Elevated concentration of 5–hydroxytryptamine in ultrafiltrate of human liver vein plasma after infusion of amino acids

Intragastric infusion of amino acids causes the release from the liver of a factor with stimulatory effect on smooth muscle. The effect of liver vein plasma ultrafiltrate was tested on isolated preparations of rat fundus. The ultrafiltrates collected after amino acid infusion had a 3–5 times higher stimulatory effect on smooth muscle contraction than those collected from control plasma. The active principle was isolated, purified by different chromatographic procedures and identified as 5–hydroxytryptamine (serotonin). No other compound with contractile effect on smooth muscle was detected.     

氧化低密度脂蛋白、低氧和5-HT对血管平滑肌细胞5-HT2A受体及胞内游离钙的影响

目的　为探讨粥样硬化病变动脉对 5 - HT收缩反应增加的机制 ,观察与粥样硬化有关因子氧化低密度脂蛋白 (ox L DL)、低氧、5 - HT对血管平滑肌细胞 5 - HT2 A受体及其基因表达 ,以及细胞 [Ca2 ]i的效应。方法　分别将大鼠主动脉平滑肌细胞单独以 5 0 μg/ m l ox L DL 培养 8h,2 %低氧处理 2 4和 48h,10 μm ol/ L 5 - HT处理30 min,放射配基结合分析测定 5 - HT2 A受体 ;RT- PCR和 Southern杂交检测受体基因的 m RNA;激光共聚焦扫描显微镜测单个细胞 [Ca2 ]i。结果　经 ox L DL、低氧、 5 - HT处理 ,血管平滑肌细胞 5 - HT2 A受体显著上调 (P<0 .0 1) ;ox L DL及低氧处理的受体基因的 m RNA表达增加 ;ox L DL、低氧处理后 ,5 - HT刺激的血管平滑肌细胞[Ca2 ]i升高幅度显著加大 (P<0 .0 5及 P<0 .0 1)。结论　 ox L DL、低氧、5 - HT引起血管平滑肌细胞 5 - HT2 A受体上调及细胞 [Ca2 ]i增加 ,可能是粥样硬化动脉对 5 - HT收缩反应增强的部分原因。     

Serotonin transporter polymorphism modifies the association between depressive symptoms and sleep onset latency complaint in elderly people: results from the ‘InveCe.Ab’ study

Previous studies have documented the involvement of the central nervous system serotonin in promoting wakefulness. There are few and conflicting results over whether there is an actual association between bearing the short allele of serotonin transporter promoter polymorphism (5‐HTTLPR) and worse sleep quality. This study examined whether sleep onset latency complaint is associated with the 5‐HTTLPR triallelic polymorphism in the SLC6A4 gene promoter and whether this polymorphism influences the relationship between sleep onset latency complaint and depressive symptoms in elderly people. A total of 1321 community‐dwelling individuals aged 70–74 years were interviewed for sleep onset latency complaint and for sleep medication consumption. Participants’ genomic DNA was typed for 5‐HTTLPR and rs25531 polymorphisms. Depressive symptoms were evaluated with the Geriatric Depression Scale Short form and general medical comorbidity was assessed by the Cumulative Illness Rating Scale. The presence of a past history of depression was recorded. The S′ allele of the 5‐HTTLPR triallelic polymorphism was associated with sleep onset latency complaint. This association was maintained after adjusting for depressive symptoms, sex, age, history of depression and medical comorbidity. After stratification for 5‐HTTLPR/rs25531, only in S′S′ individuals high depressive symptoms were actually associated with sleep onset latency complaint. These data indicate that the low‐expressing 5‐HTTLPR triallelic polymorphism is an independent risk factor for sleep onset latency disturbance. Furthermore, the 5‐HTTLPR genotype influences the association between depressive symptoms and sleep onset latency complaint.     

5-Hydroxytryptamine2A receptor binding activity of compounds from Litsea sessilis

A 96-well microplate filtration based 5-HT(2A) receptor-radioligand binding assay was optimized and adopted to carry out a bioassay-guided fractionation of the methanol extract of the leaves of Litsea sessilis. This purification led to the isolation of two compounds identified as (+)-boldine (1) and (+)-dehydrovomifoliol (2). (+)-Boldine binds to 5-HT(2A) receptors at high concentrations with a K(i) value of 2.16 microm. However, (+)-dehydrovomifoliol showed minimal competitive inhibition on the binding of [(3)H]ketanserin to the same receptor with a K(i) value of 2.06 mm. These results suggest that (+)-boldine influences the activity of 5-HT(2A) receptors through competitive binding as an agonist or antagonist.     

Ultrastructural localization of serotonin 2A and N-methyl-D-aspartate receptors in somata and dendrites of single neurons within rat dorsal motor nucleus of the vagus

Both glutamate and serotonin are potent modulators of autonomic functions involving the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMNV) at the level of the area postrema. Moreover, many of the dendrites in this NTS region express both N-methyl-D-aspartate (NMDA) and serotonin (5HT) 2A receptors, and some of these dendrites may arise from the adjacent DMNV. Thus, single neurons in DMNV may also express both receptors. To test this hypothesis, we used electron microscopic immunocytochemistry for dual localization of the essential R1 subunit of the NMDA receptor (NR1) and the 5HT2A receptor in rat intermediate DMNV, a region serving mainly gastrointestinal functions. Gold particles representing NR1 and peroxidase reaction product for 5HT2A receptors were seen in the cytoplasm, as well as on distinct segments of the plasma membrane of many dendrites. Of the NR1-labeled dendrites, 31% (254/814) also contained 5HT2A immunoreactivity; among the 5HT2A-labeled dendrites, 52% (254/485) expressed NR1. The 5HT2A labeling was also present in numerous small unmyelinated axons, axon terminals, and glial processes. These profiles were largely without NR1 immunoreactivity, although NR1 was detected in some of the dendrites postsynaptic to 5HT2A-labeled terminals. Our results suggest that calcium entry through NMDA channels and 5HT2A receptor activation may dramatically affect postsynaptic excitability of single neurons in the DMNV. In addition, the findings also indicate that the 5HT2A receptor is strategically positioned for involvement in modulation of the presynaptic release of neurotransmitters affecting the postsynaptic activity of DMNV neurons responsive to NMDA activation.     

Effects of the 5-HT3 antagonist cilansetron vs placebo on phasic sigmoid colonic motility in healthy man: a double-blind crossover trial

AIMS: 5-hydroxytryptamine3 receptor antagonists act antiemetically and slow colonic transit. This study evaluated effects of the high-affinity 5-HT3 antagonist, cilansetron, on fasting, meal-and anticholinesterase-stimulated phasic contractile activity of the human sigmoid colon as well as on bowel habits and stool consistency. METHODS: Five female and seven male healthy volunteers received, during three 7 day periods separated by 7 day wash-out periods, 4 mg cilansetron, 8 mg cilansetron or placebo three times daily orally under random, double-blind, crossover conditions. On day 8 of each treatment period, motility 20-40 cm from the anal verge was recorded using five pressure sensors spaced at 5 cm intervals. After a basal 30 min, subjects swallowed a further dose of the scheduled treatment; 60 min later, blood was taken for the determination of plasma cilansetron levels. Thereafter, subjects ingested a 4200 kJ meal and 250 ml sweetened mallow tea (166 kJ); 90 min after meal onset, 1 mg neostigmine was administered intramuscularly and motility recording was continued for 60 min RESULTS: Phasic contractile activity and intraluminal base-line pressure increased postprandially and more so after neostigmine. With cilansetron, the area under the pressure curve as the primary outcome variable and the number of contractions were significantly greater than with placebo (P = 0.005), amplitude and duration of contractions and base-line pressure were not affected. The effects of the two cilansetron dosages did not differ. With cilansetron, stool tended to become firmer. No adverse effects were observed. Plasma levels were highest with 8 mg cilansetron. CONCLUSIONS: Cilansetron slightly augments meal-stimulated and markedly neostigmine-stimulated phasic motility of the sigmoid colon. When administered over 7 days, it tends to increase stool consistency and is well tolerated.     

大鼠损伤皮肤组织5-羟色胺含量测定

为寻找生前损伤早期诊断指标，采用免疫散射浊度分析法，对生前、死后不同时间形成的大鼠切创皮肤的５ＨＴ进行对比分析。结果显示：生前损伤５分钟，５ＨＴ含量明显升高，１５分钟达高峰，６０分钟开始下降。生前损伤各组５ＨＴ含量均较自身对照组明显升高（升高４０％以上，Ｐ＜００５）；而死后５分钟和１５分钟组皮肤中５ＨＴ含量均较自身对照组升高（Ｐ＜００５），但增加幅度均低于３６％。提示，如创缘皮肤５ＨＴ含量比自身对照升高４０％，可判断为生前伤     

“气至病所”对相关皮瓣浸泡液内5-羟色胺、肾上腺素、去甲肾上腺素含量的影响

为研究“气至病所”的外周神经体液机制 ,本课题借用福尔马林试验 ,在大鼠一侧足底皮下注射 5%福尔马林 50 μL作为局部病灶 ,观察电针“阳陵泉”、“外丘”穴 (刺激参数为 1～ 3V ,4～1 6Hz,3 0min)对大鼠自发痛行为反应、相关皮瓣浸泡液内 5 羟色胺 ( 5 HT)、肾上腺素 (E)、去甲肾上腺素 (NE)含量的影响。结果表明 ,大鼠一侧足底注射福尔马林后 0～ 80min出现明显的自发痛行为反应 ,电针能显著减少大鼠福尔马林试验后的自发痛行为反应 ;大鼠一侧足底注射福尔马林后60min相关皮瓣浸泡液内 5 HT、NE、E含量显著增加 ,电针能拮抗大鼠福尔马林试验后相关皮瓣浸泡液内 5 HT、NE、E含量的上升。结果提示 ,循经电针可通过外周神经体液机制促使“气至病所” ,减少局部炎症介质的释放和交感传出导致的痛过敏反应     

5-羟色胺免疫电极的研制和应用

研制了电位型无标记５－羟色胺（５－ＨＴ）免疫电极。以偶联法制备抗体膜,结合抗原后的复合膜与空白膜的△Ｅ值与５－ＨＴ的浓度成线性关系。电极的线性范围为１．１８×１０－７～６．２７×１０－６ｍｏｌ／Ｌ,检测下限为１．１２×１０－７ｍｏｌ／Ｌ,斜率为－１３．０８ｍｌ,相关系数ｒ＝－０．９９８４,对血中其他物质选择性良好,抗体膜片一次性使用,以标准曲线法测定了牛血小板中５－ＨＴ浓度。