Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 5-HT3 receptor antagonists ICS 205-930 and zacopride attenuated cocaine-induced locomotor activity in C57BL/6ByJ mice. In contrast, the aselective 5-HT1 and 5-HT2 receptor antagonist, methysergide did not affect the response to cocaine. The effect of the 5-HT3 receptor antagonists was not due to general sedation, because zacopride did not alter the locomotor response to caffeine.
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PMID:5-HT3 receptor antagonists attenuate cocaine-induced locomotion in mice. 228 34

1. We devised a new light/dark transition apparatus, recorded transitions, % time animals spent outside the dark chambers (% time) and locomotor activity, and evaluated this apparatus by testing anxiolytics, non-anxiolytic drugs and putative anxiogenic drugs in mice. 2. Diazepam and alprazolam significantly increased transitions, % time and locomotor activity. The effects of 1 mg/kg (i.p.) diazepam on these parameters in this modified test were blocked by flumazenil, a selective benzodiazepine antagonist. 3. Anxiogenic drugs such as beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) and picrotoxin significantly decreased all three parameters. Another anxiogenic drug, yohimbine, also significantly decreased transitions and locomotor activity, but it significantly increased % time at 5 mg/kg (i.p.). 4. Imipramine (5-10 mg/kg, i.p.), an antidepressant, sulpiride (10-25 mg/kg, i.p.), an antipsychotic drug, and scopolamine (0.1-1 mg/kg, i.p.), an anticholinergic drug, had no effect. 5. Buspirone, a partial 5-HT1A receptor agonist, produced parameter changes similar to those induced by anxiolytic benzodiazepines. 8-OH-DPAT, a full 5-HT1A receptor agonist, significantly increased transitions and locomotor activity but not % time. 5-HT3 receptor antagonists, ICS205-930 and MDL72222, did not have any effect on these parameters. 6. Methamphetamine (1-2 mg/kg, i.p.) increased all parameters, while caffeine increased only locomotor activity. 7. The present findings indicate that the modified light/dark transition test is very simple and easy to perform for testing the anxiolytic and anxiogenic effects of drugs.
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PMID:The modified light/dark transition test in mice: evaluation of classic and putative anxiolytic and anxiogenic drugs. 771 61

We have used single-cell imaging of fura-2-loaded cells to examine the Ca2+ signals evoked by activation of 5-hydroxytryptamine type 3 (5-HT3) receptors in undifferentiated N1E-115 neuroblastoma cells and in human embryonic kidney (HEK) 293 cells transfected with either of the two cloned 5-HT3 receptor subunits. The selective 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (mCPBG) caused a concentration-dependent increase in the cytoplasmic Ca2+ concentration ([Ca2+]i) in N1E-115 cells and in HEK 293 cells transfected with either the 5-HT3 A subunit or the 5-HT3 As subunit. In each case, the [Ca2+]i rise was steeply dependent on the mCPBG concentration (nH = 2-4) and abolished by removal of extracellular Ca2+ or addition of ondansetron. Pretreatment of N1E-115 cells with thapsigargin, caffeine, and ryanodine to deplete intracellular Ca2+ stores had no effect on the mCPBG-evoked Ca2+ signals, indicating that they result entirely from stimulated Ca2+ entry. The steep concentration-effect curves therefore are not a consequence of amplification of Ca2+ influx by Ca(2+)-induced Ca2+ release from intracellular stores and probably reflect cooperative activation of 5-HT3 receptors by mCPBG. Depolarization of transfected HEK 293 cells with medium containing increased K+ concentrations invariably failed to evoke an increase in [Ca2+]i, confirming the absence of voltage-gated Ca2+ channels and indicating that the mCPBG-evoked rise in [Ca2+]i results from Ca2+ permeation of 5-HT3 receptors. However, in N1E-115 cells and transfected HEK 293 cells, both extracellular Na+ and K+ substantially inhibited the Ca2+ influx evoked by activation of 5-HT3 receptors, possibly by inhibition of agonist binding or by competition with Ca2+ for permeation of the channel. We conclude that 5-HT3 receptors are Ca2+ permeant, that the Ca2+ influx is sufficient to generate a significant rise in [Ca2+]i, and that, because the A and As subunits behave similarly, conflicting electrophysiological analyses of Ca2+ currents cannot be explained by differences between these two subunits.
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PMID:Ca2+ permeability of cloned and native 5-hydroxytryptamine type 3 receptors. 780 32

A complete understanding of how excitatory ligand-gated ion channels regulate intracellular Ca2+ in nerve cells remains to be elucidated. Laser-scanning confocal microscopy was used here to measure Ca2+ changes in the neuroblastoma x glioma hybrid cell line NG108-15, employed as a model nerve cell line, upon activation by the 5-HT3 receptor, a serotonin-activated ligand-gated ion channel. Addition of the 5-HT3 agonist 1-m-(chlorophenyl)-biguanide (mCPBG) induced increases in [Ca2+]i in both the cytoplasm and the nuclei of the NG108-15 cells. Using high-time resolution line scanning, no delay was evident between the mCPBG-induced rise in cytosolic [Ca2+]i and the rise in nuclear [Ca2+]i. The agonist-induced responses were completely blocked by addition of EGTA to chelate external Ca2+ and by addition of the 5-HT3 receptor antagonist tropisetron or the L-type Ca2+ channel blocker nitrendipine. Caffeine, but not thapsigargin, treatment significantly reduced the mCPBG-induced responses in the nucleus and the cytoplasm, both to the same extent. We conclude that, upon 5-HT3 receptor activation, Ca2+ enters the cells through voltage-gated Ca2+ channels and then triggers the release of Ca2+ from ryanodine-sensitive intracellular stores, greatly amplifying the increases in Ca2+ in the cytoplasm and the nucleus.
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PMID:5-HT3 receptors induce rises in cytosolic and nuclear calcium in NG108-15 cells via calcium-induced calcium release. 944 42

Different analgesic combinations with caffeine have shown this drug to be capable of increasing the analgesic effect. Many combinations with nonsteroidal anti-inflammatory drugs (NSAIDs) have been carried out, but, in regard to opioids, only combinations with morphine and tramadol have been reported. The antinociceptive synergism mechanism of these combinations is not well understood. The purpose of the present study was to determine the participation of spinal and supraspinal opioidergic and serotonergic systems in the synergic effect of the tramadol+caffeine combination in the rat formalin test. At the supraspinal level, the opioid antagonist, naloxone, completely reversed the effect of the drug combination, whereas ketanserin, a 5-HT2 receptor antagonist, inhibited the effect by 60%; however, ondansetron, a 5-HT3 receptor antagonist, did not alter the combination effect. When the antagonists were intrathecally administered, there was a significant reduction in all tramadol-caffeine combination effects. With respect to tramadol alone, there was significant participation of the opioid system at the supraspinal level, whereas it was the serotonergic system that participated at the spinal level by means of the two receptors studied. In conclusion, the tramadol+caffeine combination synergically activated the opioid and serotonergic systems at the supraspinal level, as well as at the spinal level, to produce the antinociception.
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PMID:Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms. 2614 27