延髓中缝核5-羟色胺对清醒大鼠胃运动的影响

本工作采用应力传感器记录胃窦的运动,观察向清醒大鼠延髓中缝核注射1微升生理盐水中含6.25μg、12.5μg和25μg三种不同剂量的5-羟色胺(5HT)以及腹腔注射对氯苯丙氨酸(pCPA)或延髓中缝核注射5,6-双羟色胺(5,6DHT)以减少内源性5HT对胃运动的影响。实验结果表明:6.25μg 5HT有兴奋胃窦运动的趋势,12.5μg和25μg 5HT使胃窦收缩活动加强。将上述三种剂量的5HT注入外周静脉均不影响胃的运动。腹腔注射pCPA后第四天和延髓中缝核注射5,6DHT后第五天,抑制大鼠胃运动。此时,颈髓、延髓、中桥脑、间脑5HT含量均明显下降。提示延髓中缝核5HT参与胃运动的中枢性调节。     

下呼吸道的5-羟色胺免疫反应纤维

本文应用ABC免疫酶组织化学方法研究了5-羟色胺免疫反应纤维在豚鼠和大白鼠下呼吸道内的定位分布,结果发现反应纤维在两种动物的分布无明显差别,主要分布在:气管、支气管及肺内各级支气管粘膜上皮,平滑肌层,外膜疏松结缔组织,肺泡隔,肺内血管壁内及其周围。呼吸道粘膜的神经上皮体也呈5-羟色胺阳性反应。本文为进一步探讨5-羟色胺在呼吸系统的功能提供了形态学依据。     

大鼠腮腺的5-羟色胺免疫组织化学

目的：观察大鼠腮腺内5-HT的分布。方法：免疫组织化学ABC法。结果：大鼠腮腺各级导管的上皮细胞、毛细血管及小血管的内皮细胞均呈5-HT免疫反应阳性。免疫反应物分布于胞质，胞核为阴性反应。结论：大鼠腮腺各级导管上皮细胞内含有5-HT，其存在对腮腺的功能可能有一定调节作用。     

鱼藤酮致帕金森大鼠脑内5-羟色胺和5-羟色胺转运体的表达改变

目的 通过观察鱼藤酮处理大鼠脑内相关脑区5-羟色胺(5-HT)和5-羟色胺转运体(SERT)的表达变化,探讨鱼藤酮对5-HT能神经元的影响.方法 选用健康成年雄性Wistar大鼠42只,背部皮下注射鱼藤酮制作帕金森病大鼠动物模型,以免疫组织化学染色、免疫印迹法及流式细胞术显示大鼠脑内相关脑区5-HT和SERT的表达变化...     

不同生长期籽鹅消化道5-羟色胺的表达

目的:观察不同生长期籽鹅消化道内的5-羟色胺(5-HT)免疫活性细胞.方法:采用SP免疫组织化学方法,对不同生长期(1、 10、 30、 60、 90d)籽鹅消化道5-HT免疫活性细胞的分布密度与形态进行研究.结果:随着日龄的增长,籽鹅消化道5-HT细胞的数量逐渐增多.5-HT细胞在1日龄就已见于肠道各段,但分布数量较少,到90日龄达到高峰,在十二指肠和直肠分布密度最大,幽门部最少.结论:生长期籽鹅消化道5-HT细胞的分布、形态是与其功能相适应的.     

一氧化氮对体外培养的胚鼠脑干5-羟色胺能神经元生长发育的影响

研究体外培养条件下一氧化氮合酶(NOS)对胚鼠脑干5-羟色胺(5-HT)能神经元生长发育的影响,进一步探讨一氧化氮在胚脑发育过程中的作用。将孕14d SD胚鼠脑干细胞悬液接种于24孔培养板,实验分两组:即常规培养液组及NOS竞争性抑制剂L-NAME处理组。两组均在接种5、10、15、20d后终止培养,部分盖片行NADPH-d组织化学染色,余盖片行5-HT免疫组织化学染色。观察并计数各组NOS阳性神经元和5-HT样免疫阳性神经元的形态和数量。结果显示:经L-NAME处理的胚鼠脑干细胞在培养10d后出现NOS阳性神经元减少。虽在整个过程中未观察到5-HT样免疫阳性神经元胞体的变化,但其突起的密度及突起上膨体和生长锥的数量明显减少。以上结果表明:在生长发育的关键时期,应用NOS抑制剂会影响5-HT能神经元的形态发育和功能,提示NO参与调节神经元的发育与成熟过程。     

大鼠前庭神经核复合体内5-羟色胺1A受体的分布

为了研究5-羟色胺1A受体(5-HT1AR)亚型在大鼠前庭神经核复合体(VNC)内的分布情况,本文采用免疫组织化学方法,在光学显微镜下对5-HT1AR亚型免疫阳性结构进行了观察。结果显示:5-HT1AR免疫阳性产物在VNC各个核团全长均有分布,主要定位于VNC神经元的胞体和近侧端树突,呈弥散分布,但在胞浆中也观察到许多染色深浅不同、分布不均匀的点状阳性结构。其中5-HT1AR样阳性神经元在前庭内侧核的全长呈密集分布,在前庭下核的尾段呈中等密度分布,在前庭上核、前庭外侧核和X核的全长、前庭下核的吻段和中段以及Y核的中、尾段均呈低密度分布,Y核的吻侧呈稀疏分布。本文结果提示,5-HT1AR阳性结构广泛地分布于大鼠VNC内,它们可能在介导5-HT对神经元活动的调节,参与前庭信息的整合与加工方面发挥重要作用。     

多重脑震荡大鼠脑干中缝核团内5-羟色胺免疫阳性表达变化的研究

为了探讨多重脑震荡(multiple cerebral concussion,MCC)后大鼠中缝核团内5-羟色胺(5-HT)能神经元的变化规律,本实验采用自制单摆式机械打击装置复制MCC大鼠模型,研究伤后大鼠脑干中缝核团内5-HT及5-HT合成过程中的限速酶-色胺酸羟化酶(TPH)的表达。将56只大鼠随机分为7组:对照组、伤后1、2、4、8、16和24d组(n=8)。用免疫组织化学染色技术及图像分析法定量分析伤后大鼠脑干中缝核团内5-HT和TPH的表达变化。结果显示:(1)TPH免疫反应阳性产物在中缝背核、正中中缝核的表达在伤后2d时达到高峰,与正常对照组相比有显著性差异(P<0.05);中缝大核和中缝苍白核分别以伤后1d组和4d组阳性反应最强;(2)5-HT免疫反应阳性产物在中缝背核、正中中缝核的表达也在伤后2d时达到高峰,16、24d组基本恢复至正常水平;而中缝大核和中缝苍白核内5-HT的免疫反应性在各损伤组与正常对照组之间均无显著性差异(P>0.05)。以上结果表明,多重脑震荡后中缝核团内TPH和5-HT的表达增高,这为研究5-HT对MCC后认知障碍的影响提供了形态学依据。     

促性腺激素释放激素类似物对大鼠胃肠道5-羟色胺分泌的影响

目的 研究GnRH对胃肠道内5-HT分泌的影响。方法胃腔直接注射GnRH类似物阿拉瑞林(A1arelin GnRH—A)以模拟外分泌产生的GnRH，并以免疫组织化学、高压液相色谱电化学检测(HPLC-ECD)的方法对阿拉瑞林刺激后胃及十二指肠内5-HT免疫反应细胞、血清中5-HT含量进行检测。结果 胃腔内注射GnRH—A后，大鼠胃及十二指肠内5-HT免疫反应阳性细胞密度显著增多，但血清中5-HT含量显著减少。结论 外分泌的OnRH对于5-HT的释放起明显抑制作用，但对5-HT的合成可能不产生影响。     

大鼠伏核内5-羟色胺样和甲硫氨酸-脑啡肽样免疫反应阳性结构的观察

本文借助免疫组织化学技术,在光镜和电镜水平观察了大鼠伏核内5-羟色胺(5-HT)样和甲硫氨酸-脑啡肽(Met-ENK)样免疫反应阳性结构的分布。光镜观察:5-HT样免疫反应阳性的纤维和终末可见于伏核不同平面的各亚区,但内侧区和腹侧区的明显地多于背侧区和外侧区,尾段的阳性纤维多于吻段。根据伏核内5-HT样纤维的直径、行径和膨体的数量,可将其分为粗纤维、中等粗细纤维和细纤维3种,此3种纤维的区分以内侧区和腹侧区较明显。未见5-HT样阳性胞体。Met-ENK样免疫反应阳性的胞体仅见于腹侧区和内侧区腹侧部,少量散在分布。Met-ENK样阳性纤维和终末也主要分布于内侧区和腹侧区,外侧区和背侧区较少。Met-ENK样阳性纤维均属细纤维,行径弯曲,外观呈绒毛状。Met-ENK样阳性胞体、纤维和终末在吻尾方向上的分布无明显差异。电镜观察:5-HT样阳性轴突终末与阴性树突形成对称和非对称型轴树突触;Met-ENK样阳性树突与阴性轴突终末形成对称和非对称型轴-树突触。上述突触多见于内侧区和腹侧区。     

Neuronal responses to 5-hydroxytryptamine in the red nucleus of rats

The effects of microiontophoretic 5-hydroxytryptamine (5-HT) on the firing rate of red nucleus (RN) neurons were studied in urethane-anesthetized rats. The background discharge rate of almost all the neurons tested (97%) was modified by 5-HT, and generally increased (89%). Responses were dose dependent. Twenty-three percent of the excitatory responses were preceded by a short inhibitory phase. No significant difference in the effect of 5-HT was found between those RN neurons that project to the spinal cord and those that do not. The excitatory responses to 5-HT were blocked or greatly reduced by the 5-HT antagonists methysergide and ketanserin, and were even reversed in some cases. The 5-HT₂/5-HT_1A antagonist spiperone, in small doses, also blocked the transient inhibitory phases in addition to the excitatory effects. In RN neurons exhibiting a short-lasting inhibition in the response to 5-HT, the 5-HT_1A agonist 8-hydroxy-2(di-n-propyl-amino)tetralin (8-OH-DPAT) induced inhibitory effects. These results support the hypothesis that 5-HT exerts control throughout the RN, mostly by acting on 5-HT₂ receptors. Furthermore, an influence of this amine on the electrical activity of small groups of RN neurons by 5-HT_1A receptors, and eventually by different mechanisms, appears probable. The functional significance of serotoninergic control of RN neuronal activity is discussed.     

胎儿宫内生长迟缓脐血5—羟色胺变化及临床意义

目的：探讨胎儿宫内生长迟缓（ＩＵＧＲ）与５－羟色胺含量关系,方法：采用ＲＦ－５０００型荧光分光乐度计测量法测量正常体重组与ＩＵＧＲ组脐静脉、脐动脉血浆中５０ＨＴ含量。结果：正常新生儿体重及ＩＵＧＲ,脉静脉、脐动脉之间血浆中５－ＨＴ含量无明显差异（Ｐ〉０．０５）ＩＵＧＲ组脐静脉、脐动脉血浆中５－ＨＴ含量明显高于正常体重组,而且差异非常显著（Ｐ〈０．０１）,结论：ＩＵＧＲ脐血管痉挛与５－ＨＴ含量有密切     

Excitation and inhibition of rat medial vestibular nucleus neurones by 5-hydroxytryptamine

The effects of 5-hydroxytryptamine (5-HT) and related compounds on the discharge rate of tonically active medial vestibular nucleus (MVN) neurones were studied in an in vitro slice preparation of the dorsal brainstem of the rat. The majority (87 of 107, 82%) of MVN neurones were excited by 5-HT. Nine cells (8%) showed a biphasic response to 5-HT, which consisted of a brief inhibition followed by excitation. Eleven cells (10%) were inhibited by 5-HT. The excitatory effects of 5-HT were mimicked by alpha-methyl-5-HT and antagonised by ketanserin and ritanserin, indicating the involvement of the 5-HT₂ subtype of 5-HT receptor. In biphasic cells, blockade of 5-HT₂ receptors by ketanserin reduced the excitatory component of the response and revealed an enhanced initial inhibition. The inhibitory effects in biphasic cells, and in cells that showed a pure inhibition in response to 5-HT, were blocked by pindobind-5-HT and mimicked by 8-hydroxy-2-(di-n-propylamino)-tetralin indicating the involvement of 5-HT1A receptors. The significance of these findings in relation to the effects of 5-HT on vestibular reflex function is discussed.     

Facilitation by 5-hydroxytryptamine of ATP-activated current in rat pheochromocytoma cells

The effects of 5-hydroxytryptamine (5-HT) on an inward current activated by extracellular ATP were investigated in rat pheochromocytoma PC12 cells. Under whole-cell voltage-clamp conditions 5-HT (10 M) reversibly enhanced the amplitude of the current activated by 30 M ATP. The enhancement may not be due to an increase in the number of functional channels because the current activated by 300 M ATP was not remarkably augmented compared with the current activated by 30 M ATP. The current enhancement by 100 M 5-HT was less obvious than that by 10 M 5-HT. When the current kinetics were compared, activation of the ATP-evoked current was accelerated to the same extent by either 10 or 100 M 5-HT, whereas deactivation was largely more accelerated by 100 M 5-HT. Propranolol (10 M), a 5-HT₁ receptor antagonist, or LY53857 (10 M), a 5-HT₂ receptor antagonist, exerted an agonistic effect: the ATP-activated current was facilitated by these compounds. Metoclopramide (10 M), a 5-HT₃ receptor antagonist, neither facilitated the ATP-activated current, nor blocked the current facilitation by 5-HT. Guanosine 5-O-(2-thiodiphosphate) (GDP[S]) (2 mM), the non-hydrolysable analog of guanosine 5-triphosphate (GTP), or K-252a (2 M), a protein kinase inhibitor, did not affect the facilitation by 5-HT of the ATP-activated current when they were included in the intracellular solution. The ATP-activated current pre-facilitated by 10 M dopamine was not enhanced by 10 M 5-HT. Similarly, the pre-facilitation by 5-HT attenuated the current enhancement by dopamine. The results suggest that 5-HT facilitates the ATP-activated channels through receptors that are not readily classified into conventional subclasses of 5-HT receptors. The reciprocal masking between the current facilitation by 5-HT and that by dopamine, combined with their sensitivities to the compounds involved in the intracellular solution, indicates that the facilitation by 5-HT may share not all, but some, common cellular mechanism with that by dopamine.     

Treatment of acute gouty arthritis with the 5-hydroxytryptamine antagonist ondansetron

We report on a 28-year-old man with hematemesis, renal dysfunction, and arterial hypertension who suffered from an acute gouty attack presenting as podagra. Because of the accompanying symptoms conventional treatment of the gouty attack with colchicine or nonsteroidal anti-inflammatory drugs was contraindicated. We treated the pain of acute arthritis with the specific 5-hydroxytryptamine subtype 3 receptor antagonist ondansetron. Within 30 min after intravenous injection of this drug a substantial degree of pain relief had occurred. Unwanted side effects due to treatment were not observed. It is suggested that the 5-hydroxytryptamine released during a gouty attack induces pain via activation of 5-hydroxytryptamine subtype 3 receptors on nociceptive afferent nerve fibers. 5-Hydroxytryptamine subtype 3 receptor antagonists may therefore be a novel class of drugs for the effective treatment of acute gouty attacks when conventional treatment is contraindicated.Abbreviation 5-HT 5-hydroxytryptamine Correspondence to: H. Schworer     

The effect of some putative neurotransmitters on the release of 5-hydroxytryptamine and gamma-aminobutyric acid from slices of the rat midbrain raphe area.

The effect of various putative transmitters has been studied on the efflux of [³H]5-hydroxytryptamine and [³H]γ-aminobutyric acid from small superfused slices of the midbrain raphe area of the rat. The slices apparently contained functionally intact terminals for these transmitters since a depolarizing stimulus (50 mM KCl) stimulated the rate of efflux of [³H]5-hydroxytryptamine and [³H]γ-aminobutyric acid in a calcium-dependent fashion. Furthermore, slices accumulated radioactivity with apparent high affinity mechanisms. γ-Aminobutyric acid (50 and 100 μ m) and substance P (100 and 500μ m) stimulated the efflux of [³H]5-hydroxytryptamine. The effect of γ-aminobutyrate was blocked by picrotoxin (50 μ m) but not by strychnine (1 μ m). Other inhibitory amino acids (β-alanine, taurine and glycine) were without effect on the release of [³H]5-hydroxytryptamine. l-Noradrenaline (0.2–1 mM) stimulated the efflux of [³H]γ-aminobutyric acid but not that of [3H]5-hydroxytryptamine. Phentolamine (10μ m) but not (±)-propranolol (10 μ m) abolished the effect of 1 mM noradrenaline. Neither dopamine nor 5-hydroxytryptamine influenced the efflux of [3H]γ-aminobutyric acid.It is possible that interactions in the midbrain raphe area proposed from other studies can be mediated through presynaptic influences on transmitter release.     

5-Hydroxytryptophan reversal of reserpine enhancement of audiogenic seizure susceptibility in mice

Increased sensitivity to audiogenic seizures by reserpine was antagonized by 5-hydroxytryptophan (5HTP). The antagonism was dependent upon the conversion of 5HTP to 5 hydroxytryptamine (5HT) in brain since blockade of both cerebral and extracerebral decarboxylase prevented the 5HTP effect, whereas selective blockade of extracerebral decarboxylase did not affect the 5HTP antagonism. Increased seizure susceptibility occurred when brain concentrations of 5HT were decreased, while decreased susceptibility occurred when brain concentrations of 5HT were elevated. 5HTP did not alter norepinephrine or dopamine concentrations in brain. The results of this study indicate that 5HT plays a role in modulating audiogenic seizure susceptibility.     

Day-night differences in estimated rates of 5-hydroxytryptamine turnover in the rat pineal gland

Summary Rates of 5-hydroxytryptamine synthesis in various brain tissues can be estimated from the linear increase in 5-hydroxytryptophan levels following inhibition of 5-hydroxytryptophan decarboxylation with RO4-4602 or NSD-1015. In addition, NSD-1015 can prevent 5-hydroxytryptamine oxidative-deamination via monoamine oxidase inhibition, leading to linear decreases in a major metabolite of this amine, 5-hydroxyindole acetic acid. In the rat pineal gland we demonstrated similar increases in 5-hydroxytryptophan levels after nocturnal or diurnal injection of RO4-4602 (100 mg · kg^–1) or NSD-1015 (200 mg · kg^–1). Similar decreases in 5-hydroxyindole acetic acid were also observed after nocturnal or diurnal injection of NSD-1015 or pargyline (an inhibitor of monoamine oxidase) (75 mg · kg^–1). 5-Hydroxytryptamine levels increased after nocturnal pargyline injection but remained constant after diurnal pargyline administration. 5-Hydroxytryptamine levels exhibited little change following nocturnal injection of NSD-1015 but decreased linearly after diurnal injection of NSD-1015. We suggest that (1) rat pineal 5-hydroxytryptamine synthesis is increased nocturnally, (2) metabolic utilization, primarily by oxidative-deamination, of 5-hydroxytryptamine is increased diurnally and (3) basal levels of pineal 5-hydroxytryptamine may be stored within adrenergic nerve endings which innervate the pinealocytes responsible for synthesizing this amine, thus protecting or otherwise making unavailable this pool of 5-hydroxytryptamine for metabolic utilization.     

Release of endogenous 5-hydroxytryptamine from resting and stimulated enteric neurons

Physiological and biochemical evidence has indicated that there may be serotoninergic neurons in the enteric nervous system. A critical step in the identification of a neurotransmitter is the demonstration of the release of the substance upon nerve stimulation. We now report the release of endogenous 5-hydroxytryptamine from enteric neurons. Segments of guinea-pig small intestine were everted and perfused in vitro through the newly created serosal lumen. Tests with [³H]5-hydroxytryptamine revealed the existence of a tissue barrier preventing diffusion of mucosal (enteroendocrine cell) 5-hydroxytryptamine into the perfusate; thus, all 5-hydroxytryptamine in the perfusate was of neural origin. The gut was stimulated electrically. 5-Hydroxytryptamine in the perfusate and in the myenteric plexus was assayed by a specific radioenzymatic method. 5-Hydroxytryptamine was present in the myenteric plexus; it was released into the perfusate spontaneously and the release was enhanced by electrical stimulation. The stimulated, but not the spontaneous, release of the amine was Ca²⁺-dependent. Comparison with the release of newly taken up [³H]5-hydroxytryptamine showed that the specific radioactivity of electrically released 5-hydroxytryptamine was higher than that of either the spontaneously released or tissue amine. Stimulation also increased the release of 5-hydroxytryptamine more than that of its metabolites in the perfusate.These results indicate that 5-hydroxytryptamine is an endogeneous constituent of the enteric nervous system, that it is released by electrical field stimulation of enteric nerves, and that newly taken up 5-hydroxytryptamine is released preferentially by these neurons.     

The spontaneous release of 5-hydroxytryptamine and acetylcholine within the diencephalon of the unanaesthetized rhesus monkey

Summary The diencephalon of the unanaesthetized rhesus monkey was explored for sites which release either 5-hydroxytryptamine (5-HT) or acetylcholine (ACh), or both, spontaneously. In 34 monkeys push-pull perfusion cannulae were implanted so that the tips rested in 66 different loci of the hypothalamus and thalamus. Each site was perfused for 30 min at 24–48 h intervals, and usually three perfusions were carried out for the 5-HT assays and three for ACh assays.Within 45 distinct loci of the hypothalamus, four types of sites were identified at which only 5-HT was released, only ACh was released, both 5-HT and ACh were released, or neither substance was detected. Within 21 sites representing three of the major masses of thalamic nuclei (lateral, medial and posterior), the same kinds of sites were found. In the hypothalamic sites, 5-HT output varied between 0.1–2.0 ng per 30 min perfusion interval, whereas ACh varied between 0.2–3.0 ng per 30 min. In thalamic loci, 5-HT release ranged between 0.5–3.0 ng per 30 min and ACh between 0.1–10.0 ng per 30 min. The sites which released 5-HT and ACh were scattered widely and unevenly throughout these diencephalic structures. However, there was a greater release of 5-HT in the anterior and in the posterior hypothalamus, and more ACh in the thalamus than in the hypothalamus.Visiting Associate Professor from the Institute of Pharmacology, Medical Faculty, University of Belgrade, Yugoslavia. Supported by NTH Health Sciences Advancement Award, PHS 5-S04 Pr-0615.