Effect of beta-endorphin imprinting during late pregnancy on the brain serotonin and plasma nocistatin levels of adult male rats.

Female rats were treated with 10 microg of beta-endorphin on the 19th day of pregnancy. Offspring were studied when five months old. Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content in four brain regions were determined by HPLC-EC and the nocistatin levels of blood plasma using RIA methods. In each brain region studied, the 5-HT levels were highly significantly reduced and that of 5-HIAA in three regions was highly significantly increased. When 5HIAA/5HT ratios, as a measure of serotonin turnover, were calculated, imprinted animals showed extremely high values. Plasma nocistatin level was also significantly elevated. The results call attention to the effect of perinatal endorphin imprinting and its long-term consequences (e.g., setting of aggressiveness, pain tolerance).     

蓝斑在刺激视上核镇痛中的作用

应用核团微量注射、放射免疫测定（ＲＩＡ）和高压液相（ＨＰＬＣ）观察了刺激视上核（ＳＯＮ）对蓝斑（ＬＣ）灌流液中催产素（ＯＴ）、精氨酸加压素（ＡＶＰ）、去甲明上素（ＮＥ）和５－羟色胺（５－ＨＴ）的含量的变化以及斑注射Ｏ笔ＡＶＰ的拮抗剂对痛阈（ＰＴ）的影响。结果表明;刺激ＳＯＮ后３０到９０ｍｉｎ,ＬＣ灌流液中ＯＴ的含量,３０ｍｉｎＡＶＰ的含量,６０ｍｉｎ５－ＨＴ的含量明显增加,而ＮＥ的含量在３０和６０     

Serotonin Regulation of Serotonin Uptake in RN46A Cells

1. Aim: The role of the serotonin transporter (SERT) is to remove serotonin (5-HT) from the synaptic space. In vitro studies have shown that 5-HT uptake via SERT is influenced by the availability of its substrate, 5-HT. We used RN46A cells, a line that expresses SERT, to investigate 5-HT regulation of 5-HT uptake and the intracellular signaling pathways involved. RN46A cells also express mRNAs for 5-HT receptors (5-HT_1A, 5-HT_1B, 5-HT_2A, and 5-HT_2C) and as cAMP and intracellular Ca²⁺ are modulated by different 5-HT receptors, we studied both pathways.2. Methods: 5-HT uptake was determined as imipramine-inhibitable uptake of [³H]5-HT, intracellular cAMP was measured by RIA and intracellular Ca²⁺ changes were determined using the ratiometric method of intracellular Ca²⁺ imaging.3. Results: For uptake experiments, cells were kept for 30 min either with or without 1 μM 5-HT in the medium before measuring uptake. Removal of 5-HT for 30 min significantly decreased [³H]5-HT uptake. The absence of 5-HT for 15 min failed to induce any changes in intracellular cAMP levels. Removal of 5-HT from the medium did not change intracellular Ca²⁺ levels either; however, adding 1 μM 5-HT after 5 min in 5-HT-free conditions rapidly increased intracellular Ca²⁺ levels in 50% of the cells. The remaining cells showed no changes in the intracellular Ca²⁺ levels.4. Conclusions: We have shown that in RN46A cells, that endogenously express SERT and mRNAs for several 5-HT receptors, changes in 5-HT levels influence 5-HT uptake rate as well as induce changes in intracellular Ca²⁺ levels. This suggests that 5-HT may utilize intracellular Ca²⁺ to regulate 5-HT uptake.     

Molecular mechanism of effect of rotating constant magnetic field on organisms

The effect of RCMF-magnetic therapy apparatus on signal substances was studied. The radioimmunoassay (RIA) suggested that the magnetic field increased p-endorphin markedly in plasma. ELISA indicated that the magnetic field inhibited vomiting reaction induced by chemotherapy drug, with reversible decrease of serotonin (5-HT) level in brains, small intestine tissue and serum. Furthermore, the bioeffect of magnetic fields on 5-HT level presented a typical window effect and post-effect, and the inhibitory effect of magnetic field on the emesis was parallel to the decrease level of 5-HT. This result implied that the decrease of 5-HT might be the basis of rotating constant magnetic field (RCMF) inhibiting drug-induced emesis. The nitric acid reductase-spec-trophotometry and nicotinamide adenine dinucleotide-diaphorase/arginine-vasopressin (AVP) cytochemistry technique showed that the magnetic field induced nitric oxide (NO) increase in hypo-thalamus and the high NO(A) level lasted for 3 hours. The results sugg     

大鼠杏仁核5—HT3受体参与免疫调制

实验通过大鼠侧脑室和杏仁核给予5－HT3受体激动剂1－phenylbiguanide(PBG),用3H－TdR掺入法测定脾细胞丝裂原（concanavalin A,Con A和lipopolysaccharide,LPS)刺激增殖效应,用活化脾细胞增殖法测定IL－2生成,MTT法测定自然杀伤（natural killer,NK)细胞活性和用放射免疫测定血浆皮质酮水平,以探讨大鼠杏仁核5－HT3受体在免疫调控中的作用。结果表明：5－HT3受体拮抗剂granisetron(GNT,0.1-0.4mg/kg ip)剂量依赖地增强Con A和LPS刺激的脾细胞增殖,作用在连续给药5d最明显,双侧脑室给予PBG（5ug/side)可增强ConA和LPS刺激的脾细胞增殖效应,作用在连续给药3d最明显,双侧和单侧中共杏仁核给予PBG0．5ug均增强ConA刺激的脾细胞增殖和IL－2生成,底内侧杏仁核给予同剂量PBG仅增强LPS刺激的脾细胞增殖效应,不影响ConA刺激的脾细胞增殖和IL－2生成,中央杏仁核给予PBG升高血浆皮质酮的作用较底侧杏仁核给予等量PBG引起的升高血浆皮质酮作用明显（P＜0．01）,侧脑室,中央杏仁核和底内杏仁核给予PBG对丝裂原刺激的脾细胞增殖效应影响不同,但均被同时同部位给予GNT所拮抗,提示杏仁核中央核和底内侧核的5－HT3受体可能以不同方式参与ConA或LPS刺激的脾细胞增殖效应的调制。     

Molecular mechanism of effect of rotating constant magnetic field on organisms

The effect of RCMF-magnetic therapy apparatus on signal substances was studied. The radioimmunoassay (RIA) suggested that the magnetic field increased β-endorphin markedly in plasma. ELISA indicated that the magnetic field inhibited vomiting reaction induced by chemotherapy drug, with reversible decrease of serotonin (5-HT) level in brains, small intestine tissue and serum. Furthermore, the bioeffect of magnetic fields on 5-HT level presented a typical window effect and post-effect, and the inhibitory effect of magnetic field on the emesis was parallel to the decrease level of 5-HT. This result implied that the decrease of 5-HT might be the basis of rotating constant magnetic field (RCMF) inhibiting drug-induced emesis. The nitric acid reductase-spectrophotometry and nicotinamide adenine dinucleotide-diaphorase/arginine-vasopressin (AVP) cytochemistry technique showed that the magnetic field induced nitric oxide (NO) increase in hypothalamus and the high NO(A) level lasted for 3 hours. The results suggested that NO(A) increases after the treatment of the magnetic field in hypothalamus, which may result from strong expression of NO-ergic neuron in paraventricular hypothalamic nucleus (PVN), periventricular hypothalamic nucleus (PEN) and supraoptic nucleus (SON). The coexistence of NO and AVP may play an important role in the regulation of endocrine and neuroendocrine by the magnetic field. And our data also confirmed that the magnetic field increased the content of NO so strongly that high NO level lasted for 3 hours, also made neuropeptide Y (NPY) cell in medulla stained heavily.     

The negative immunoregulatory effects of serotonin (5-HT) moduline,an endogenous 5-HT1B receptor antagonist with anti-anxiety properties

BACKGROUND: Serotonin (5-HT) has negative immunoregulatory effects by reducing the interferon-gamma (IFNgamma)/interleukin-10 (IL-10) production ratio by stimulated immune cells. Leukocytes have functional 5-HT1B receptors. 5-HT moduline, an endogenous 5-HT1B receptor antagonist, may antagonize the 5-HT1B agonist-induced proliferation of immune cells. AIMS: To examine the effects of 5-HT moduline on the stimulated production of IFNgamma, tumor necrosis factor alpha (TNFalpha) and IL-10. RESULTS: 5-HT moduline, 10(-6) M and 10(-5)M, significantly reduced the production of IFNgamma and the IFNgamma/IL-10 ratio. 5-HT moduline 10(-5)M significantly reduced the production of TNFalpha. The combination of 5-HT, 15 microg/mL, with 5-HT moduline, 10(-6)M and 10(-5)M, further decreases the IFNgamma/IL-10 production ratio. INTERPRETATION: 5-HT moduline has negative immunoregulatory effects.     

Serotonin and epilepsy

In recent years, there has been increasing evidence that serotonergic neurotransmission modulates a wide variety of experimentally induced seizures. Generally, agents that elevate extracellular serotonin (5-HT) levels, such as 5-hydroxytryptophan and serotonin reuptake blockers, inhibit both focal and generalized seizures, although exceptions have been described, too. Conversely, depletion of brain 5-HT lowers the threshold to audiogenically, chemically and electrically evoked convulsions. Furthermore, it has been shown that several anti-epileptic drugs increase endogenous extracellular 5-HT concentration. 5-HT receptors are expressed in almost all networks involved in epilepsies. Currently, the role of at least 5-HT(1A), 5-HT(2C), 5-HT(3) and 5-HT(7) receptor subtypes in epileptogenesis and/or propagation has been described. Mutant mice lacking 5-HT(1A) or 5-HT(2C) receptors show increased seizure activity and/or lower threshold. In general, hyperpolarization of glutamatergic neurons by 5-HT(1A) receptors and depolarization of GABAergic neurons by 5-HT(2C) receptors as well as antagonists of 5-HT(3) and 5-HT(7) receptors decrease the excitability in most, but not all, networks involved in epilepsies. Imaging data and analysis of resected tissue of epileptic patients, and studies in animal models all provide evidence that endogenous 5-HT, the activity of its receptors, and pharmaceuticals with serotonin agonist and/or antagonist properties play a significant role in the pathogenesis of epilepsies.     

Dissecting the serotonergic food signal stimulating sensory-mediated aversive behavior in C. elegans

Nutritional state often modulates olfaction and in Caenorhabditis elegans food stimulates aversive responses mediated by the nociceptive ASH sensory neurons. In the present study, we have characterized the role of key serotonergic neurons that differentially modulate aversive behavior in response to changing nutritional status. The serotonergic NSM and ADF neurons play antagonistic roles in food stimulation. NSM 5-HT activates SER-5 on the ASHs and SER-1 on the RIA interneurons and stimulates aversive responses, suggesting that food-dependent serotonergic stimulation involves local changes in 5-HT levels mediated by extrasynaptic 5-HT receptors. In contrast, ADF 5-HT activates SER-1 on the octopaminergic RIC interneurons to inhibit food-stimulation, suggesting neuron-specific stimulatory and inhibitory roles for SER-1 signaling. Both the NSMs and ADFs express INS-1, an insulin-like peptide, that appears to cell autonomously inhibit serotonergic signaling. Food also modulates directional decisions after reversal is complete, through the same serotonergic neurons and receptors involved in the initiation of reversal, and the decision to continue forward or change direction after reversal is dictated entirely by nutritional state. These results highlight the complexity of the "food signal" and serotonergic signaling in the modulation of sensory-mediated aversive behaviors.     

Effect of vasoactive intestinal peptide on serotonin metabolism in the suprachiasmatic area of the rat: mechanism of action

Vasoactive intestinal peptide (VIP) inhibits serotonin (5-HT) uptake in the suprachiasmatic area (SCA) of the rat. The present study investigates the possibility of a functional relationship between 5-HT uptake mechanisms and 5-HT autoreceptor activity in this effect of VIP in the SCA. The hypothesis of a linkage between these two mechanisms of 5-HT regulation has been recently proposed. We investigated the possibility of the presence of 5-HT autoreceptors in the SCA. Using superfusion system, exogenous 5-HT (500 and 50 nM) increased the release of newly synthesized 3H-5-HT. In contrast, 5 nM of exogenous 5-HT inhibited this release. This latter effect was antagonized by methiothepin (10(-7) M). In contrast, the concentration of methiothepin required to inhibit the VIP effect was 10(-6) or 10(-5) M, the same molarity found to decrease the 5-HT uptake. On the other hand, the increase of the 3H-5-HT in the synaptic cleft, induced by VIP, did not modify the inhibition of 3H-5-HT release induced by 5 nM of exogenous 5-HT. We conclude that the effect of VIP on 5-HT metabolism in the SCA is linked to the 5-HT uptake mechanism but not to the activity of 5-HT presynaptic autoreceptors. In our experimental conditions, the activity of 5-HT autoreceptors is independent of the 5-HT uptake processes.     

The 5-HT2A serotoninergic receptor is expressed in the MCF-7 human breast cancer cell line and reveals a mitogenic effect of serotonin

Serotonin (5-hydroxytryptamine, 5-HT) has been described as a mitogen in a variety of cell types and carcinomas. It exerts its mitogenic effect by interacting with a wide range of 5-HT receptor types. Certain studies suggest that some selective serotonin re-uptake inhibitors promote breast cancer in animals and humans. This study attempts to clarify the role of serotonin in promoting the growth of neoplastic mammary cells. Expression of the 5-HT(2A) serotoninergic receptor subtype in MCF-7 cells was determined by RT-PCR, Western blotting, and immunofluorescence analysis. The mitogenic effect of 5-HT on MCF-7 cells was determined by means of the MTT proliferation assay. We have demonstrated that the 5-HT(2A) receptor subtype is fully expressed in the MCF-7 human breast cancer cell line, in terms of encoding mRNA and receptor protein. Automated sequencing has confirmed that the 5-HT(2A) receptor present in this cell line is identical to the 5-HT(2A) receptor found in human platelets and in human cerebral cortex. Furthermore, this receptor was found by immunofluorescence to be on the plasma membrane. MTT proliferation assays revealed that 5-HT and DOI, a selective 5-HT(2A) receptor subtype agonist, stimulated MCF-7 cell. These results indicate that 5-HT plays a mitogenic role in neoplastic mammary cells. Our data also indicate that 5-HT exerts this positive growth effect on MCF-7 cells through, in part, the 5-HT(2A) receptor subtype, which is fully expressed in this cell line.     

Detection and Characterization of the Serotonin 5-HT1D Receptor in Rat and Human Brain

In the presence of 1 microM ( +/- )-pindolol [to block 5-hydroxytryptamine (5-HT, serotonin) 5-HT 1A and 5-HT 1B receptors] and 100 nM mesulergine (to block 5-HT 1C receptors), 2.0 nM [3H]5-HT binding to rat cortical homogenates is specific, saturable, and reversible. Scatchard analysis of [3H]5-HT binding, in the presence of 1 microM ( +/- )-pindolol and 100 nM mesulergine, produced a KD of 3.2 nM and Bmax of 43 fmol/mg protein. Distribution studies show this site to be present in most rat brain regions. This site is also detectable in human caudate. The pharmacological profile of this site is distinct from the previously identified 5-HT receptor subtypes. Compounds with high affinity for 5-HT 1A (8-hydroxydipropylaminotetralin), 5-HT 1B (trifluoromethylphenylpiperazine), 5-HT 1C (mesulergine), 5-HT 2 (4-bromo-2,5-dimethoxyphenylisopropylamine), and 5-HT3 (ICS 205-930) receptors have low affinity for this site. These data suggest the presence of an additional, previously unidentified, 5-HT binding site in rat and human brain tissue. This putative novel 5-HT receptor has a similar pharmacology to the "5-HT 1D" site detected in bovine brain by Heuring and Peroutka.     

The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg439His knockin mouse

A decreased level of brain 5-hydroxytryptamine (5-HT) has been theorized to be a core pathogenic factor in depression for half a century. The theory arose from clinical observations that drugs enhancing extracellular levels of 5-HT (5-HT(Ext)) have antidepressant effects in many patients. However, whether such drugs indeed correct a primary deficit remains unresolved. Still, a number of anomalies in putative biomarkers of central 5-HT function have been repeatedly reported in depression patients over the past 40 years, collectively indicating that 5-HT deficiency could be present in depression, particularly in severely ill and/or suicidal patients. This body of literature on putative 5-HT biomarker anomalies and depression has recently been corroborated by data demonstrating that such anomalies indeed occur consequent to severely reduced 5-HT(Ext) levels in a mouse model of naturalistic 5-HT deficiency, the tryptophan hydroxylase 2 His(439) knockin (Tph2KI) mouse. In this review, we will critically assess the evidence for 5-HT deficiency in depression and the possible role of polymorphisms in the Tph2 gene as a causal factor in 5-HT deficiency, the latter investigated from a clinical as well as preclinical angle.     

5-Hydroxytryptamine2B receptors stimulate Ca2+ increases in cultured astrocytes from three different brain regions

The expression of 5-hydroxytryptamine-2B (5-HT2B) receptor mRNA has recently been shown in cultured astrocytes. Here the expression of functional 5-HT2B receptors has been studied in cultured astrocytes from rat cerebral cortex, hippocampus, and brain stem. Fluo-3- and fura-2-based microspectrofluorometry was used for measuring changes in intracellular free calcium concentrations ([Ca2+]i). The 5-HT2B agonist alpha-methyl 5-HT (40 nM) produced rapid transient increases in [Ca2+]i in astrocytes from all three brain regions studied, and these responses were blocked by the selective 5-HT2B antagonist rauwolscine (1 microM). The specificity of the responses to alpha-methyl 5-HT was further demonstrated by the failure of 4-(4-fluorobenzoyl)-1-(4-phenylbutyl)-piperidine oxalate (1 microM), a specific 5-HT2A/5-HT2C antagonist, to block these responses. The 5-HT2B-induced increases in [Ca2+]i persisted in Ca2+-free buffer, indicating that the increase in [Ca2+]i results from mobilization of intracellular Ca2+ stores. The expression of 5-HT2B receptors on astroglial cells was further verified immunohistochemically and by Western blot analysis. These results provide evidence of the existence of 5-HT2B receptors on astrocytes in primary culture.     

Role of 5-HT in the regulation of the brain-pituitary-adrenal axis: effects of 5-HT on adrenocortical cells

Serotonin (5-HT) plays a pivotal role in the regulation of the brain-pituitary-adrenal axis. In particular, 5-HT has been shown to control the activity of hypothalamic CRF neurons and pituitary corticotrope cells through activation of 5-HT1A and (or) 5-HT(2A/2C) receptor subtypes. 5-HT, acting through 5-HT2 receptors, can also trigger the renin-angiotensin system by stimulating renin secretion and consequently can enhance aldosterone production. At the adrenal level, 5-HT produced locally stimulates the secretory activity of adrenocortical cells through a paracrine mode of communication. The presence of 5-HT in the adrenal gland has been demonstrated immunohistochemically and biochemically in various species. In the frog, rat, and pig adrenal gland, 5-HT is synthesized by chromaffin cells, while in the mouse adrenal cortex, 5-HT is contained in nerve fibers. In man, 5-HT is present in perivascular mast cells. In vivo and in vitro studies have shown that 5-HT stimulates corticosteroid secretion in various species (including human). The type of receptor involved in the mechanism of action of 5-HT differs between the various species. In frogs and humans, the stimulatory effect of 5-HT on adrenocortical cells is mediated through a 5-HT4 receptor subtype positively coupled to adenylyl cyclase and calcium influx. In the rat, the effect of 5-HT on aldosterone secretion is mediated via activation of 5-HT7 receptors. Clinical studies indicate that 5-HT4 receptor agonists stimulate aldosterone secretion in healthy volunteers and in patients with corticotropic insufficiency and primary hyperaldosteronism. Local serotonergic control of corticosteroid production may be involved in the physiological control of the activity of the adrenal cortex as well as in the pathophysiology of cortisol and aldosterone disorders.     

Endogenous 5-HT2B receptor activation regulates neonatal respiratory activity in vitro

An implication of 5-HT(2B) receptors in central nervous system has not yet been clearly elucidated. We studied the role of different 5-HT(2) receptor subtypes in the medullary breathing center, the pre-B?tzinger complex, and on hypoglossal motoneurons in rhythmically active transversal slice preparations of neonatal rats and mice. Local microinjection of 5-HT(2) receptor agonists revealed tonic excitation of hypoglossal motoneurons. Excitatory effects of the 5-HT(2B) receptor agonist BW723C86 could be blocked by bath application of LY272015, a highly selective 5-HT(2B) receptor antagonist. Excitatory effects of the 5-HT(2A/B/C) receptor agonist alpha-methyl 5-HT could be blocked by the preferential 5-HT(2A) receptor antagonist ketanserin. Therefore, 5-HT-induced excitation of hypoglossal motoneurons is mediated by convergent activation of 5-HT(2A) and 5-HT(2B) receptors. Local microinjection of BW723C86 in the pre-B?tzinger complex increased respiratory frequency. Bath application of LY272015 blocked respiratory activity, whereas ketanserin had no effect. Therefore, endogenous 5-HT appears to support tonic action on respiratory rhythm generation via 5-HT(2B) receptors. In preparations of 5-HT(2B) receptor-deficient mice, respiratory activity appeared unaltered. Whereas BW723C86 and LY272015 had no effects, bath application of ketanserin disturbed and blocked rhythmic activity. This demonstrates a stimulatory role of endogenous 5-HT(2B) receptor activation at the pre-B?tzinger complex and hypoglossal motoneurons that can be taken up by 5-HT(2A) receptors in the absence of 5-HT(2B) receptors. The presence of functional 5-HT(2B) receptors in the neonatal medullary breathing center indicates a potential convergent regulatory role of 5-HT(2B) and -(2A) receptors on the central respiratory network.     

Development of Xenopus laevis skin glands producing 5-hydroxytryptamine and caerulein

Summary The granular glands in Xenopus laevis skin are known to contain large quantities of biogenic amines and bioactive peptides which closely resemble mammalian brain-gut peptides. We studied the development of glands producing 5-hydroxytryptamine (5-HT) and caerulein using immunohistochemistry, HPLC-fluorometric systems and RIA. The immunoreactivities of 5-HT and caerulein were first detected in the spherical gland rudiments in the stratum spongiosum at St. 58 (Nieuwkoop and Faber stage), or at the beginning of metamorphosis. Both immunoreactivities appeared in the same rudiment at the same time. Some of the gland rudiments have a small lumen filled with both immunoreactive materials at St. 58–59. During the rest of the metamorphic period, the glands grow in size, accumulating immunoreactive materials in the lumen. The concentrations of 5-HT and caerulein in the skin of tadpoles were below 1 ng per mg wet tissue at St. 58–59, increased as metamorphosis proceeded and reached 63 and 134 ng per mg wet tissue at St. 66, or at the end of metamorphosis, respectively. The amphibian granular glands where large quantities of biogenic amines and hormone-like peptides are rapidly synthesized may provide a useful model for the study of the development of amine- and peptide-producing cells including neurons and paraneurons.     

Serotonin augments gut pacemaker activity via 5-HT3 receptors

Serotonin (5-hydroxytryptamine: 5-HT) affects numerous functions in the gut, such as secretion, muscle contraction, and enteric nervous activity, and therefore to clarify details of 5-HT's actions leads to good therapeutic strategies for gut functional disorders. The role of interstitial cells of Cajal (ICC), as pacemaker cells, has been recognised relatively recently. We thus investigated 5-HT actions on ICC pacemaker activity. Muscle preparations with myenteric plexus were isolated from the murine ileum. Spatio-temporal measurements of intracellular Ca(2+) and electric activities in ICC were performed by employing fluorescent Ca(2+) imaging and microelectrode array (MEA) systems, respectively. Dihydropyridine (DHP) Ca(2+) antagonists and tetrodotoxin (TTX) were applied to suppress smooth muscle and nerve activities, respectively. 5-HT significantly enhanced spontaneous Ca(2+) oscillations that are considered to underlie electric pacemaker activity in ICC. LY-278584, a 5-HT(3) receptor antagonist suppressed spontaneous Ca(2+) activity in ICC, while 2-methylserotonin (2-Me-5-HT), a 5-HT(3) receptor agonist, restored it. GR113808, a selective antagonist for 5-HT(4), and O-methyl-5-HT (O-Me-5-HT), a non-selective 5-HT receptor agonist lacking affinity for 5-HT(3) receptors, had little effect on ICC Ca(2+) activity. In MEA measurements of ICC electric activity, 5-HT and 2-Me-5-HT caused excitatory effects. RT-PCR and immunostaining confirmed expression of 5-HT(3) receptors in ICC. The results indicate that 5-HT augments ICC pacemaker activity via 5-HT(3) receptors. ICC appear to be a promising target for treatment of functional motility disorders of the gut, for example, irritable bowel syndrome.     

5-Hydroxytryptamine as a potent migration enhancer of human aortic endothelial cells

The purpose of the present study was to investigate whether 5-hydroxytryptamine (5-HT, serotonin) affects migration of vascular endothelial cells. 5-HT significantly enhanced migration of human aortic endothelial cells (HAECs), and this enhancement was completely inhibited by GR 55562, a 5-HT1 receptor antagonist, and fluoxetine, a 5-HT transporter inhibitor, but was not affected by ketanserin, a 5-HT2 receptor antagonist. 5-HT stimulation increased RhoA and ERK activity of HAECs, and inhibitors of RhoA (Y-27632 and H-1152) and inhibitors of MEK (U0126 and PD98059) abolished the 5-HT-induced increase in migration velocity. Inhibition of Rho kinase by Y-27632 blocked stress fiber formation and rear release of HAECs. Thus, 5-HT has a potent enhancing action on migration of HAECs through activating the RhoA and ERK pathways following 5-HT1 receptor stimulation.