• Biomolecules & Therapeutics
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• 제4권1호
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• pp.7-18
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• 1996

5-Hydroxytryptamine(5-HT, serotonin), when given into the vein, produced antidiuretic action accompanied with reduction of glomerular filtration(GFR), renal plasma flow(RPF), osmolar clearance(Cosm) and amounts of sodium or potassium excreted in urine( $E_{Na}$ , $E_{K}$), with the augmented reabsorption rates of sodium and potassium in renal tubules. 5-HT, when infused into a renal artery, exhibited diuretic action accompanied with the augmented RPF and increased $E_{Na}$ and $E_{K}$ in only infused kidney. Antidiuretic action of 5-HT infused into the vein was not influenced by ketanserin, 5-H $T_2$receptor blockade, given into a renal artery, vein or carotid artery, by methysergide, 5-H $T_1$receptor blockade, given into a renal artery, whereas above antidiuretic action was inhibited by methysergide given into vein or carotid artery. Diuretic action of 5-HT infused into a renal artery in only experimental kidney was blocked by ketanserin injected into a renal artery, was not influenced by methysergide administered into a renal artery. Above results suggest that 5-hydroxytryptamine(5-HT) produced the antidiuretic action through central 5-H $T_1$receptor and the diuretic action through 5-H $T_2$receptor located in renal tubules of kidney.ney.

• 통합자연과학논문집
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• 제11권2호
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• pp.87-92
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• 2018

5-Hydroxytryptamine receptor 7 ($5-HT_7R$) is one of G-Protein coupled receptors, which is found to be involved in the pathophysiology of various neurological disorders including depression, sleep disorders, memory deficiency and neuropathic pain. After activation of $5-HT_7R$ by serotonin, it activates the production of the intracellular signaling molecule cyclic AMP. The availability of 3D structure of the receptor would enhance the development of new drugs. Hence, in the present study, homology modelling of human 5-hydroxytryptamine receptor 7 ($5-HT_7R$) was performed using comparative modelling (Easy Modeller) and threading (I-TASSER) approaches. The generated models were validated using Ramachandran plot and ERRAT plot and the best models were selected based on the validation results. The 3D model developed here could be useful for identifying crucial residues and further docking study.

• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.419-426
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• 2019

Mosapride accelerates gastric emptying by acting on 5-hydroxytryptamine type 4 ($5-HT_4$) receptor and is frequently used in the treatment of gastrointestinal (GI) disorders requiring gastroprokinetic efficacy. We tested the effect of mosapride on 5-hydroxytryptamine type 3 ($5-HT_3$) receptor currents because the $5-HT_3$ receptors are also known to be expressed in the GI system and have an important role in the regulation of GI functions. Using the whole-cell voltage clamp method, we compared the currents of the $5-HT_3$ receptors when 5-HT was applied alone or was co-applied with mosapride in cultured NCB-20 cells known to express $5-HT_3$ receptors. The $5-HT_3$ receptor current amplitudes were inhibited by mosapride in a concentration-dependent manner. Mosapride blocked the peak currents evoked by the application of 5-HT in a competitive manner because the $EC_{50}$ shifted to the right without changing the maximal effect. The rise slopes of $5-HT_3$ receptor currents were decreased by mosapride. Pre-application of mosapride before co-application, augmented the inhibitory effect of mosapride, which suggests a closed channel blocking mechanism. Mosapride also blocked the opened $5-HT_3$ receptor because it inhibited the $5-HT_3$ receptor current in the middle of the application of 5-HT. It accelerated desensitization of the $5-HT_3$ receptor but did not change the recovery process from the receptor desensitization. There were no voltage-, or use-dependency in its blocking effects. These results suggest that mosapride inhibited the $5-HT_3$ receptor through a competitive blocking mechanism probably by binding to the receptor in closed state, which could be involved in the pharmacological effects of mosapride to treat GI disorders.

• Toxicological Research
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• 제14권4호
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• pp.483-488
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• 1998

During cerebral ischemia two important factors such as hypoxia and reduction of glucose can act as modulating stressor affecting the release of amine neurotransmitters including 5-hydroxytryptamine (5-HT). This study was performed to investigate the effect of glucose deprivation on the oxygen deprivation-induced changes of [3H]-5-HT release in the rat hippocampal slices. Experimental groups were divided into 4 groups for this study: normoxic/normoglycemic group, oxygen-deprived group, glucose-deprived group, and oxygen/glucose-deprived group. The hippocampus of rat brain was sliced by 400 $\mu\textrm{m}$ thickness with manual chopper. After 30 minutes preincubation in the normal buffer, the slices were incubated for 20 min in buffer containing [3H]-5-HT (0.1 M, 74 $\mu\textrm$Ci) for uptake. To measure the release of [3H]-5-HT into the buffer, the incubation medium was drained of and refilled with fresh buffer every ten minutes through a sequence of 14 tubes. Oxygen deprivation by gassing with 95% $N_2$/5% $CO_2$ and/or glucose deprivation was done in the 6th and 7th tube. The radioactivities in each buffer and the tissue were counted using scintillation counter. The results were expressed as fractional release. When slices were exposed to oxygen-deprived media for 20 min, the diminution followed by the rebound release of [3H]-5-HT was observed during the post-oxygen deprived period. However, glucose deprivation or oxygen/glucose deprivation markedly increased the release of [3H]-5-HT. which was opposite to the pattern observed in oxygen-deprived group. These results suggested that oxygen deprivation itself inhibits [3H]-5-HT release in rat hippocampal slices during oxygen-deprived period, but additional glucose deprivation convert the inhibitory response to increase of [3H]-5-HT release.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.657-664
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• 1997

The effects of adenosine, adenosine A1 receptor antagonist (DPCPX), or NMDA receptor antagonist (APV) on the spontaneous release of $[^3H]-5-hydroxytryptamine$ ($[^3H]-5-HT$) during normoxic/normoglycemic or hypoxic/hypoglycemic period were studied in the rat hippocampal slices. The hippocampus was obtained from the rat brain and sliced $400\;{\mu}m$ thickness with the tissue slicer. After 30 min's preincubation in the normal buffer, the slices were incubated for 30 min in a buffer containing $[^3H]-5-HT$ ($0.1\;{\mu}M,\;74{\mu}Ci/8\;ml$) for uptake, and washed. To measure the release of $[^3H]-5-HT$ into the buffer, the incubation medium was drained off and refilled every ten minutes through sequence of 14 tubes. Induction of glucose/oxygen deprivation (GOD; medium depleting glucose and gassed with 95% $N_2/5%\;CO_2$) was done in 6th and 7th tube. The radioactivities in each buffer and the tissue were counted using liquid scintillation counter and the results were expressed as a percentage of the total radioactivities. When slices were exposed to GOD for 20 mins, the spontaneous release of $[^3H]-5-HT$ was markedly increased and this increase of $[^3H]-5-HT$ release was blocked by adenosine ($10\;{\mu}M$) or DL-2-amino-5-phosphonovaleric acid (APV; $30\;{\mu}M$). Adenosine $A_1$ receptor specific antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) exacerbate GOD-induced increase of spontaneous release of $[^3H]-5-HT$. These results suggest that Adenosine may play a role in the GOD-induced spontaneous release of $[^3H]-5-HT$ through adenosine $A_1$ receptor activity.

• The Korean Journal of Physiology and Pharmacology
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• 제7권6호
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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.

• Archives of Pharmacal Research
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• 제22권2호
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• pp.113-118
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• 1999

Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic $5-HT_{2}$ receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompeti-tive (MI-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsyaptic $5-HT_{2}$receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin $5-HT_{2}$receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the poststynaptic $5-HT_{2}$ receptors.

• The Korean Journal of Physiology and Pharmacology
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• 제4권5호
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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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• 제11권5호
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• pp.221-226
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• 2007

Melittin-induced tonic pain model is characterized by local inflammation, edema, spontaneous flinchings, and sustained mechanical hypersensitivity. These nociceptive responses are mediated through selective activation of capsaicin-sensitive primary afferent fibers by melittin. The present study was undertaken to elucidate the role of peripheral 5-hydroxytryptamine(5-HT) receptors in the melittin-induced nociceptive responses. Changes in mechanical threshold, flinching behaviors and paw thickness were measured in rat intraplantarly injected with melittin($40{\mu}g/paw$) alone or treated together with melittin and 5-HT receptor antagonists. WAY-100635($100{\mu}g\;&\;200{\mu}g/paw$), isamoltane hemifumarate($100{\mu}g\;&\;200{\mu}g/paw$), methysergide maleate($60{\mu}g,\;120{\mu}g\;&\;200{\mu}g/paw$) and ICS-205,930($100{\mu}g\;&\;200{\mu}g/paw$) were intraplantarly injected 20 min before melittin injection. All 5-HT receptor antagonists tested in this experiment significantly attenuated the ability of melittin to reduce mechanical threshold and to induce flinching behaviors. 5-HT receptor antagonists, except ICS-205,930, had mild inhibitory effect on melittin-induced edema. These experimental findings suggest that multiple peripheral 5-HT receptors are involved in the melittin-induced nociceptive responses.

• The Korean Journal of Physiology and Pharmacology
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• 제15권5호
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• pp.267-272
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• 2011

A number of studies have demonstrated that 5-hydroxytryptamine (5-HT) can induce muscle contraction or relaxation response and enhance secretion in the gastrointestinal tract via a multiplicity of 5-HT receptor subtypes. In the present study, we investigated the pharmacological characterization of the 5-HT-induced contractile response in longitudinal smooth muscle isolated from the feline ileum. Addition of 5-HT into muscle chambers enhanced the basal tone and spontaneous activity in a concentration-dependent manner. The neurotoxin tetrodotoxin did not alter the 5-HT-induced contraction of the longitudinal muscles. Neither atropine nor guanethidine affected the contraction. The 5-HT agonists, 5-methylserotonin hydrochloride and mosapride, also evoked concentration-dependent contractions. The 5-HT-induced contraction was enhanced by the $5HT_2$ receptor antagonist ketanserin and the $5-HT_3$ receptor antagonist ondansetron but was inhibited by the 5-$HT_1$ receptor antagonist methysergide and 5-$HT_4$ receptor antagonist GR113808. These results indicate that 5-$HT_1$ and 5-$HT_4$ receptors may mediate the contraction of the 5-HT-induced response and 5-$HT_2$ and 5-$HT_3$ receptors may mediate 5-HT-induced relaxation in feline ileal longitudinal smooth muscles.