rs-39604 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

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

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