piperidines and azasetron

To investigate the effects of a water extract of Hwangryunhaedok-tang (HHTE) on the pacemaker potentials of mouse interstitial cells of Cajal (ICCs).. We dissociated ICCs from small intestines and cultured. ICCs were immunologically identified using an anti-c-kit antibody. We used the whole-cell patch-clamp configuration to record the pacemaker potentials generated by cultured ICCs under the current clamp mode (. HHTE dose-dependently depolarized ICC pacemaker potentials. Pretreatment with a 5-HT. These results suggest that HHTE dose-dependently depolarizes ICC pacemaker potentials through 5-HT

Topics: Animals; Biological Clocks; Bridged Bicyclo Compounds, Heterocyclic; Calcium; Cells, Cultured; Drugs, Chinese Herbal; Enzyme Inhibitors; Gastrointestinal Motility; GTP-Binding Proteins; Interstitial Cells of Cajal; Intestine, Small; Membrane Potentials; Mice; Mice, Inbred ICR; Oxazines; Patch-Clamp Techniques; Phenols; Piperidines; Plant Extracts; Propane; Protein Kinase C; Receptors, Serotonin; rho-Associated Kinases; Serotonin 5-HT3 Receptor Antagonists; Serotonin 5-HT4 Receptor Antagonists; Sulfonamides; Thapsigargin

Interactions between the cannabinoid and serotonin systems have been reported in many studies. In the present study, we investigated the influence of the serotonergic receptor agents on amnesia induced by the cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA). Bilateral guide-cannulae were implanted to allow intra-CA3 microinjection of the drugs. The results showed that the intra-peritoneal (i.p.) injection of ACPA induce amnesia but did not alter head dip latency, head dip counts, and locomotion. Moreover, intra-CA3 injection of M-Chlorophenylbiguanide (M-CHL, a 5-HT3 serotonin receptor agonist), Y-25130 (a 5-HT3 serotonin receptor antagonist), RS67333 (a 5-HT4 serotonin receptor agonist), and RS23597-190 (a 5-HT4 serotonin receptor antagonist) impaired memory but have no effect on head dip latency and locomotor activity. In addition, intra-CA3 injection of Y-25130, RS67333, and RS23597-190 heighten the ACPA-induced amnesia and head dip counts while did not alter head dip latency and locomotor activity. On the other hand, intra-CA3 microinjection of M-CHL could not modify the ACPA-induced amnesia, head dip latency and locomotor activity whereas increased head dip counts. It can be concluded that the amnesia induced by i.p. administration of ACPA is at least partly mediated through the serotonergic receptor mechanism in the CA3 area.

Topics: Amnesia; Aniline Compounds; Animals; Arachidonic Acids; Biguanides; Bridged Bicyclo Compounds, Heterocyclic; CA3 Region, Hippocampal; Cannabinoid Receptor Agonists; Catheters, Indwelling; Male; Mice; Oxazines; para-Aminobenzoates; Piperidines; Receptor, Cannabinoid, CB1; Receptors, Serotonin, 5-HT3; Receptors, Serotonin, 5-HT4; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists

The present study examined the effects of administering selective 5-HT antagonists and agonists to rats tested in the elevated zero-maze (EZM) model of anxiety. The EZM paradigm has advantages over the elevated plus-maze (EPM) paradigm with respect to measuring anxiety, yet has been utilized less frequently. Three experiments were conducted each with a diazepam control (0.25, 0.5 and 0.75 mg/kg). In the first experiment, we administered the 5-HT2C antagonist RS 102221 (0.5, 1.0, and 2.0 mg/kg) and 5-HT2C agonist MK-212 (0.25, 0.5 and 0.75 mg/kg); in the second experiment, we administered the 5-HT3 antagonist Y-25130 (0.1, 1.0 and 3.0 mg/kg) and 5-HT3 agonist SR 57227A (0.1, 1.0 and 3.0 mg/kg), and in the third experiment, we administered the 5-HT4 antagonist RS 39604 (0.01, 0.1, 1.0 mg/kg) and 5-HT4 agonist RS 67333 (0.01, 0.1 and 0.5 mg/kg). The administration of 5-HT2/3/4 subtype antagonists all generated behavioral profiles indicative of anxiolytic-like effects in the EZM, which was apparent from examination of both traditional and ethological measures. While little effect was observed from 5-HT2 and 5-HT3 agonists, the 5-HT4 agonist RS 67333 was found to produce a paradoxical anxiolytic-like effect similar to that produced by the 5-HT4 antagonist RS 39604. We conclude by discussing the implications of these findings.

Topics: Aniline Compounds; Animals; Anti-Anxiety Agents; Anxiety; Behavior, Animal; Bridged Bicyclo Compounds, Heterocyclic; Diazepam; Male; Maze Learning; Oxazines; Piperidines; Propane; Pyrazines; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Spiro Compounds; Sulfonamides

Serotonin (5HT) has been shown to be a mitogenic factor in several carcinomas. Its mitogenic effect is elicited through a wide range of 5HT receptor subtypes. In this study, the effects of 5HT, 5HT3 (1-phenylbiguanide hydrochloride) and 5HT4 (cisapride) agonists in promoting the growth of the HT29 cell line and the growth-inhibition effect of the 5HT3 receptor antagonist (Y-25130 hydrochloride) and 5HT4 receptor antagonist (RS 23597-190) were investigated. The expressions of 5HT3 and 5HT4 receptors in human colon cancer tissues and the HT29 cell line were studied.. The growth-promoting and growth-inhibition effects of 5-HT, 5HT3 and 5HT4 agonists and antagonists on the HT29 cell line were studied using MTT assay. Receptor expression has been demonstrated by western blotting.. The results showed that 5HT, 5HT3, and 5HT4 agonists caused significant proliferation of HT29 cells. 5HT3 and 5HT4 receptor antagonists had an inhibitory effect on the growth of these cells. Western blot analysis gave bands from colon tissue extracts and the HT29 cell line.. The results indicate which 5HT3 and 5HT4 receptors are significantly expressed in both colon cancer tissue and the HT29 cell line. Expression for the 5HT3 receptor is more potent. Furthermore, 5HT plays a mitogenic role in colon cancer cells and antagonists of 5HT3, and 5HT4 receptors can inhibit cancer cell growth.

Topics: Adenocarcinoma; Aminobenzoates; Biguanides; Blotting, Western; Bridged Bicyclo Compounds, Heterocyclic; Cell Proliferation; Cisapride; Colonic Neoplasms; HT29 Cells; Humans; Oxazines; para-Aminobenzoates; Piperidines; Receptors, Serotonin, 5-HT3; Receptors, Serotonin, 5-HT4; Serotonin 5-HT3 Receptor Agonists; Serotonin 5-HT3 Receptor Antagonists; Serotonin 5-HT4 Receptor Agonists; Serotonin 5-HT4 Receptor Antagonists

The neurotransmitter 5-hydroxytryptamine (5-HT), commonly known as serotonin, is released at peripheral sites from activated enterochromaffin cells, mast cells and platelets. In this study we analyzed the biological activity and intracellular signaling of 5-HT in human monocytes. By reverse transcription (RT) and PCR, messenger RNA (mRNA) expression of 5-HT receptor 1E (5-HTR(1E)), 5-HTR(2A), 5-HTR(3), 5-HTR(4) and 5-HTR(7) could be revealed. Functional studies showed that 5-HT modulates the release of IL-1beta, IL-6, IL-8/CXCL8, IL-12p40 and tumor necrosis factor-alpha (TNF-alpha), while it has no effect on the production of IL-18 and IFN-gamma in LPS-stimulated human blood monocytes. Moreover, RT and PCR revealed that 5-HT modulated mRNA levels of IL-6 and IL-8/CXCL8, but did not influence mRNA levels of IL-1beta and TNF-alpha. Pharmacological studies with isotype-selective receptor agonists allowed us to show that 5-HTR(3) subtype up-regulates the LPS-induced production of IL-1beta, IL-6 and IL-8/CXCL8, while it was not involved in TNF-alpha and IL-12p40 secretion. Furthermore, activation of the G(s)-coupled 5-HTR(4) and 5-HTR(7) subtypes increased intracellular cyclic AMP (cAMP) and secretion of IL-1beta, IL-6, IL-12p40 and IL-8/CXCL8, while, on the contrary, it inhibited LPS-induced TNF-alpha release. Interestingly, 5-HTR(1) and 5-HTR(2) agonists did not modulate the LPS-induced cytokine production in human monocytes. Our results point to a new role for 5-HT in inflammation by modulating cytokine production in monocytes via activation of 5-HTR(3), 5-HTR(4) and 5-HTR(7) subtypes.

Topics: Bridged Bicyclo Compounds, Heterocyclic; Cells, Cultured; Chemokines; Cytokines; Free Radical Scavengers; Humans; Lipopolysaccharides; Monocytes; Oxazines; Phenols; Piperidines; Propane; Receptors, Serotonin; RNA; Serotonin; Serotonin Antagonists; Sulfonamides; Tumor Necrosis Factor-alpha

The aim of the present study was to investigate the modulation of locus coeruleus neurons by the selective serotonin (5-HT) reuptake inhibitor citalopram using single-unit extracellular recordings in rat brain slices. Citalopram inhibited the activity of a subpopulation of locus coeruleus neurons; thus 10 microM citalopram inhibited neurons by 53+/-17% (5 out of 15 cells), whereas the inhibition due to 100 microM was 64+/-4% (32 out of 42 cells). This effect was partially reversed (47+/-11%) by the alpha(2)-adrenoceptor antagonist idazoxan (10 microM), whereas it was unaffected by antagonists for 5-HT(1A), 5-HT(2,) and 5-HT(3) receptors, and mu opioid receptors. 5-HT (50 or 200 microM), the 5-HT(1A) receptor agonist 8-OH-DPAT (+/-)-8-hydroxy-2-(DI-n-propyl-amino) tetralin hydrobromide, 10 microM) and the 5-HT(2) receptor agonist DOI ([+/-]-2,5-dimetoxy-4-iodoamphetamine) hydrochloride, 10 or 30 microM) also inhibited a subpopulation of locus coeruleus cells. In addition, citalopram but not 5-HT, enhanced by 1.7 fold the inhibitory effect of noradrenaline. Long-term treatment with citalopram (20 mg/kg/day) did not modify the effect of noradrenaline and bromoxidine. Taken together, our results indicate that citalopram exerts an inhibitory effect on locus coeruleus noradrenergic neurons. alpha(2)-adrenoceptor activation may underlie this effect as a result of elevated levels of noradrenaline in the synaptic cleft.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Action Potentials; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Amphetamines; Animals; Bridged Bicyclo Compounds, Heterocyclic; Brimonidine Tartrate; Citalopram; Dose-Response Relationship, Drug; Duloxetine Hydrochloride; Idazoxan; In Vitro Techniques; Locus Coeruleus; Male; Methiothepin; Naloxone; Narcotic Antagonists; Neurons; Norepinephrine; Oxazines; Piperazines; Piperidines; Pyridines; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-2; Receptors, Opioid, mu; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Thiophenes

1. Experiments were carried out in conscious, chronically instrumented, male, Sprague-Dawley rats to delineate the regional haemodynamic effects of the putative endogenous cannabinoid, anandamide, (0.075 - 3 mg kg(-1)), and to dissect some of the mechanisms involved. 2. At all doses of anandamide, there was a significant, short-lived increase in mean arterial blood pressure associated with vasoconstriction in renal, mesenteric and hindquarters vascular beds. 3. The higher doses (2.5 and 3 mg kg(-1)), caused an initial, marked bradycardia accompanied, in some animals, by a fall in arterial blood pressure which preceded the hypertension. In addition, after the higher doses of anandamide, the hindquarters vasoconstriction was followed by vasodilatation. 4. Although some of the effects described above resembled those of 5-HT (25 microg kg(-1)), the bradycardia and hypotensive actions of the latter were abolished by the 5HT(3)-receptor antagonist, azasetron, whereas those of anandamide were generally unaffected. 5. None of the cardiovascular actions of anandamide were influenced by the CB(1)-receptor antagonist, AM 251, but its bradycardic effect was sensitive to atropine, and its hindquarters vasodilator action was suppressed by the beta(2)-adrenoceptor antagonist, ICI 118551. 6. The results differ, in several aspects, from those previously reported in anaesthetized animals, and underscore the important impact anaesthesia can have on responses to anandamide.

Topics: Adrenergic beta-Agonists; Animals; Arachidonic Acids; Atropine; Bridged Bicyclo Compounds, Heterocyclic; Calcium Channel Blockers; Consciousness; Dose-Response Relationship, Drug; Endocannabinoids; Hemodynamics; Hindlimb; Male; Oxazines; Piperidines; Polyunsaturated Alkamides; Propanolamines; Pyrazoles; Rats; Rats, Sprague-Dawley; Renal Circulation; Serotonin; Serotonin Antagonists; Sodium Chloride; Splanchnic Circulation; Wakefulness