• The Korean Journal of Physiology and Pharmacology
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• v.15 no.3
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• pp.129-135
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• 2011

In this study we determined whether or not 5-hydroxytryptamine (5-HT) has an effect on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of 5-HT on pacemaker activities were investigated using a whole-cell patch-clamp technique, intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) analysis, and RT-PCR in ICC. Exogenously-treated 5-HT showed tonic inward currents on pacemaker currents in ICC under the voltage-clamp mode in a dose-dependent manner. Based on RT-PCR results, we found the existence of 5-$HT_{2B,\;3,\;4,\;and\;7}$ receptors in ICC. However, SDZ 205557 (a 5-$HT_4$ receptor antagonist), SB 269970 (a 5-$HT_7$ receptor antagonist), 3-tropanylindole - 3 - carboxylate methiodide (3-TCM; a 5-$HT_3$ antagonist) blocked the 5-HT-induced action on pacemaker activity, but not SB 204741 (a 5-$HT_{2B}$ receptor antagonist). Based on $[Ca^{2+}]_i$ analysis, we found that 5-HT increased the intensity of $[Ca^{2+}]_i$. The treatment of PD 98059 or JNK II inhibitor blocked the 5-HT-induced action on pacemaker activity of ICC, but not SB 203580. In summary, these results suggest that 5-HT can modulate pacemaker activity through 5-$HT_{3,\;4,\;and\;7}$ receptors via $[Ca^{2+}]_i$ mobilization and regulation of mitogen-activated protein kinases.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.59-59
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• 2003

Serotonin (5-HT; 5-hydroxytryptamine) exerts multiple effects on central nervous system as well as behaviors such as mood and appetite. The signaling of serotonin is mediated by 7 families of serotonin receptors, designated 5-HT$_1$ to 5-HT$_{7}$. Six families of this receptor are G-protein coupled 7TM receptors, and the third intracellular loop of these receptors is proposed to interact with specific types of G-proteins. To investigate the specific interaction between the third intracellular loop of 5-HT$_{6}$ with G$\square$s, we have constructed a chimera protein that represent the third intracellular loop of 5-HT$_{6}$ within a leucine zipper motifs, In addition an alpha subunit of human G-protein that interact with 5-HT$_{6}$ was cloned into a bacterial expression vector. The two proteins were expressed in E. coli and purified in homogeneity. The interaction of the prepared proteins was examined by ELISA assay. The affinity between the two proteins and effect of insertion mutations were discussed.ussed.d.

• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.77-83
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• 1993

Serotonin (5-hydroxytryptamine, 5-HT) has been known to have peripheral actions as well as central actions. Recently physiological roles of 5-HT as a central neurotransmitter have been studied in detail and this is a subject of the present study. Plausible central actions mediated by 5-HT receptor seem to be a control of appetite, bring about psychiatric disorders such as anxiety or dementia, and migraine headache. In this study, thirty-five medicinal plants were tested for their antagonistic activities to 5-HT mediated actions. Through the preliminary screening, methanol extracts of three medicinal plants (Saussureae Radix, Sanguisorbae Radix and Xanthii Fructus) were shown to possess relatively specific antagonistic activities to 5-HT mediated ileal contraction over acetylcholine. To luther investigate the central antagonistic activities of the selected plant in vivo, m-chlorophenylpiperazine (mCPP) which is known to be a 5-H $T_{1c}$ receptor agonist was injected to mouse to induce an anxious and/or hypolocomotion states, and also social interaction test, which was based on the method described by File (S.E. File, 1980), was performed to see whether ethylacetate fraction of Sanguisorbae Radix methanol extract possessed a specific anxiolytic activity.y.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.6
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• pp.517-527
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• 2020

Layer 2/3 pyramidal neurons (L2/3 PyNs) of the cortex extend their basal dendrites near the soma and as apical dendritic tufts in layer 1, which mainly receive feedforward and feedback inputs, respectively. It is suggested that neuromodulators such as serotonin and acetylcholine may regulate the information flow between brain structures depending on the brain state. However, little is known about the dendritic compartment-specific induction of synaptic transmission in single PyNs. Here, we studied layer-specific serotonergic and cholinergic induction of long-term synaptic plasticity in L2/3 PyNs of the agranular insular cortex, a lateral component of the orbitofrontal cortex. Using FM1-43 dye unloading, we verified that local electrical stimulation to layers 1 (L1) and 3 (L3) activated axon terminals mostly located in L1 and perisomatic area (L2/3). Independent and AMPA receptor-mediated excitatory postsynaptic potential was evoked by local electrical stimulation of either L1 or L3. Application of serotonin (5-HT, 10 μM) induced activity-dependent longterm depression (LTD) in L2/3 but not in L1 inputs. LTD induced by 5-HT was blocked by the 5-HT₂ receptor antagonist ketanserin, an NMDA receptor antagonist and by intracellular Ca²⁺ chelation. The 5-HT₂ receptor agonist α-me-5-HT mimicked the LTD induced by 5-HT. However, the application of carbachol induced muscarinic receptor-dependent LTD in both inputs. The differential layer-specific induction of LTD by neuromodulators might play an important role in information processing mechanism of the prefrontal cortex.

• Molecules and Cells
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• v.20 no.1
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• pp.69-73
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• 2005

The flavonoid, quercetin, is a low molecular weight substance found in apple, tomato and other fruit. Besides its antioxidative effect, quercetin, like other flavonoids, has a wide range of neuropharmacological actions including analgesia, and motility, sleep, anticonvulsant, sedative and anxiolytic effects. In the present study, we investigated its effect on mouse 5-hydroxytryptamine type 3 ($5-HT_{3A}$) receptor channel activity, which is involved in pain transmission, analgesia, vomiting, and mood disorders. The $5-HT_{3A}$ receptor was expressed in Xenopus oocytes, and the current was measured with the two-electrode voltage clamp technique. In oocytes injected with $5-HT_{3A}$ receptor cRNA, quercetin inhibited the 5-HT-induced inward peak current ($I_{5-HT}$) with an $IC_{50}$ of $64.7{\pm}2.2{\mu}M$. Inhibition was competitive and voltage-independent. Point mutations of pre-transmembrane domain 1 (pre-TM1) such as R222T and R222A, but not R222D, R222E and R222K, abolished inhibition, indicating that quercetin interacts with the pre-TM1 of the $5-HT_{3A}$ receptor.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.6
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• pp.295-301
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• 2003

Striatum plays a crucial role in the movement control and habitual learning. It receives an information from wide area of cerebral cortex as well as an extensive serotonergic (5-hydroxytryptamine, 5-HT) input from raphe nuclei. In the present study, the effects of 5-HT to modulate synaptic transmission were studied in the rat corticostriatal brain slice using in vitro extracellular recording technique. Synaptic responses were evoked by stimulation of cortical glutamatergic inputs on the corpus callosum and recorded in the dorsal striatum. 5-HT reversibly inhibited coticostriatal glutamatergic synaptic transmission in a dose-dependent fashion (5, 10, 50, and $10{\mu}M$), maximally reducing in the corticostriatal population spike (PS) amplitude to $40.1{\pm}5.0$% at a concentration of $50{\mu}M$ 5-HT. PSs mediated by non-NMDA glutamate receptors, which were isolated by bath application of the NMDA receptor antagonist, d,l-2-amino-5-phospohonovaleric acid (AP-V), were decreased by application of $50{\mu}M$ 5-HT. However, PSs mediated by NMDA receptors, that were activated by application of zero $Mg^{2+}$ aCSF, were not significantly affected by $50{\mu}M$ 5-HT. To test whether the corticostriatal synaptic inhibitions by 5-HT might involve a change in the probability of neurotransmitter release from presynaptic nerve terminals, we measured the paired-pulse ratio (PPR) evoked by 2 identical pulses (50 ms interpulse interval), and found that PPR was increased ($33.4{\pm}5.2$%) by 5-HT, reflecting decreased neurotransmitter releasing probability. These results suggest that 5-HT may decrease neurotransmitter release probability of glutamatergic corticostriatal synapse and may be able to selectively decrease non-NMDA glutamate receptor-mediated synaptic transmission.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.4
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• pp.247-254
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• 2018

A This study evaluated the antidepressant effects of the herbal mixture CPAE(Cynanchum wilfordii Hemsley, Phlomis umbrosa Turcz, and Angelica gigas Nakai) using several tests, including a test for serotonin 6($5-HT_6$) receptor activity, the forced swimming test(FST), and tests for corticosterone(CORT) and monoamine levels. CPAE showed antagonistic effects on the $5-HT_6$ receptor in a stable $5-HT_6$ receptor-expressing cell line. We subsequently confirmed the antidepressant effects of CPAE in chronic stress model in mice and explored the underlying mechanisms of its action. Specifically, we observed that CPAE treatment significantly reduced immobility time in the FST and effectively restored abnormal levels of CORT in plasma and of monoamines(serotonin, dopamine, and norepinephrine) in hippocampus and prefrontal cortex. These results suggest that CPAE has significant antidepressant effects.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.347-353
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• 2000

It has been well documented that a massive release of not only glutamate but also other neurotransmitters may modulate the final responses of nerve cells to the ischemic neuronal injury. But there is no information regarding whether the release of monoamines is directly associated with synaptic vesicular proteins under ischemia. In the present study, it was investigated whether synapsin 1, syntaxin and SNAP-25 are involved in the release of 5-hydroxytryptamine $([^3H]5-HT)$ in glucose/oxygen deprived (GOD) rat hippocampal slices. And, the effect of NMDA receptor using DL-2-amino-5-phosphonovaleric acid (APV) on ischemia- induced release of 5-HT and the changes of the above proteins were also investigated. GOD for 20 minutes enhanced release of $[^3H]5-HT,$ which was in part blocked by the NMDA receptor antagonist, APV. The augmented expression of synapsin 1 during GOD for 20 minutes, which was also in part prevented by APV. In contrast, the expression of syntaxin and SNAP-25 were not altered during GOD. These results suggest that ischemic insult induces release of $[^3H]5-HT$ associated with synapsin 1, synaptic vesicular protein, via activation of NMDA receptor in part.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.65-70
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• 2012

Synaptic long-term potentiation (LTP) and long-term depression (LTD) have been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. Serotonin (5-hydroxytryptamine, 5-HT) inhibits the induction of LTP and LTD during the critical period of the rat visual cortex (postnatal 3~5 weeks). However, in adult rats, the increase in 5-HT level in the brain by the administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine reinstates ocular dominance plasticity and LTP in the visual cortex. Here, we investigated the effect of 5-HT on the induction of LTP in the visual cortex obtained from 3- to 10-week-old rats. Field potentials in layer 2/3, evoked by the stimulation of underlying layer 4, was potentiated by theta-burst stimulation (TBS) in 3- and 5-weekold rats, then declined to the baseline level with aging to 10 weeks. Whereas 5-HT inhibited the induction of LTP in 5-week-old rats, it reinstated the induction of N-methyl-D-aspartate receptor (NMDA)-dependent LTP in 8- and 10-week-old rats. Moreover, the selective SSRI citalopram reinstated LTP. The potentiating effect of 5-HT at 8 weeks of age was mediated by the activation of 5-$HT_2$ receptors, but not by the activation of either 5-$HT_{1A}$ or 5-$HT_3$ receptors. These results suggested that the effect of 5-HT on the induction of LTP switches from inhibitory in young rats to facilitatory in adult rats.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.605-611
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• 2016

Ketamine is an anesthetic with hypertensive effects, which make it useful for patients at risk of shock. However, previous ex vivo studies reported vasodilatory actions of ketamine in isolated arteries. In this study, we reexamined the effects of ketamine on arterial tones in the presence and absence of physiological concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) by measuring the isometric tension of endothelium-denuded rat mesenteric arterial rings. Ketamine little affected the resting tone of control mesenteric arterial rings, but, in the presence of 5-HT (100~200 nM), ketamine ($10{\sim}100{\mu}M$) markedly contracted the arterial rings. Ketamine did not contract arterial rings in the presence of NE (10 nM), indicating that the vasoconstrictive action of ketamine is 5-HT-dependent. The concentration-response curves (CRCs) of 5-HT were clearly shifted to the left in the presence of ketamine ($30{\mu}M$), whereas the CRCs of NE were little affected by ketamine. The left shift of the 5-HT CRCs caused by ketamine was reversed with ketanserin, a competitive 5-$HT_{2A}$ receptor inhibitor, indicating that ketamine facilitated the activation of 5-$HT_{2A}$ receptors. Anpirtoline and BW723C86, selective agonists of 5-$HT_{1B}$ and 5-$HT_{2B}$ receptors, respectively, did not contract arterial rings in the absence or presence of ketamine. These results indicate that ketamine specifically enhances 5-$HT_{2A}$ receptor-mediated vasoconstriction and that it is vasoconstrictive in a clinical setting. The facilitative action of ketamine on 5-$HT_{2A}$ receptors should be considered in ketamine-induced hypertension as well as in the pathogenesis of diseases such as schizophrenia, wherein experimental animal models are frequently generated using ketamine.