮治疗精神分裂症的疗效和安全性,我们以利培酮片(商     

格拉司琼不同给药模式对曲马多镇痛病人胃肠动力的影响

盐酸格拉司琼是一种高效高选择性的5-羟色胺受体拮抗剂，它选择性地作用于5-羟色胺受体，从而有效控制和治疗恶心、呕吐。本研究拟对其对曲马多术后镇痛引起恶心、呕吐(PONV)的防治效果与氟哌利多进行比较，并观察其合理的给药模式。     

新作用机制肺动脉高压靶向治疗药物研究进展

肺动脉高压是一类以肺动脉渐进性闭塞导致肺血管阻力逐渐升高进而发生右心室衰竭的一种恶性肺血管疾病。随着肺动脉高压病理生理学和分子生物学等方面研究的发展,出现了许多新作用机制的肺动脉高压靶向治疗药物。本文根据国内外相关文献报道,本文将从鸟苷酸环化酶激活剂、线粒体调节剂、抗炎和免疫调节剂、酪氨酸激酶抑制剂、5-羟色胺受体拮抗剂、右心室靶向治疗药物等方面进行综述。     

欧盟评估抗抑郁药引起PPHN风险

欧洲药品管理局（EMA）人用药品委员会药物警戒工作组对5-羟色胺能抗抑郁药引起的新生儿持续性肺动脉高压（PPHN）风险进行了评估,并建议修订药品说明书。     

5-Hydroxytryptamine and platelets: uptake and aggregation in hypoxic pulmonary hypertensive rats

Pulmonary hypertension is associated with various alterations in 5-hydroxytryptamine (5-HT) physiology. In this study in platelets from hypoxic pulmonary hypertensive rats (10% O(2); 1 week) and normoxic rats (room air), (i) initial rates of specific [3H]5-HT uptake were measured and (ii) potentiation of collagen- and ADP-induced aggregation by 5-HT was quantified. The platelet count was almost halved in hypoxic rats. In uptake experiments, there was a decrease in 5-HT uptake in platelets from hypoxic compared with normoxic rats, due to a 36% reduction in the maximal initial rate of uptake. The aggregation experiments showed that 5-HT (1-100 microM) increased the magnitude of responses to collagen and the duration of responses to ADP, but there was no difference between hypoxic and normoxic rats. Abnormalities in platelet function may conceivably lead to increases in plasma 5-HT levels in hypoxic pulmonary hypertension, but are unlikely to aggravate pulmonary thromboembolism.     

The role of 5-HT on the cardiovascular and renal systems and the clinical potential of 5-HT modulation

The main peripheral sources of 5-hydroxytryptamine (5-HT) are as a neurotransmitter and local hormone in the gastrointestinal tract, and stored in circulating platelets and pulmonary neuroepithelial bodies. 5-HT has been shown to have many possible physiological and pathophysiological roles on the cardiovascular and renal systems. Thus, 5-HT may contribute to valvular heart disease, coronary artery disease, pulmonary hypertension, pulmonary embolism, pre-eclampsia, peripheral vascular disease and diabetic nephropathy. Consequently, modulators of the 5-HT system have diverse clinical potential. For instance, selective 5-HT subtype 3 receptor (5-HT₃) antagonists may have potential in the treatment of the pain associated with myocardial infarction. MCI-9042 (sarpogrelate) or other 5-HT_2A antagonists may have clinical potential for the treatment of vasospastic angina, ischaemic heart disease, reperfusion injury and hindlimb ischaemia. Several modulators of 5-HT (5-HT transporter inhibitors, 5-HT_1B and _2B antagonists) may have potential alone or in combination in the treatment of pulmonary hypertension. In hypertension, agonists at the 5-HT₇ and antagonists at the 5-HT_2B may reduce blood pressure, and in diabetes, sarpogrelate may protect against nephropathy.     

Alterations in pulmonary vascular function in rats exposed to intermittent hypoxia

Vasoactive agents were examined in arteries from control rats and rats exposed to intermittent hypoxia (10% oxygen; 8 h/day) for 3, 5 or 20 days. Hypoxic rats developed right ventricular hypertrophy after 5 days, but became pulmonary hypertensive (elevated right ventricular systolic pressure; RVSP) only after 20 days. In pulmonary arteries (main and intralobar), responses to acetylcholine and ionomycin (endothelium-dependent vasodilators) were reduced after 20 and 5 days of intermittent hypoxia, whereas contractions to 5-hydroxytryptamine (5-HT) were enhanced (potency increase >10-fold) after 20, 5 and 3 days. Contractions to endothelin-1 and a thromboxane-mimetic, but not Ca(2+), were also increased. No changes in vascular function occurred in aorta. Since changes in pulmonary vascular function preceded the increase in RVSP they do not result from, but may contribute to, the development of hypoxia-induced pulmonary hypertension. If similar changes occur in humans, they may be important in conditions characterised by intermittent, as opposed to continuous, hypoxia.     

间尼索地平对野百合碱诱导的肺动脉高压防治作用及其抗5-羟色胺—细胞外信号调节激酶通路的机制探讨

研究间尼索地平对野百合碱诱导的肺动脉高压的防治作用及其作用机制。大鼠单剂量皮下注射野百合碱(60 mg·kg^-1)制备肺动脉高压模型。导管法测定肺血流动力学指标；光镜观察肺小动脉结构的改变；同时测定血清中MDA及SOD的含量(活性)；免疫印迹法测定PCNA、ERK1和p-ERK的表达水平；免疫组化法观察5-HT和PCNA的表达。结果表明，与正常对照组相比，模型组大鼠的平均肺动脉压及右心指数明显增加；肺小动脉肌化程度加重；丙二醛含量显著升高，超氧化物歧化酶活性明显降低；PCNA和5-HT阳性细胞数目明显增加；PCNA蛋白表达及p-ERK/ERK1比率也显著增加，不同剂量间尼索地平在一定程度上逆转了上述变化。间尼索地平对野百合碱诱导的肺动脉高压表现出一定的保护作用。这一作用可能与其降低5-HT的表达，抑制ERK/MAPK信号通路有关。     

2,6-二甲基-4-(2-氯苯基)-1,4-二氢-3,5-吡啶二羧酸二甲酯的抗5-羟色胺作用在防治野百合碱性大鼠肺动脉高压中的意义

采用免疫组化,图像分析,细胞培养和细胞内游离钙离子浓度(［Ca²⁺］_i)测定等方法研究2,6- 二甲基-4-(2-氯苯基)-1,4-二氢-3,5-吡啶二羧酸二甲酯（DCDDP）防治野百合碱（MCT）所致肺动脉高压的作用机理. 结果发现每天ip DCDDP 5-500 μg ·kg^-1 1次, 连续28 d, 能够明显地减少MCT(60 mg·kg^-1 sc)引起的大鼠肺组织中5-HT相对含量及其受体阳性细胞数目增多,对5-HT引起的肺动脉平滑肌细胞增生,收缩及其［Ca²⁺］_i增高都有显著的抑制作用. 结果提示,抑制肺组织中5-HT含量及其受体数目的增加, 对抗5-HT引起的血管平滑肌细胞增生及收缩, 可能是DCDDP防治MCT性肺动脉高压的重要机理之一.     

The role of 5-HT on the cardiovascular and renal systems and the clinical potential of 5-HT modulation

The main peripheral sources of 5-hydroxytryptamine (5-HT) are as a neurotransmitter and local hormone in the gastrointestinal tract, and stored in circulating platelets and pulmonary neuroepithelial bodies. 5-HT has been shown to have many possible physiological and pathophysiological roles on the cardiovascular and renal systems. Thus, 5-HT may contribute to valvular heart disease, coronary artery disease, pulmonary hypertension, pulmonary embolism, pre-eclampsia, peripheral vascular disease and diabetic nephropathy. Consequently, modulators of the 5-HT system have diverse clinical potential. For instance, selective 5-HT subtype 3 receptor (5-HT(3)) antagonists may have potential in the treatment of the pain associated with myocardial infarction. MCI-9042 (sarpogrelate) or other 5-HT(2A) antagonists may have clinical potential for the treatment of vasospastic angina, ischaemic heart disease, reperfusion injury and hindlimb ischaemia. Several modulators of 5-HT (5-HT transporter inhibitors, 5-HT(1B) and (2B) antagonists) may have potential alone or in combination in the treatment of pulmonary hypertension. In hypertension, agonists at the 5-HT(7) and antagonists at the 5-HT(2B) may reduce blood pressure, and in diabetes, sarpogrelate may protect against nephropathy.     

野百合碱诱导的肺动脉高压大鼠肺血管5-HT转载体表达增强

目的　研究野百合碱诱导的大鼠肺动脉高压与5 HT转载体基因表达的关系。方法　应用MCT诱导的慢性肺动脉高压大鼠模型,建立离体动脉环5 HT浓度反应曲线;HE染色观察肺动脉构型重建,应用RT PCR检测大鼠肺动脉5 HT转载体mRNA表达。结果　MCT大鼠肺血管对5 HT收缩反应增强,肺肌型小动脉中膜增厚,MCT诱导的肺动脉高压大鼠肺血管5 HT转载体mRNA表达明显增多。5 HT转载体基因表达与肺肌型小动脉中膜增厚有明显相关性。结论　MCT诱导的肺动脉高压大鼠肺血管构型重建及5 HT引起收缩反应增强,伴有5 HT转载体mRNA表达增多;同时5 HT转载体mRNA表达与肺肌型小动脉中膜增厚有明显相关性,提示5 HT转载体可能在肺动脉高压中起重要作用。     

A comparison of the locomotor effects of 5-hydroxytryptamine and 5-hydroxytryptophan administered via two systemic routes

This study compared the effects of systemically administered 5-hydroxytryptamine (5-HT) and 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP) on tilt cage locomotor activity in rats. 5-HT was a more potent inhibitor of activity than 5-HTP via both the s.c. and i.p. routes. The effect of 5-HT itself was greater when administered i.p., whereas the effects of 5-HTP were independent of the route of administration. These results indicate that behavioral changesfollowing 5-HTP injection may be attributable to the peripheral effects of 5-HT.     

Hyperoxia alters platelet disposition of serotonin

Exposure of mice to normobaric 100% oxygen for 24-96 h is known to damage the pulmonary capillary endothelium and alter the disposition of serotonin (5-hydroxytryptamine, 5-HT). We now report that such exposure increased the concentration of platelets and decreased the platelet content of 5-HT and a tracer dose of [3H]5-HT. After 48 h of hyperoxia exposure, the platelet concentration was elevated to 121% of air-exposed control values and the content of 5-HT and [3H]5-HT/10(9) platelets was decreased 76% and 57%, respectively. Kinetic analysis of the platelet 5-HT uptake process indicated that hyperoxia exposure caused an increased affinity and decreased velocity of transport. After 48 h of oxygen exposure the Km for platelet 5-HT uptake was 1.91 +/- 0.67 X 10(-7) M and the Vmax 30.1 +/- 4.6 pmol/10(8) platelets/4 min compared to air-exposed control values of Km 3.37 +/- 0.32 X 10(-7) M and Vmax 46.7 +/- 3.5 pmol/10(8) platelets/4 min, respectively. These changes in platelet 5-HT uptake and disposition may contribute to the pathophysiology of the pulmonary microvascular response to hyperoxia-induced injury.     

The action of methylated derivatives of 5-hydroxytryptamine at ganglionic receptors

Changes in resting membrane potential induced by 5-HT, methylated derivatives of 5-HT and DMPP were recorded from the rabbit isolated superior cervical ganglion by the sucrose-gap method. Responses were evoked by injections into the superfusion stream to the ganglion of 0.01–0.2 μmol. Whereas 5-HT and DMPP evoked a relatively brief depolarization followed by an after-hyperpolarization, N,N-dimethyl 5-HT (DM5-HT) and N,N,N-trimethyl 5-HT (TM5-HT) evoked depolarizations of long duration. 5-Hydroxytryptamine and DMPP were approximately equipotent; DM5-HT was 8 times and TM5-HT 70 times more active than 5-HT.Quipazine was a selective antagonist of responses to 5-HT and hexamethonium a selective antagonist of responses to DMPP. Quipazine (1 μM) reduced in amplitude responses to 5-HT by 94%, those to DM5-HT by 37%, and those to TM5-HT by 10%; responses to DMPP increased in amplitude by 42%. When superfused over the ganglion 5-HT (10 μM) reduced responses to 5-HT by 56%, those to DM5-HT by 27%, those to TM5-HT by 25%, and those to DMPP by 9%. Hexamethonium (100 μM) reduced responses to DMPP by 84%, those to DM5-HT by 64% and those to TM5-HT by 86%; there was no reduction of responses to 5-HT which were potentiated in 7 of 13 experiments. Thus, during nicotinic receptor blockade responses to 5-HT were often enhanced, while in the presence of quipazine responses to DMPP were often enhanced.A dual action of DM5-HT and TM5-HT at ganglionic nicotinic and 5-HT receptors is likely. Potentiation of responses mediated via one species of receptor during blockade of the other suggests that 5-HT and nicotinic receptors may be in close association in the membrane.