• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.1-9
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• 1995

The slow development of histopathological changes and long period required for stabilization of lesions have suggested that secondary injury processes exacerbate the effect of initial mechanical insult after traumatic spinal cord injury (SCI). The importance of glutamate receptors in the normal functions of spinal cord, in concert with the large body of evidence that points to their involvement in neurotoxicity due to both ischemic and traumatic insults to the CNS, suggested a probable role of glutamate receptors in secondary injury process after traumatic SCI. In order to investigate the involvement of excitatory amino acid in the secondary injury process after SCI, this study examined the effect of dextrorphan, a noncompetitive NMDA receptor antagonist, on the recovery of hindlimb function and the residual tissue at injury site following SCI. Locomotor function was assessed using open field test (21 point scale). At 8 weeks spinal cord tissue was examined using quantitative histopathologic technique. Prior to surgery female Long-Evans rats were adapted to the test environment. Rats received laminectomies (T9/T10), and spinal cord contusions (NYU impactor) were produced by a 10 gm weight dropped 25 mm. DXT (15 or 30 mg/kg, i.p.) or saline was injected 15 min before contusion. Behavioral testing resumed 2 days post-injury and continued twice a week for 8 weeks. No differences between DXT and saline groups were found for hindlimb function and sparing tissue at the lesion site. These results suggest that NMDA receptor might not be involved in secondary injury processes after traumatic SCI.

• Applied Biological Chemistry
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• v.39 no.3
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• pp.189-194
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• 1996

The effects of scorpion (Leiurus quinquestriatus hebraeus, Lqh) venom were evaluated on the activities of microsomal $Ca^{2+}-ATPase$ and $Ca^{2+}$ release channel prepared from the epithelial cells of pig airway. Whole venom of Lqh $(120\;{\mu}g/ml)$ increased the activity of microsomal $Ca^{2+}-ATPase$ about 32% in the tight-sealed microsomes and about 28% in the Triton X-100-treated or $Ca^{2+}$ ionophore A23187-treated leaky microsomes. Thapsigargin, a specific antagonist of $Ca^{2+}-ATPase$, inhibited 42% of total ATPase activity and also completely blocked the effects of Lqh venom, suggesting that Lqh venom directly activiates the microsomal $Ca^{2+}-ATPase$. In order to determine if Lqh venom increases the microsomal uptake of $^{45}Ca^{2+}$, Lqh venom was added in the uptake medium. The Lqh venom increased microsomal $^{45}Ca^{2+}$ uptake up to ${\sim}20%$ and the increase was only observed when heparin, an antagonist of $InsP_3$ receptor channel, was added in the uptake medium. Lqh venom in the absence of heparin unexpectedly decreased the rate and the amount of $^{45}Ca^{2+}$ uptake. These results were explained by simultaneous increases in $^{45}Ca^{2+}$ release as well as $^{45}Ca^{2+}$ uptake by Lqh venom. Lqh venom itself increased the release of $^{45}Ca^{2+}$ as much as $^{45}Ca^{2+}$ release by $4\;{\mu}m\;InsP_3$, implying that Lqh venom also activates $InsP_3$ receptor, microsomal $Ca^{2+}$ release channel. Based on these results, we suggest that the Lqh venom consists of at least two components; one activates the $InsP_3$ receptor and the other avates the $Ca^{2+}-ATPase$. Currently we a investigating the chemical and electrophysiological properties of the active components of Lqh venom.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.389-396
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• 2002

In the present work, we examined the mechanism of vasorelaxant effect of scopoletin, an active constituent of Artemisia capillaris on rat thoracic descending aortic rings. Scopoletin induced a concentration-dependent relaxation in rat thoracic descending aortic rings pre-contracted with phenylephrine (EC/sub 50/ = 238.94±37.4 μM), while it was less effective in rat thoracic descending aortic rings precontracted with high potassium solution (KCI 30 mM). Vasorelaxation by scopoletin was significantly inhibited after endothelial removal, but recovered at high concentration. Pretreatment of rat thoracic descending aortic rings with N/sup G/-nitro-L-arginine (100 μM), a nitric oxide synthase inhibitor, and atropine (1 μM), a muscarinic receptor antagonist, significantly inhibited scopoletin-induced relaxation of rat thoracic descending aortic rings. Neither indomethacin (3 μM), an inhibitor of cydooxygenase, nor propranolol (1 μM), a β -adrenoceptor antagonist, modified the effect of scopoletin. The combination of N/sup G/ -nitro-L-arginine (100 μ M) and miconazole (10 μ M), an inhibitor of cytochrome P 450, did not modify the effect of scopoletin, when compared with pretreatment with N/sup G/-nitro-L-arginine(100 μM) alone. Vasorelaxant effect of scopoletin was inverted by pretreatment with diltiazem (10 μM), a Ca/sup 2+/-channel blocker, at low concentration, while restored at high concentration. Apamin (K/sub ca/-channel blocker, 1 μM), 4-aminopyridine (4-AP, K/sub v/-channel blocker, 1 mM), and tetrodotoxin (TTX, Na/sup +/-channel blocker 1 μM) potentiated the vasorelaxant effect of scopoledn, but glibendamide (K/sub ATP/-channel blocker, 10 μM), tetraetylammonium(TEA, non-selective K-channel blocker, 10 mM) did not affect the relaxation of scopoletin. Free radical scavengers (TEMPO, catalase, mannitol) did not modify vascular tone. These results suggest that nitric oxide, Ca/sup 2+/ -channels play a role in endothelium-dependent relaxations to scopoletin in rat aortas, that apamin, 4-AP, TTX but not glibenclamide, TEA potentiated relaxation to scopoletin mediated by these channels, and that free radicals do not concern to the vasorelaxant effect of scopoletin.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.699-705
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• 1997

Although it is known that neuronal cell death during development occurs by apoptosis, the mechanisms underlying excitatory amino acid-induced neuronal cell death remain poorly understood. In this study we have examined the mechanism by which L-glutamate, an excitatory amino acid neurotransmitter, induces cell death in PC12 cell lines. To characterize cell death, we employed sandwich enzyme-linked immunosorbent assay(ELISA) method for cellular DNA fragmentation, DNA agarose gel electrophoresis and chromatin staining by acridine orange and ethidium bromide after treating the PC12 cells with L-glutamate. L-Glutamate caused dose-dependent cell death with a maximum at 24 hrs after the treatment. These cellular fragmentation was blocked by pretreatment of MK-801, a noncompetitive N-methyl-D-aspartic acid(NMDA) receptor antagonist, and nerve growth factor(NGF). Analysis of DNA integrity from L-glutamate-treated cells revealed cleavage of DNA into regular sized fragments, a biochemical hallmark of apoptosis. The PC12 cells that were induced to die by L-glutamate treatment exhibited classical chromatin condensation under the light microscopy after acridine orange and ethidium bromide staining. These results suggest that apoptosis is one of the key features that are involved in L-glutamate-induced excitotoxic cell death in PC12 cells, and these cell death are mediated by NMDA receptor and depend on NGF.

• 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.

• The Korean Journal of Pharmacology
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• v.21 no.2
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• pp.99-110
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• 1985

Majarine that was isolated from Berberis Koreasra Palibin (Berberidaceae) is the isoquinoline alkaloid. The effects of dopaminergic and serotonergic antagonists on majarine induced changes in body temperature were studied in the mouse. Intraperitoneal administration of majarine produced dose-dependent hypothermia. At a dose of 0.1 mg/kg, majarine caused a slight increase in body temperature. Majarine-induced hyperthermia was attenuated by the 5-HT antagonist, cyproheptadine However, it caused hyothermia in mice pretreated with the DA antagonist, haloperidol, and hyperthermia in mice pretreated with haloperidol and cyproheptadine in comparision with haloperidol pretreatment. At a dose of 2.0 mg/kg, majarine-induced hypothermia was attenuated by haloperidol and cyproheptadine, respectively. In reserpine pretreated mice, majarine produced dose-dependent hypothermia. At a dose of 0.1 mg/kg, majarine pretreated with haloperidol caused no significant effect in body temperature. At a dose of 2.0 mg/kg, majarine-induced hypothermia was attenuated by haloperidol pretreatment in mice treated with reserpine and ${\alpha}$-methyl-p-tyrosine. These data suppose that both dopaminergic and serotonergic mechanisms in the brain mediate the effects of majarine on body temperature. We propose that majarine directly stimulate DA receptor, which secondarilly activate 5-HT neurons to cause changes in body temperature.

• The Korean Journal of Zoology
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• v.34 no.3
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• pp.426-431
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• 1991

The present study examines the effect of naloxone, mu-opioid receptor antagonist, on prolactin (PRL) gene expression and secretion induced by estradiol (I) treahent in vivo. Adult rats were ovariectomized (OW) and implanted with Silastic capsules containing either vehicle (oil) or E. Three days later, NAL (2 mg/kg BW) or saline urere injected 30 min prior to sacrifice. To examine PRL secretion in vitro, the pituitaries were incubated in the superfusion system for 3 hrs. Superfusates were collected at 10 min intenrals on ice and subjected to PRL radioimmunoassay. Endogenous release of PRL in OU( + I rats was signifcantlv higher than that in OVX rats (mean $\pm$ SE; 24.5 $\pm$ 3.1 vs 14.5 $\pm$ 2.9 ns/10 min). A single injection of NAL clearly inhibited PRL release in Nitro from pituitaries derived from OW + I rats, but not from OW group. PRL myNA was determined by RNA-blot hybridisation assay with nicktranslated PRL CDNA. E stimulated PRL mRNA about 3 fold over that shown in OW group. Treahent of NAL suppressed the I-stimulated PRL myNA in OVX + I group, but not in OVX group. These data clearly showed that the NAL-induced inhibition of PRL secretion was well correlated with changes in PRL mRNA level and this inhibitory process appears to be mediated in I-dependent manner.

• The Korean Journal of Pain
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• v.13 no.1
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• pp.31-37
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• 2000

Background: Recent studies suggested that a preoperative block of N-methyl-D-aspartate (NMDA) receptors with NMDA antagonists may reduce postoperative pain. In this double-blind study, magnesium sulfate, a natural NMDA receptor antagonist, was administered preoperatively to investigate the effects of magnesium sulfate on postoperative pain and pulmonary function. Methods: Seventy patients who were to undergo gastrectomy under general anesthesia were randomly assigned to one of three groups. Groups 2 and 3 received intravenous magnesium, preoperatively (Group 2: 50 mg/kg bolus, 7.5 mg/kg/hr for 20 hr, Group 3: 50 mg/kg bolus, 15 mg/kg/hr for 20 hr). Group 1 received normal saline as the control group. Visual analog scale (VAS) for postoperative pain and mood, cumulative analgesic consumption, recovery of pulmonary function and side effects were evaluated at 6, 24, 48 and 72 hours after the operation. Results: In Groups 2 and 3, plasma concentration of magnesium were significantly higher than in Group 1 at 6 and 20 hours after infusion (P<0.05). There were no significant differences in the analgesic consumption, and recovery of pulmonary function and the incidence of side effects at 6, 24, 48 and 72 hours after the operation among the three groups. In Group 3, pain scores at rest measured 24 and 48 hours after operation were lower than the control group, and pain scores when deep breathing were significantly lower than the control group at postoperative 6, 24, 48, and 72 hours. Conclusions: We conclude that intravenous infusion of greater amount of magnesium has little effectiveness in reducing postoperative pain. However, further studies are needed to characterize the clinical significance of these effects on postoperative pain.

• Korean Journal of Acupuncture
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• v.30 no.4
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• pp.220-229
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• 2013

Objectives : Electroacupuncture(EA) has been used effectively in producing analgesia on ankle sprain pain of humans and animals. Currently to examine the underlying mechanisms of the EA-induced analgesia, the effects of EA on weight-bearing forces(WBR) were examined at ankle sprain classified as grade 3 in rats. Methods : The severe ankle sprain classified as grade 3 was induced surgically by ankle ligament injury in the Sprague-Dawley rats. WBR of the affected foot were examined to evaluate effects and mechanism of EA(2 Hz, 1 ms pulse width, 2 mA intensity, for 15 min) which was applied to either SI6, GB34, or GB39 acupoints. The rats were pretreated with naltrexone(10 mg/kg, i.p.) as an opioid receptor antagonist or phentolamine(5 mg/kg, i.p) as an ${\alpha}$-adrenoceptor antagonist at 30 min before EA. Results : The daily repeat EA at either SI6, GB34, or GB39 showed significant analgesic effects on the severe ankle sprain. Particularly, daily EA at GB34 showed more potent analgesic effect than the others. In addition, the naltrexone pretreatment completely blocked the analgesic effect of EA at GB34, indicating the involvement of the endogenous opioid system in mediating the effect of EA at GB34. However, the phentolamine pretreament blocked analgesic effects of EA at either SI6 or GB39, indicating the involvement of ${\alpha}$-adrenoceptors in mediating the effect of EA at either SI6 or GB39. Conclusions : These data suggest that EA-induced analgesia on ankle sprain pain is mediated through either endogenous opioids or ${\alpha}$-adrenoceptors dependant on acupoint specific pattern.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.1
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• pp.45-53
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• 2005

The present study was designed to examine the effect of d-amphetamine on CA release from the isolated perfused model of the rat adrenal gland, and to establish its mechanism of action. Damphetamine $(10{\sim}100{\mu}M$), when perfused into an adrenal vein of the rat adrenal gland for 60 min, enhanced the CA secretory responses evoked by ACh ($5.32{\times}10^{-3}$ M), excess $K^+$ ($5.6{\times}10^{-2}$ M, a membrane depolarizer), DMPP ($10^{-4}$ M, a selective neuronal nicotinic $N_n-receptor$ agonist) and McN-A-343 ($10^{-4}$ M, a selective $M_1-muscarinic$ agonist) only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, d-amphetamine ($30{\mu}M$) in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type $Ca^{2+}$ channels, and cyclopiazonic acid, an inhibitor of cytoplasmic $Ca^{2+}$ ATPase only for the first period (4 min). However, in the presence of high concentration ($500{\mu}M$), d-amphetamine rather inhibited the CA secretory responses evoked by the above all of secretagogues. Collectively, these experimental results suggest that d-amphetamine at low concentrations enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization, but at high concentration it rather inhibits them. It seems that d-amphetamine has dual effects as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which might be dependent on the concentration. It is also thought that these actions of d-amphetamine are probably relevant to the $Ca^{2+}$ mobilization through the dihydropyridine L-type $Ca^{2+}$ cha$N_n$els located on the rat adrenomedullary chromaffin cell membrane and the release of $Ca^{2+}$ from the cytoplasmic store.