Structure-activity relationship of contractile effects induced by helicokinins in the isolated gut of the lepidopteran caterpillar Spodoptera frugiperda

The diuretic helicokinins YFSPWG-amide (Hez KI), VRFSPWG-amide (Hez KII) and KVKFSAWG-amide (Hez KIII) are potent contractants of the isolated gut of the caterpillar Spodoptera frugiperda at doses ranging from 0.1 to 10 nM. In comparison, the pentapeptide FSPWG-amide was a full agonist with greatly reduced potency while SPWG-amide and PWG-amide were weak partial agonists. Substitution of individual amino acids in Hez KI with alanine revealed that replacement of the [phenylalanine²] residue caused a large fall in potency while replacement of [tryptophan⁵] residue caused complete loss of myogenic activity. The striking fall in potency of YASPWG-amide and the lack of activity of YFSPAG-amide confirm the requirement for aromatic groups in positions 2 and 3 of the core pentapeptide as well as supporting the ideas that the active core of these peptides adopts a β-turn when interacting with receptors, bringing together the [Phe] and [Trp] residues that are critical for activity. Neither the pentapeptide proctolin nor the potent mammalian gut contractant Substance P were able to cause contraction when applied to caterpillar gut tissue. Incubation of isolated gut tissue in the phosphodiesterase inhibitor theophylline (10-100 μM) caused significant potentiation of the response to applied Hez KI. Conversely, in the presence of the L-type Ca²⁺ channel blocker verapamil (10 μM-1 mM) or Co²⁺ (1-50 mM) the contractile effects of Hez KI were attentuated significantly. These data suggest that the gut of S. frugiperda contains G-protein-linked kinin receptors that utilise cyclic AMP as their second messenger system and cause contraction by promoting the entry of extracellular Ca²⁺.     

Screening and characterization of lipase producing bacteria isolated from the gut of a lepidopteran larvae,Samia ricini

Lipolytic enzymes are an important group of hydrolases that have found immense industrial application in biotechnology. In this study, the ability of gut bacteria isolated from the gut of the Eri silkworm, Samia ricini, to produce lipolytic enzymes was evaluated through qualitative and quantitative assays. The results of lipase screening showed that 28 isolates had lipolytic activity. The results of 16S ribosomal RNA sequencing indicated that the genus Bacillus comprised majority of the lipolytic bacterial isolates (71%) followed by Pseudomonas (15%); whilst Acinetobacter, Enterobacter and Enterococcus comprised 11%. Lipolytic activity was found in bacteria isolates identified from all the three gut compartments of S. ricini larvae with significant activity from isolates extracted from the foregut and midgut. The lipolytic index among the bacterial isolates ranged between 0.63 and 2.81 on Rhodamine B medium, and all isolates exhibited significant lipolytic activity with p-nitrophenyl butyrate (PNPB) with specific activity ranging from 0.52 to 0.82 μmol/min/mg. The effect of pH and temperature showed that lipase activity was optimum at 37 °C and pH 7–9. A phylogenetic relationship of lipase producing gut bacteria indicated high cluster stability for isolates from different stages (>50%) suggesting that the isolates persist across developmental stages of the host. The Eri silkworm is reared for its silk and the knowledge of its gut bacteria with the ability to produce lipases lies in the significance as far as boosting production of this insect via development of probiotics to enhance commercial Eri rearing. In addition, this insect may be a good resource for profiling novel lipolytic microbes for commercial production of lipases as lipases from microbial origin have assumed a great deal of importance as industrial enzymes due to their potential for use in biotechnology.     

长爪沙鼠肠道5-羟色胺细胞密度的季节变化

为探讨季节性环境对长爪沙鼠肠道5-羟色胺(5-hydroxytryptamine,5-HT)细胞密度动态的影响,于2003
年11 月(冬季)和2004 年7 月(夏季),采用卵白素-生物素-过氧化物酶复合物(avidin-biotin-peroxidase complex,
ABC)免疫组织化学法,对其肠道5-HT 细胞进行了定位研究。结果显示:5-HT 细胞主要分布于肠上皮基
底部和肠腺上皮中,多呈圆形或椭圆形,少数呈长棒状、锥体形或不规则形,其形态学特征无季节性差异。冬
季在小肠密度最高,十二指肠、盲肠和直肠其次,结肠最低;夏季在小肠和十二指肠密度最高,其它各段密度
相似,这可能与其食物质量的季节性变化有关。除十二指肠和结肠外,冬季肠道各段的密度都高于夏季,这有
利于提高处理和消化食物的能力,是对冬季食物质量和摄食量增加的适应。5-HT 细胞的形态学特征和季节动态
说明,长爪沙鼠肠道在细胞水平上可对环境条件的变化产生反应,具有适应性调节的能力。     

5-Hydroxytryptamine-like immunoreactivity in the peripheral and central nervous systems of the leech Hirudo medicinalis

Summary Chains of segmental ganglia and various peripheral tissues from the leech (Hirudo medicinalis) were screened as whole-mount preparations for the presence of 5-hydroxytryptamine-like immunoreactivity. The gut was richly supplied with immunoreactive nerve fibres. Plexus of fibres, numerous of which were varicose, were found in the crop, with many immunopositive nerve cell bodies in the posterior region and a few in the anterior region. The intestine contained a few longitudinally oriented nerve fibres, while the rectum contained a dense network of non-varicose and varicose fibres. Fine immunopositive fibres were associated with the lateral blood vessel and reproductive organs. Many immunopositive nerve fibres ran in each of the paired connectives linking the segmental ganglia, and two fine varicose fibres were seen in Faivre's nerve. At least two immunopositive processes left each lateral segmental nerve and branched repeatedly, with many varicosities on the distal branches. The dorso-ventral and longitudinal body wall muscles both contained immunoreactive fibres, the plexus being more dense in the former muscle. The possible roles of the immunoreactive nerve fibres demonstrated in the various tissues of the leech have been discussed in relation to the known peripheral effects of serotoninergic neurone stimulation in the leech and to the actions of exogenously applied 5-hydroxytryptamine in these and other invertebrate tissues.     

Synthesis and Pharmacological Study of Rho-Kinase Inhibitors: Pharmacomodulations on the Lead Compound Fasudil

With a view to specifying structure–activity relationships we have synthesised a new series of analogues of the Rho-kinase inhibitor 1-(5-isoquinolinesulfonyl)-homopiperazine (Fasudil). The structural modifications concerned the isoquinolinyl heterocycle and the sulfonyl group which are the two main features of this lead compound. These analogues were evaluated on the actin cytoskeleton and on the enzymatic activity of Rho-kinase. Most of the chemical modifications result in a loss of activity showing that interactions of Fasudil with the catalytic domain of Rho-kinase seem to be particularly definite and sensitive to structural variations. The presence of an isoquinolinyl nitrogen and a basic amino group separated by a spacer bearing a sulfonamide function are of utmost importance. Only the tetrahydroisoquinoline analogue 3 shows the same activity as Fasudil. Moreover, this compound is unable to inhibit PKC biological activity contrary to Fasudil. The loss of the aromatic property could increase the selectivity level in favour of compound 3.     

Exogenous and endogenous protease inhibitors in the gut of the fall armyworm larvae,Spodoptera frugiperda

A dose‐dependent inhibition of endogenous trypsin and aminopeptidase occurs in the lumen of Spodoptera frugiperda after feeding L6 larvae exogenous inhibitors soybean trypsin inhibitor (SBTI), tosyl‐L‐lysine chloromethyl ketone‐HCl (TLCK), or bestatin, respectively, for 3 days. TLCK inhibits trypsin in tissue extracts and in secretions more strongly than SBTI. The aminopeptidase released into the lumen (containing the peritrophic membrane) is strongly inhibited by bestatin, but the membrane‐bound enzyme is not. A bound enzyme may be more resistant to an inhibitor than unbound. A cross‐class elevation of aminopeptidase activity occurs in response to ingested trypsin inhibitor, but there was no cross‐class effect of aminopeptidase inhibitor (bestatin) on trypsin activity. An endogenous trypsin and aminopeptidase inhibitor is present in the lumen and ventricular cells. The strength of the endogenous trypsin inhibition seems to be in the same range as that resulting from ingestion of the exogenous inhibitor SBTI. In some insect species, considerable trypsin secretion occurs in unfed as well as in fed animals, and endogenous protease inhibitors might function to protect the ventricular epithelium by inactivation of trypsin when less food is available. © 2010 Wiley Periodicals, Inc.     

Modulation of [3H]Paroxetine Binding to the 5-Hydroxytryptamine Uptake Site in an Animal Model of Depression

The effects of learned helplessness on the 5-hydroxytryptamine (5-HT) uptake site were studied in rats using [3H]paroxetine binding. This ligand was chosen because it was demonstrated to label directly the 5-HT uptake site whereas the [3H]imipramine binding site has been demonstrated to be heterogeneous in nature. Moreover, [3H]imipramine appears to bind to a presynaptic recognition site different from the uptake site. Exposure to uncontrollable shock training and testing resulted in an overall increase in [3H]paroxetine binding in all the groups studied [nonhelpless (NLH), learned helpless (LH), spontaneously helpless (SPLH)] as compared to naive controls (NC). However, the increase in [3H]paroxetine binding was significantly higher in the LH and SPLH groups. The maximum number of [3H]paroxetine binding sites in the rat hippocampus was increased significantly in learned helpless rats (LH and SPLH) at day 4 and day 30 after the shock escape test as compared to NC and NLH rats. By contrast, in the rat hypothalamus the maximum number of [3H]paroxetine binding sites was reduced significantly in the LH rats as compared to naive controls and NLH rats during the same time course. There was no change in [3H]paroxetine binding sites in any other brain regions examined in LH, NLH, and NC rats. The results suggest that a hippocampal hypothalamic connection might play a role in the serotonergic mediation of learned helpless behavior.     

A novel mutagen, 2-(5-hydroxy-4,6-dinitroindolyl) ethanol, formed in the reaction between 5-hydroxytryptamine and nitrite under acid conditions, especially in the presence of l-cysteine

We examined the mutagenic activity of each of 29 amino acids mixed under acidic conditions with 5-hydroxytryptamine (5-HT) and nitrite using Salmonella typhimurium strain TA 100 with or without a metabolic activation system (S9 mix). The reaction mixture containing l-cysteine was strongly mutagenic without S9 mix. We subjected an ethyl acetate extract of the reaction mixture to HPLC, isolated a mutagenic component, and investigated its chemical structure by LC–mass spectrometry (MS), high-resolution fast atom bombardment (HRFAB)-MS, and ¹H and ¹³C NMR. We identified the mutagen as 2-(5-hydroxy-4,6-dinitro-3-indolyl) ethanol (2HDIE). We injected 8 mg/kg 2HDIE i.p. into male ICR mice and found that the compound increased the frequency of micronuclei in peripheral reticulocytes. Our results suggest that 2HDIE might be formed in vivo by consumption of 5-HT, nitrite and l-cysteine in foods, and might act as a mutagen.     

Functional aspects of 5-hydroxytryptamine in early embryogenesis of the sea urchinParacentrotus lividus

Summary 5-Hydroxytryptamine concentrations have been determined in developing sea urchin embryos. Analysis was performed by thin layer chromatography and by fluorimetry. Good correspondence of the results between the two methods was observed. 5-HT was found in the larvae from 33 h of age. The content increased as development proceeded. Treatment of the larvae with iproniazid did not alter the 5-HT content, in contrast to N,N-dimethyltryptamine which caused an increase of the monoamine. The accumulation is thought to depend upon the development of a storage mechanism but the synthesis is considered to start before this storage mechanism is developed. It is suggested that 5-HT is active both at an intracellular and an intercellular level. The intracellular 5-HT acts directly or indirectly on the contractile elements involved in the system responsible for the motility of the cells. In more advanced stages 5-HT acts at an intercellular level as well. In this case it is suggested that the function of 5-HT is analogous to its function in nerve tissue.     

Two Amino Acid Differences in the Sixth Transmembrane Domain Are Partially Responsible for the Pharmacological Differences Between the 5-HT1Dβ and 5-HT1E 5-Hydroxytryptamine Receptors

Abstract: 5-Hydroxytryptamine elicits its physiological effects by interacting with a diverse group of receptors. Two of these receptors, the 5-HT_1Dβ and the 5-HT_1E receptors, are ∼60% identical in the transmembrane domains that presumably form the ligand binding site yet have very different pharmacological properties. Analysis of the pharmacological properties of a series of chimeric 5-HT_1Dβ/5-HT_1E receptors indicates that sequences in the sixth and seventh transmembrane domains are responsible for the differential affinity of 5-carboxamidotryptamine for these two receptors. More detailed analysis shows that two amino acid differences in the sixth transmembrane domain (Ile³³³ and Ser³³⁴ in the 5-HT_1Dβ receptor, corresponding to Lys³¹⁰ and Glu³¹¹ in the 5-HT_1E receptor) are largely responsible for the differential affinities of some, but not all, ligands for the 5-HT_1Dβ and 5-HT_1E receptors. It is likely that these two amino acids subtly determine the overall three-dimensional structure of the receptor rather than interact directly with individual ligands.     

Characterization of the gut microbiome in the beet armyworm Spodoptera exigua in response to the short-term thermal stress

The gut microbiota is critical for energy and nutrient utilization and plays a role in host immunity in response to environmental changes. The beet armyworm Spodoptera exigua is a worldwide polyphagous agricultural pest and has frequently experienced potentially stressful temperature fluctuations under natural environmental conditions. However, little is known about the effects of thermal stress on the gut microbiome of this moth pest. Therefore, we investigated the gut microbiome variations, composition and community structure of S. exigua among low-temperature (10 °C), control (26 °C) and high temperature (35 °C) treatments using 16S amplicon sequencing. Overall, 1,192,707 high-quality reads and 762 operational taxonomic units (OTUs) were detected from 15 samples. A total of 289 genera belonging to 19 bacterial phyla were captured, with Firmicutes and Proteobacteria being the most prominent phyla. Alpha diversity metrics indicated no significant differences in the gut bacterial diversity of S. exigua among the three temperature treatments. Principal coordinates and hierarchical cluster analysis revealed significant differences in the structure of gut microbiota between the low-temperature treatment and the other two temperature treatments. In addition, PICRUSt2 analysis demonstrated that the predicted metagenomes associated with the gut microbiome were amino carbohydrate transport and metabolism, acid transport and metabolism, inorganic ion transport and metabolism and cellular processes. Our study showed that thermal stress induced changes in the gut microbiome of the beet armyworm, which may contribute to better understanding the ecological adaptation of S. exigua under changing temperature trends and to evaluating the use of gut microorganisms as biocontrol agents for this pest.     

Pharmacological Differentiation and Characterization of 5-HT1A, 5-HT1B, and 5-HT1C Binding Sites in Rat Frontal Cortex

Drug interactions with 5-HT1 (5-hydroxytryptamine type 1) binding site subtypes were analyzed in rat frontal cortex. 8-Hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) displays high affinity (Ki 3.3 +/- 1 nM) for 29 +/- 3% of total [3H]5-HT binding in rat frontal cortex and low affinity (Ki 9,300 +/- 1,000) for 71 +/- 4% of the remaining 5-HT1 sites. Therefore, non-5-HT1A binding in rat frontal cortex was defined as specific [3H]5-HT binding observed in the presence of 100 nM 8-OH-DPAT. 5-Methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl) 1 H indole (RU 24969), 1-(m-trifluoromethylphenyl)piperazine (TFMPP), mianserin, and methysergide produce shallow competition curves of [3H]5-HT binding from non-5-HT1A sites. Addition of 10(-3) M GTP does not increase the apparent Hill slopes of these competition curves. Computer-assisted iterative curve fitting suggests that these drugs can discriminate two distinct subpopulations of non-5-HT1A binding sites, each representing approximately 35% of the total [3H]5-HT binding in the rat frontal cortex. All three 5-HT1 binding site subtypes display nanomolar affinity for 5-HT and 5-methoxytryptamine. A homogeneous population of 5-HT1A sites can be directly labeled using [3H]8-OH-DPAT. These sites display nanomolar affinity for 8-OH-DPAT, WB 4101, RU 24969, 2-(4-[4-(2-pyrimidinyl)-1-piperazinyl] butyl)-1,2-benzisothiazol-3-(2H)one-1, 1-dioxidehydrochloride (TVX Q 7821), 5-methoxydimethyltryptamine, and d-lysergic acid diethylamide. The potencies of RU 24969, TFMPP, and quipazine for [3H]5-HT binding are increased by addition of 100 nM 8-OH-DPAT and 3,000 nM mianserin to the [3H]5-HT binding assay. Moreover, the drugs have apparent Hill slopes near 1 under these conditions. This subpopulation of total [3H]5-HT binding is designated 5-HT1B. By contrast, methysergide and mianserin become more potent inhibitors of residual [3H]5-HT binding to non-5-HT1A sites in the presence of 100 nM 8-OH-DPAT and 10 nM RU 24969. The drug competition curves under these conditions have apparent Hill slopes of near unity and these sites are designated 5-HT1C. Drug competition studies using a series of 24 agents reveals that each 5-HT1 subtype site has a unique pharmacological profile. These results suggest that radioligand studies can be used to differentiate three distinct subpopulations of 5-HT1 binding sites labeled by [3H]5-HT in rat frontal cortex.     

Differential Effects of Ipsapirone on 5-Hydroxytryptamine Release in the Dorsal and Median Raphe Neuronal Pathways

Abstract: Serotonergic neurons of the dorsal and median raphe nuclei are morphologically dissimilar. Recent results challenge previous evidence indicating a greater inhibition of dorsal raphe neurons after 5-hydroxytryptamine_1A (5-HT_1A) autoreceptor activation. As both nuclei innervate different forebrain territories, this issue is critical to understanding the changes in brain function induced by anxiolytic and antidepressant drugs. Using microdialysis, we examined the modifications of 5-HT release induced by the selective 5-HT_1A agonist ipsapirone in both neuronal pathways. Maximal and minimal basal 5-HT values (in the presence of 1 µ M citalopram) were 45.0 ± 4.8 fmol/fraction in the median raphe nucleus and 8.4 ± 0.4 fmol/fraction in the dorsal hippocampus. Ipsapirone (0.3, 3, and 10 mg/kg s.c.) reduced dose-dependently 5-HT in the two raphe nuclei and four forebrain areas. Maximal reductions (to ∼25% of predrug values) were observed in cortex and striatum and in median raphe nucleus. The effects were more moderate in dorsal and ventral hippocampus (to 66 and 50% of baseline, respectively). These results are consistent with a higher sensitivity of dorsal raphe neurons to 5-HT_1A autoreceptor activation. Yet the differential reduction of 5-HT release in the median raphe nucleus and hippocampus suggests the presence of complex mechanisms of control of 5-HT release in these neurons.     

基于非靶向代谢组学分析取食玉米和水稻后草地贪夜蛾肠道代谢谱的差异

为了探究草地贪夜蛾Spodoptera frugiperda J. E. Smith在不同寄主上的适应性,本试验采用室内饲养观察法比较其取食玉米Zea mays L.和水稻Oryza sativa L.叶片后的发育、存活和繁殖,同时,对草地贪夜蛾4龄幼虫肠道进行解剖,运用代谢组学分析方法,探究幼虫在分别取食两种寄主植物（玉米/水稻）后肠道代谢谱的差异,筛选与不同寄主取食相关的重要代谢物及代谢通路。结果显示,相较取食玉米叶片（对照组）,取食水稻叶片（试验组）的世代周期延长（38.05±0.35 d）,成虫前期存活率下降（0.46±0.01）,生命表参数中净繁殖力R0（191.68±33.54）、内禀增长率r（0.125±6.77）、周限增长率λ（1.133±7.65）均低于对照组;肠道代谢谱中,共有750个差异代谢物,其中下调587个,上调163个,取食水稻叶片较取食玉米叶片的草地贪夜蛾幼虫肠道中,下调的差异代谢物主要包括组氨酸、α-亚麻酸（ALA）和莽草酸;上调的代谢物有天冬酰胺基半胱氨酸以及N-乙酰氨基甲酸等,这些代谢物涉及氨基酸代谢和脂质代谢等通路。本研究结果可为草地贪夜蛾取食不同寄主的适应机制提供了线索。     

Characterisation of Inhibitory 5-Hydroxytryptamine Receptors That Modulate Dopamine Release in the Striatum

Abstract: The effect of a series of indoleamines on the potassium-evoked tritium release of previously accumulated [³H]dopamine from rat striatal slices has been investigated. The indoleamines 5-hydroxytryptamine, 5-methoxy-tryptamine, 5-methoxy- N, N' -dimethyltryptamine and tryptamine (10⁻⁷ to 10⁻³ M) all reduced potassium-evoked release of tritium, to a maximum of 50%. The uptake of [³H]dopamine was unaffected by these compounds. A series of 5-hydroxytryptamine antagonists were examined for their ability to reduce the inhibition of potassium-evoked tritium release induced by 5-methoxytryptamine. The relative order of antagonist potency obtained was methysergide > metergoline > methiothepin > cinanserin > cyproheptadine > mianserin, and was consistent with an action on 5-hydroxytryptamine receptors. It is concluded that there are inhibitory 5-hydroxytryptamine receptors located on the terminals of dopaminergic neurones in the striatum.     

Deamination of 5-Hydroxytryptamine by Both Forms of Monoamine Oxidase in the Rat Brain

Abstract: K _m and V _max values of monoamine oxidase (MAO) A and B towards 5-hydroxytryptamine were determined for rat brain homogenates after the in vitro inhibition of one of the two forms by the selective inhibitors clorgyline and l -deprenyl. K _m values of 178 and 1170μ m , and V _max values of 0.73 and 0.09 nmol·mg protein⁻¹·min⁻¹ towards 5-hydroxytryptamine were found for MAO-A and -B, respectively. The K ₁ for 5-hydroxytryptamine as a competitive inhibitor of β-phenethylamine oxidation by MAO-B was found to be 1400 μm. The significance of these findings is discussed.     

Regional Distribution of Extracellular 5-Hydroxytryptamine and 5-Hydroxyindoleacetic Acid in the Brain of Freely Moving Rats

The extracellular concentrations of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been determined in six brain areas of awake rats (frontal cortex, striatum, hypothalamus, hippocampus, inferior colliculus, and raphe nuclei) using intracerebral microdialysis. The extracellular levels of 5-HT showed no significant differences among the brain regions studied. The tissue levels of 5-HT and 5-HIAA as well as the extracellular concentration of 5-HIAA were significantly higher in raphe nuclei. The regional distribution of tissue and extracellular 5-HIAA were very similar, suggesting that extracellular 5-HIAA depends mainly on the output from the intracellular compartment. On the other hand, extracellular 5-HT and tissue 5-HT showed a different distribution pattern. The tissue/extracellular ratio for 5-HT ranged from 739 in frontal cortex to 2,882 in raphe, whereas it only amounted to 1.8-3.6 for 5-HIAA. The relationship between the present results and the density of 5-HT uptake sites in these areas is discussed.     

Regulation of Serotonin Release in the Frontal Cortex and Ventral Hippocampus of Homozygous Mice Lacking 5-HT1B Receptors: In Vivo Microdialysis Studies

Abstract: To assess the involvement of the serotonin receptor subtype 5-HT_1B as terminal autoreceptor regulating 5-HT release in mice, we compared basal values and potassium-evoked changes of extracellular 5-HT levels obtained by in vivo microdialysis in two serotoninergic terminal projection areas of conscious wild-type mice with those measured in homozygous mutant mice lacking the gene encoding the 5-HT_1B receptor. In the frontal cortex and ventral hippocampus, basal and K⁺-evoked 5-HT release did not differ between the two strains of mice studied. The infusion via reverse microdialysis of the selective 5-HT_1B receptor agonist CP-93,129 (500 n M ) decreased significantly K⁺-evoked 5-HT release in the frontal cortex (by −44%) and ventral hippocampus (by −32%) of wild-type mice but had no effect in mutants. In a similar manner, the mixed 5-HT_1B-5-HT_1D receptor agonist sumatriptan (800 n M ) decreased significantly K⁺-evoked 5-HT release in the frontal cortex (by −46%) of wild-type mice but had no effect in mutants. These results demonstrated that 5-HT_1B knockout mice are not as sensitive to full (CP-93,129) and mixed (sumatriptan) 5-HT_1B receptor agonists as are wild-type mice. These data provide in vivo evidence that, in mice, 5-HT_1B, but not 5-HT_1D, autoreceptors inhibit 5-HT release at nerve terminals located in the frontal cortex and ventral hippocampus.     

The effect of the selective 5-HT(3) receptor agonist on ferret gut motility

The effect of the selective 5-hydroxytryptamine (5-HT)(3) receptor agonist YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate) on gut motility of fed ferrets was investigated. YM-31636 (0.1 mg/kg p.o.) induced a giant migrating contraction (GMC)-like, high-amplitude, ungrouped colonic contraction although it did not change the basal colonic motility pattern. This GMC-like contraction was always accompanied by defecation. Both GMC-like contraction and defecation were inhibited with the selective 5-HT(3) receptor antagonist ramosetron. YM-31636 affected gastric, duodenal and ileal motility pattern only slightly. These results suggest that 5-HT(3) receptor agonists such as YM-31636 are useful in treating constipation since they facilitate GMC-like contractions and defecation without undesired changes in gut motility pattern.