• 대한한방내과학회지
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• 제27권2호
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• pp.471-479
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• 2006

Backgrounds & Objectives: Banhasasimtang granule(BHSST) has been used for the treatment of functional dyspepsia regarded as one of the gastric dysmotility disease. but its mechanisms of action are not well known yet: So we investigated the effects of BHSST on gastric emptying and its mechanisms of action in rats. Methods: Gastric emptying was measured by glass beads(1mm in diameter) expelled from the stomach for 60 min after administration of normal saline(NS) or BHSST 31mg/kg or 93mg/kg in rats. And by the same method gastric emptying was measured after administration of NS or BHSST 93mg/kg in rats treated with atropine sulfate(1mg/kg, s.c.), quinpirol HCI(0.3mg/kg, i.p.), NAME(NG-nitro-L-arginine methyl ester, 75mg/kg, s.c.) or cisplatin(10mg/kg, i.p.) to make delayed gastric emptying. Results: BHSST 93mg/kg improved gastric emptying more than NS or BHSST 31mg/kg(p=0.016). Under the delayed gastric emptying, BHSST 93mg/kg improved gastric emptying in the group treated with NAME$(5.00{\pm}3.101\;vs\;9.00{\pm}3.51,\;p\;=0.046)$, but aggravated it With atropine sulfate$(5.71{\pm}3.45\;vs\;2.57{\pm}1.62,\;p\;=0.050)$ and cisplatin$(12.7{\pm}2.29\;vs\;8.57{\pm}5.06,\;p\;=0.072)$. Conclusions: BHSST improves the gastric emptying through cholinergic and 5-hydroxytryptamine 3 receptors. Especially it is effective to improve gastric emptying delayed by NAME. So we expect that it would be effective in functional dyspepsia with impaired reservoir functions such as gastric adaptive relaxation.

• 대한한방내과학회지
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• 제28권2호
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• pp.242-249
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• 2007

Backgrounds & Objectives : Yukgunjatanggranule (YGJT) ha been used for the treatment of functional dyspepsia, regarded as one of the gastric dysmotility diseases, but its mechanisms of cation are not yet well known, We investigated the effects of YGJT on gastric emptying and its mechanisms of action in rats. Methods : Gastric emptying was measured by glass beads (1mm in diameter) expelled from the stomach for 1 hour and 2 hours after administration ofnormal saline (NS) or YGJT 41.6mg/kg or 124.8mg/kg in rats. By the same method, gastric emptying was measured only for 2 hours after administration of NS of YGJT 124.8mg/kg in rats treated with atropine sulfate (1mg/kg, s.c), quinpirole HCl(0.3mg/kg, i.p.), NAME (NG-nitro-L-arginine methyl ester, 75mg/kg, s.c.) or cisplatin (10mg/kg, i.p.) to delay gastric emptying. Results : YGJT 124.8mg/kg improved gastric emptying more than NS or YGJT 41.6mg/kg (p=0.046). Under delayed gastric emptying, YGJT 124.8mg/kg improved gastric emptying in the group treated with cisplatin ($3.1{\pm}1.3$ vs. $6.6{\pm}3.1$, p=0.015), quinpirole HCl ($4.7{\pm}2.8$ vs. $5.5{\pm}5.6$, p=0.874) and NAME ($2.2{\pm}1.4$ vs. $4.7{\pm}6.0$, p=0.414), but aggravated it with atropine sulfate ($1.8{\pm}0.9$vs. $1.7{\pm}1.0$, p=0.957). Conclusions : YGJT improves gastric emptying through the cholinergic pathwas, and shows some effect against the toxicity of cisplatin. Therefore, we expect that it would be effective in relieving gastrointestinal symptoms in functional dyspepsia patients and cisplatin-treated patients.

• 대한한방내과학회지
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• 제29권1호
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• pp.189-199
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• 2008

Background & Objective : Jichul-hwan(JCH) has been used for the treatment of functional dyspepsia, regarded as a gastric dysmotility disease. We investigated the effects of JCH on gastric motility and its mechanisms of action in rats. Methods : The gastric wall was injured by tracting a part of stomach body in rats. Gastric emptying was measured after administration of normal saline(NS) or JCH in normal rats and gastric wall injured rats. To evaluate the mechanism of JCH under delayed gastric emptying conditions, normal rats were treated with atropine sulfate(1mg/kg, s.c.), quinpirole HCl(0.3mg/kgg, i.p.), $NAME(N^{G}-nitro-L-arginine$ methyl ester, 75mg/kg s.c.) and cisplatin(10mg/kg, i.p.). The gastric slow waves were measured for 30 minutes before and after administration of each solution(NS, JCH). Results : JCH 110.1mg/kg improved gastric emptying for 2 hrs(p=0.014). JCH 110.1mg/kg improved gastric emptying in the gastric wall injured rats(p=0.001). Under the delayed gastric emptying, JCH 110.1mg/kg improved gastric emptying in the group treated with atropine $sulfate(1.83{\pm}0.96$ vs $8.43{\pm}8.46$, p=0.003), but aggravated it with quinpirole $HCl(4.7{\pm}2.9$ vs $1.61{\pm}2.09$, p=0.021). Administration JCH 110.1mg/kg increased EGG power in rats. Conclusions : JCH stimulates gastric motility through the cholinergic pathway, so we expect that it would be effective in the treatment of dysmotility-like functional dyspepsia with low activity of vagus nerve.

• Toxicological Research
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• 제13권4호
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• pp.317-322
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• 1997

Acute delayed neurotoxicity of KH-502 [O.O-Diethyl O-(1-phenyyl-3-trifluoromethyl-5-pyrazoyl) thiophosphoric acid ester], an insecticide synthesized newly in Korea, was studied in White Leghorn hens. The doses were determined on the basis of preliminary $LD_{50}$ study. High, middle and low doses were determined to be 1123 mg/kg, 762 mg/kg and 518 mg/kg, respectively. The animals were pretreated with atropine (30 mg/kg) prior to administration of KH-502. The chemical was administrated at the first and 21st day of the study. As positive controls, animals were admlnistrated with triorthocresylphosphate (TOCP 1000 mg/kg and 500 mg/kg). Animals administrated with TOCP or KH-502 were sacrificed by perfusion-fixation at 21st and 42nd day of the study, respectively. The central and peripheral nerve tissues were routinely treated for microscopic observation. As results, eight, three, one, and one chickens died within 2 day after adminiatration with signs of cholinergic acute toxicity in high, middle low and TOCP dose-group (500 mg/kg), respectively. No abnormal clinical signs were observed in the survived chickens administrated with KH-502 in the duration of the study. The chickens in positive control groups showed ataxia and incoordination at the 14th day after administration of TOCP. From necropsy, macroscopic changes were not observed in all groups including positive control groups. Histopathologically, oxonal swelling with myelin loss, focal gliosis, distention around axonal space were observed in the spinal cords of the chickens administrated with TOCP 1000 mg/kg. The lesions were distinct in the dorsal and lateral funiculi of cervical spinal cord, in the lateral and ventral funiculi of thoracic spinal cord and in ventral funiculi of lumbosacral spinal cord. Axonal swelling and mlcrogliosis were infrequently observed in the chickens of other groups including negative control one. However, they were nonspecifically distributed in the spinal cords. In this study, we concluded that the new chemical, KH-502 did not have acute delayed neurotoxicity in White Leghorn hens.

• Toxicological Research
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• 제31권1호
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• pp.17-23
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• 2015

Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors, including memory deficits, decreased motor skills and psychotic behavior resembling Parkinson's disease. Hereditary hemochromatosis (HH) is a prevalent genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major cause of HH. Our previous study has demonstrated that olfactory Mn uptake is altered by HFE deficiency, suggesting that loss of HFE function could alter manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout ($Hfe^{-/-}$) and wild-type ($Hfe^{+/+}$) mice were intranasally-instilled with manganese chloride ($MnCl_2$ 5 mg/kg) or water daily for 3 weeks and examined for memory function. Olfactory Mn diminished both short-term recognition and spatial memory in $Hfe^{+/+}$ mice, as examined by novel object recognition task and Barnes maze test, respectively. Interestingly, $Hfe^{-/-}$ mice did not show impaired recognition memory caused by Mn exposure, suggesting a potential protective effect of Hfe deficiency against Mn-induced memory deficits. Since many of the neurotoxic effects of manganese are thought to result from increased oxidative stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in $Hfe^{+/+}$ mice, but not in $Hfe^{-/-}$ mice. In addition, Hfe deficiency up-regulated SOD1 and glutathione peroxidase activities. These results suggest a beneficial role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC. Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the PFC, indicating that blunted acetylcholine signaling could contribute to impaired memory associated with intranasal manganese. Together, our model suggests that disrupted cholinergic system in the brain is involved in airborne Mn-induced memory deficits and loss of HFE function could in part prevent memory loss via a potential up-regulation of anti-oxidant enzymes in the PFC.

• Biomolecules & Therapeutics
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• 제17권1호
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• pp.32-42
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• 2009

The purpose of the present study was to examine the effect of dihydrexidine, a full $D_1$ receptor agonist, on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland, and to establish its mechanism of action. Dihydrexidine (10-100 ${\mu}M$), perfused into an adrenal vein for 60 min, relatively produced dose- and time-dependent inhibition in the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Dihydrexidine itself did fail to affect basal CA output. Also, in adrenal glands loaded with dihydrexidine (30 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$), an activator of L-type $Ca^{2+}$ channels, cyclopiazonic acid (10 ${\mu}M$), an inhibitor of cytoplasmic $Ca^{2+}$-ATPase, and veratridine, an activator of voltage-dependent $Na+$ channels (10 ${\mu}M$), were also markedly inhibited, respectively. However, in the simultaneous presence of dihydrexidine (30 ${\mu}M$) and R (+)-SCH23390 (a selective antagonist of $D_1$ receptor, 3 ${\mu}M$), the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644, cyclopiazonic acid and veratridine were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory responses by dihydrexidinetreatment alone. In conclusion, these experimental results suggest that dihydrexidine significantly inhibits the CA secretion evoked by cholinergic stimulation (both nicotinic and muscarinic receptors) and membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of dihydrexidine may be mediated by inhibiting influx of both $Ca^{2+}$ and $Na^+$ into the cytoplasm as well as by suppression of $Ca^{2+}$ release from cytoplasmic calcium store through activation of dopaminergic $D_1$ receptors located on the rat adrenomedullary chromaffin cells.

• 대한수의학회지
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• 제14권1호
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• pp.33-40
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• 1974

It has been generally understood that the intestinal tracts are under the control of the autonomic nerves; the parasympathetics are excitatory and the sympathetics inhibitory. However, it is recently reported that the actions of these autonomic nerves in the newborn animals are shown to be different from those in the adult animals in some species. In order to elucidate the role of sympathetic innervation to the intestinal tracts, the effects of periarterial nerve stimulation were studied in the periarterial sympathetics-jejunum preparations of the chick and the effects of some autonomic drugs on the isolated muscle strips were also studied. The results obtained were as follows: 1. The periarterial stimulation in the periarterial sympathetics-jejunum preparation elicited the responses of three patterns; 1) contrcation followed by relaxation 2) contraction only 3) relaxation only. The excitatory response was most effective in the stimulus frequencies of 40 cps, whereas the inhibitory response was maximal in the stimulus frequencies of 30 cycle per second. 2. The excitatory response to the periarterial stimulation was not affected by the pretreatment with phenoxybenzamine, dibenamine, propranolol and atropine, whereas the inhibitory response was completely blocked by the pretreatment with phenoxybenzamine and propranolol. 3. In the periarterial syrnpathetics-jejunum preparation treated with reserpine, the periarterial stimulation evoked only contraction, and the contraction was not affected by the pretreatment with phenoxybenzamine, propranolol and atropine. 4. The administration of norepinephrine evoked a relaxation in the isolated jejunum muscle strips and the effect was completely blocked by the pretreatment with phenoxybenzamine. 5. The administration of isoproterenol produced a relaxation in the isolated jejunum muscle strips and the effect was not affected by pretreatment with phenoxybenzamine, whereas the effect was completely blocked by the pretratment with propranolol. 6) The administration of acetylcholine produced a marked contraction in the isolated jejunum muscle strips and the effect was completely abolished by the pretreatment of atropine. These experimental evidences indicate that the inhibitory response to the periarterial stimulation is due to adrenergic fibers and the excitatory response is due to neither adrenergic nor cholinergic component.

• 대한수의학회지
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• 제39권4호
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• pp.702-709
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• 1999

The present study was performed to elucidate the effects of extracellular $Ca^{2+}$ on contractile responses in isolated porcine coronary artery ring using by perivascular nerve stimulation (PNS). Especially, the study was focused on the source of $Ca^{2+}$ on $P_{2X}$-purinoceptor mediated muscle contraction which one of $P_2$-purinoceptor subtypes. The following results can be drawn from these studies : 1. The phasic contractions induced by PNS were inhibited with muscarinic receptor antagonist, atropine ($10^{-6}M$). 2. The phasic contractions induced by PNS were significantly inhibited by sequential treatment with atropine and adrenergic neural blocker, guanethidine ($10^{-6}M$). 3. The phasic contractions induced by PNS were inhibited with $P_{2X}$-purinoceptor desensitization by repetitive application of $\alpha$,$\beta$-Me ATP ($10^{-4}M$). 4. The phasic contractions induced by PNS were so weakened in calcium-free medium. 5. The phasic contractions induced by PNS were inhibited with calcium channel blocker, verapamil ($10^{-6}{\sim}5{\times}10^{-6}M$). 6. The phasic contractions induced by PNS on pretreated with verapamil ($10^{-6}{\sim}5{\times}10^{-6}M$) were not changed by $\alpha$,$\beta$-Me ATP ($10^{-4}M$). These results demonstrate that the neurogenic phasic contractions induced by PNS are due to adrenergic-, cholinergic- and $P_{2X}$-purinergic receptors and the origin of $Ca^{2+}$ on $P_{2X}$-purinoceptor mediated muscle contraction is extracellular $Ca^{2+}$ through plasmalemmal $Ca^{2+}$ channels.

• 대한수의학회지
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• 제47권4호
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• pp.371-378
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• 2007

To understand the role of $PM_{2X}/P_{2Y}$ receptor in cortex region of kidney and renal artery, molecular and functional analysis of $PM_{2X}/P_{2Y}$ receptor by pharmacophysiological skill in conventional swine tissues were performed. In functional analysis of $P_{2Y}$ receptor for vascular relaxation, 2-methylthio adenosine triphosphate, a strong agonist of $P_{2Y}$ receptor, induced relaxation of noradrenaline (NA)-precontracted renal artery in a dose-dependent manner. Strikingly, relaxative effect of ATP, 2-msATP, agonists of $P_{2Y}$ receptor, abolished by treatment of reactive blue 2, a putative $P_{2Y}$ receptor antagonist. In contrast, no significant differences of gene encoding $PM_{2X}/P_{2Y}$ and protein expression in immortalized suprachiasmatic nucleus from brain, primary isolated vascular smooth muscle cells from renal artery of pigs and HEK293 from human embryonic kidney under with/without adenosine triphosphate were observed. Taken together, the relationship between molecular and functional characteristic of $PM_{2X}/P_{2Y}$ receptors in conventional pig should be considered that they are another important factor which regulate the kidney function in swine. Based on this study, we propose the purinergic receptor as well as adrenergic and cholinergic receptors is an essential component of the renal homeostasis.

• 생약학회지
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• 제49권2호
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• pp.182-187
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• 2018

Many plant derived phytochemicals have been considered as the main therapeutic strategy against Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder, and the most predominant cause of dementia in the elderly. Cholinergic deficit, senile plaque/${\beta}$-amyloid ($A{\beta}$) peptide deposition and oxidative stress have been identified as three main pathogenic pathways which contribute to the progression of AD. We screened many different plant species for their effective use in both modern and traditional system of medicines. In this study, we tested that MeOH extract of the stem bark of Hopea chinensis (Merr.) Hand.-Mazz. (HCM) affects on the processing of Amyloid precursor portein (APP) from the APPswe over-expressing Neuro2a cell line. We showed that HCM reduced the secretion level of $A{\beta}42$ and $A{\beta}40$ in a dose dependent manner. We found that HCM increased over 1.5 folds of the secretion level of $sAPP{\alpha}$, a metabolite of ${\alpha}$-secretase. Furthermore, we found that HCM inhibited acetylcholinesterase activity in vitro. We suggest that the stem bark of Hopea chinensis may be a useful source to develop a therapeutics for AD.