• The Korean Journal of Pain
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• v.9 no.1
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• pp.39-45
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• 1996

Tachyphylaxis to local anesthetics has shown to be promote longer interanalgesic intervals between injections. Previous study demonstrated thermal hyperalgesia accelerates development of tachyphylaxis to sciatic nerve blockade in rats, while MK-801 prevents development of tachyphylaxis. Dextromethorphan is one of NMDA receptor antagonist similar to MK-801. A hypothesis that dextromethorphan would prevent the development of tachyphylaxis was tested in this study. A catheter was surgically implanted along the sciatic nerve a in rat. After recovery from surgery, the animal received repeated injections of 3% 2-chloroprocaine followed by motor block testing with or without hot-plate testing at $56^{\circ}C$. In other experiments, dextromethorphan was administrered by intraperiotneal injection prior to an injection of local anesthetic therough the implanted catheter. Sensory and motor testing was then carried out. Rats injected with 2-chloroprocaine and subjected to hot-plate testing, developed tachyphylaxis to motor and sensory blockade. However, animals pretreated with dextromethorphan did not develop tachyphylaxis over series of three injections. Dextromethorphan seems to prevent development of tachyphylaxis to sciatic nerve blockade in this rat model. Dextromethorphan, one of N-Methyl-D-aspartate receptor antagonist, can be applied to prolong the effect of local anesthetic.

• The Korean Journal of Physiology
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• v.17 no.2
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• pp.109-117
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• 1983

The effects of histamine on contraction of rabbit taenia coli were studied. The results obtained were as follows: 1) The contractile response to histamine was appeared at the concentration of $10^{-7}M$ and increased in a dose-dependent manner to the concentration of $10^{-4}M$. 2) The magnitude of the histamine-induced contractile response was declined during short-term exposure in rabbit taenia coli. After 40-min exposure to histamine, the contractile response did not altered. 3) Histamine-induced contraction was not influenced by hexamethonium$(10^{-4}M)$, propranolol$(10^{-4}M)$ and phenoxybenzamine$(10^{-6}M)$. 4) $H_1-receptor$ blockade such as chlorpheniramine$(10^{-6}M)$ and pyrilamine$(10^{-6}M)$ completely abolished the response of the taenia coli to exogenous histamine, while $H_2-receptor$ blockade (cimetidine, $10^{-6}M$) did not alter. 5) After the treatment of verapamil the histamine-induced contraction was significantly inhibited, but in the treatment of 2 mM $La^{3+}$ it was not influenced. 6) In the absence of $Ca^{2+}$, histamine induced contraction in the different manner of acetylcholine. When taenia coli war treated with atropine$(10^{-6}M)$ which was completely blocked the contraction by acetylcholine$(10^{-4}M)$, histamine-induced contraction was not altered. These results suggest that in the rabbit taenia coli exogenous histamine induced contraction through $H_1$-receptor, but not through the mechanism of acetylcholine.

• Journal of Yeungnam Medical Science
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• v.34 no.1
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• pp.43-54
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• 2017

Background: Extracellular sulfatases (Sulfs), sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), play a pivotal role in cell signaling by remodeling the 6-O-sulfation of heparan sulfate proteoglycans on the cell surface. The present study examined the effects of Sulfs on angiotensin II (Ang II)-induced hypertensive mediator expression and vascular smooth muscle cells (VSMCs) proliferation in spontaneously hypertensive rats (SHR). Methods: Ang II receptors, 12-lipoxygenase (12-LO), and endothelin-1 (ET-1) messenger RNA (mRNA) expressions in SHR VSMCs were analyzed by real-time polymerase chain reaction and Western blotting. VSMCs proliferation was determined by [$^3H$]-thymidine incorporation. Results: Basal Sulfs mRNAs expression and enzyme activity were elevated in SHR VSMCs. However, Sulfs had no effect on the basal or Ang II-induced 12-LO and ET-1 mRNA expression in SHR VSMCs. The inhibition of Ang II-induced 12-LO and ET-1 expression by blockade of the Ang II type 2 receptor ($AT_2\;R$) pathway was not observed in Sulf1 siRNA-transfected SHR VSMCs. However, Sulf2 did not affect the action of $AT_2\;R$ inhibitor on Ang II-induced 12-LO and ET-1 expression in SHR VSMCs. The down-regulation of Sulf1 induced a reduction of $AT_2\;R$ mRNA expression in SHR VSMCs. In addition, the inhibition of Ang II-induced VSMCs proliferation by blockade of the $AT_2\;R$ pathway was mediated by Sulf1 in SHR VSMCs. Conclusion: These findings suggest that extracellular sulfatase Sulf1 plays a modulatory role in the $AT_2\;R$ pathway that leads to an Ang II-induced hypertensive effects in SHR VSMCs.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.4
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• pp.327-335
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• 2009

The aim of this study was to determine whether losartan, an angiotensin II (Ang II) type 1 ($AT_1$) receptor could influence the CA release from the isolated perfused model of the rat adrenal medulla. Losartan (5${\sim}$50 ${\mu}$M) perfused into an adrenal vein for 90 min produced dose- and time-dependent inhibition of the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM, a direct membrane depolarizer), DMPP (100 ${\mu}$M) and McN-A-343 (100 ${\mu}$M). Losartan failed to affect basal CA output. Furthermore, in adrenal glands loaded with losartan (15 ${\mu}$M) for 90 min, 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), veratridine (100 ${\mu}$M, an activator of $Na^+$ channels), and Ang II (100 nM) were markedly inhibited. However, at high concentrations (150${\sim}$300 ${\mu}$M), losartan rather enhanced the CA secretion evoked by ACh. Collectively, these experimental results suggest that losartan at low concentrations inhibits the CA secretion evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization from the rat adrenal medulla, but at high concentration it rather inhibits ACh-evoked CA secretion. It seems that losartan has a dual action, acting as both agonist and antagonist to nicotinic receptors of the rat adrenal medulla, which might be dependent on the concentration. It is also thought that this inhibitory effect of losartan may be mediated by blocking the influx of both $Na^+$ and $Ca^{2+}$ into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is thought to be relevant to the $AT_1$ receptor blockade, in addition to its enhancement of the CA release.

• The Korean Journal of Physiology
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• v.29 no.1
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• pp.91-102
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• 1995

The role of neurohumoral mechanisms in the regulation of cardiovascular functions and the effects of ethanol (EOH) on these mechanisms were examined in hemorrhaged conscious Wistar rats. The rats were bled at a constant rate (2 ml/kg/min) through the femoral artery until mean arterial pressure (MAP) was reduced by 30 mmHg. We studied the responses to hemorrhage 1) under normal conditions (Normal), and after pretreatments with 2) neural blockade (NB), pentolinium, 3) arginine vasopressin V1-receptor antagonist (AVPX) + NB, 4) angiotensin II ATI-receptor antagonist (AngIIX) + NB, 5) combined humoral blockade (HB), and 6) neurohumoral blockade. Intravenous administration of 30% EOH (6.3 ml/kg) attenuated the baroreceptor reflex sensitivity, and enhanced the depressor action of AngIIX. During hemorrhage, NB produced a faster fall ill MAP than Normal both in the saline and EOH groups. However, HB accelerated the rate of fall in MAP only in the EOH group. The recovery from hemorrhagic hypotension was not different between NB and Normal rats, but was attenuated in HB rats in the saline group. Under NB, AngIIX, but not AVPX, retarded the recovery rate compared with NB alone. EOH attenuated the recovery of MAP after hemorrhage in Normal rats, but completely abolished the recovery in HB rats. We conclude that 1) the maintenance of MAP during hemorrhage is mediated almost entirely by the autonomic functions, 2) angiotensin II plays an important role in the recovery from hemorrhagic hypotension, but AVP assumes little importance, 3) AVP release largely depends on the changes in blood volume, whereas renin release depends on the changes in blood pressure rather than blood volume, and 4) EOH increases the dependence of cardiovascular regulation on angiotensin II and impairs the recovery from hemorrhagic hypotension through the attenuation of autonomic functions.

• Journal of Korean Neurosurgical Society
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• v.39 no.2
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• pp.130-135
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• 2006

Objective : After ischemic stroke, partial recovery of function frequently occurs and may depend on the plasticity of axonal connections. Here, we examine whether blockade of the Nogo/NogoReceptor[NgR] pathway might enhance axonal sprouting and thereby recovery after focal brain infarction. Methods : Adult male Sprague Dawley rats weighing $250{\sim}350g$ were used. Left middle cerebral artery occlusion[MCAO] was induced with a intraluminal filament. An osmotic mini pump [Alzet 2ML4, Alza Scientific Products, Palo Alto, CA] for the infusion of NgR-Ecto[310]-Fc to block Nogo/NgR pathway was implanted 1 week after cerebral ischemia. Prior to induction of ischemia, all animals received training in the staircase and rotarod test. Two weeks after biotin dextran amine injection, animals were perfused transcardially with PBS, followed by 4% paraformadehyde/PBS solution. Brain and cervical spinal cord were dissected. Eight coronal sections spaced at 1mm intervals throughout the forebrain of each animal with cresyl violet acetate for determination of infarction size. Images of each section were digitized and the infarct area per section was measured with image analysis software. Results : Histological examination at 11 weeks post-MCAO demonstrates reproducible stroke lesions and no significant difference in the size of the stroke between the NgR[310]Ecto-Fc protein treated group and the control group. Behavioral recovery is significantly better and more rapid in the NgR-Ecto[310]-Fe treated group. Blockade of NgR enhances axonal sprouting from the uninjured cerebral cortex and improves the return of motor task performance. Conclusion : Pharmacological interruption of NgR allows a greater degree of axonal plasticity in response this is associated with improved functional recovery of complicated motor tasks.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.1
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• pp.99-109
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• 2013

The aim of this study was to determine whether fimasartan, a newly developed $AT_1$ receptor blocker, can affect the CA release in the isolated perfused model of the adrenal medulla of spontaneously hypertensive rats (SHRs). Fimasartan (5~50 ${\mu}M$) perfused into an adrenal vein for 90 min produced dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM, a direct membrane depolarizer), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Fimasartan failed to affect basal CA output. Furthermore, in adrenal glands loaded with fimasartan (15 ${\mu}M$), 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 (100 ${\mu}M$, an activator of $Na^+$ channels) as well as by angiotensin II (Ang II, 100 nM), were markedly inhibited. In simultaneous presence of fimasartan (15 ${\mu}M$) and L-NAME (30 ${\mu}M$, an inhibitor of NO synthase), the CA secretory responses evoked by ACh, high $K^+$, DMPP, Ang II, Bay-K-8644, and veratridine was not affected in comparison of data obtained from treatment with fimasartan (15 ${\mu}M$) alone. Also there was no difference in NO release between before and after treatment with fimasartan (15 ${\mu}M$). Collectively, these experimental results suggest that fimasartan inhibits the CA secretion evoked by Ang II, and cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of fimasartan may be mediated by blocking the influx of both $Na^+$ and $Ca^{2+}$ through their ion channels into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is relevant to $AT_1$ receptor blockade without NO release.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.3
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• pp.149-155
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• 2003

The aim of the present study was to examine the effects of platycodin D and $D_3$, which are active components derived from the roots of Platycodon grandiflorum A. DC., on the contractile force of the i3olated rat aorta and blood pressure of the anesthetized rat, and also to elucidate its mechanism of action. Both phenylephrine (an adrenergic ${\alpha}1$-receptor agonist) and high potassium (a membranedepolarizing agent) caused great contractile responses in the isolated aortic strips. Platycodin D at high concentration $(24{\mu}g/ml)$ inhibited contractile responses induced by phenylephrine $(10^{-5}\;M)$ and high potassium $(5.6{\times}10^{-2}\;M)$, while low concentrations of platycodin D $(4{\sim}8{\mu}g/ml$) did not affect those responses. However, platycodin $D_3\;(8{\sim}32{\mu}g/ml)$ did not alter the contractile responses evoked by phenylephrine and high $K^+$. Interestingly, the infusion of platycodin $D_3$ (1.0 mg/kg/30 min) significantly reduced the pressor responses induced by intravenous norepinephrine. However, platycodin $D_3$ (1.0 mg/kg/30 min) did not affect them. Taken together, these results show that intravenously administered platycodin D depresses norepinephrine-induced pressor responses in the anesthetized rat, at least partly through the blockade of adrenergic ${\alpha}1$-receptors. Platycodin D also caused vascular relaxation in the isolated aortic strips of the rat via the blockade of adrenergic ${\alpha}1$-receptors, in addition to an unknown direct mechanism. However, platycodin $D_3$ did not affect both norepinephrine-induced pressor responses and the isolated rat aortic contractile responses evoked by phenylephrine and high potassium. Based on these results, there seems to be much difference in the mode of action between platycodin D and platycodin $D_3$.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.138-141
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• 1998

Neuroleptic malignant syndrome (NMS) is an uncommon but potentially fatal idiosyncratic reaction to neuroleptics, characterized by muscular rigidity, fever, autonomic dysfunction, and altered consciousness. The major theories to explain NMS is central dopaminergic blockade, but it is unclear. Risperidone is a new antipsychotic drug, a benzisoxazole derivative that blocks dopamine $D_2$ receptor and serotonin type 2 receptor. The comparatively greater serotonin-blocking activity is believed to give risperidone the specific property of not causing any more extrapyramidal side effects than conventional antipsychotics at the optimal dose of 4-8mg/day. It is postulated that risperidone is unlikely to cause NMS. Here, we report a case of risperidone induced neuroleptic malignant syndrome.

• Korean Journal of Anesthesiology
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• v.71 no.6
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• pp.476-482
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• 2018

Background: Several types of receptors are found at neuromuscular presynaptic membranes. Presynaptic inhibitory $A_1$ and facilitatory $A_{2A}$ receptors mediate different modulatory functions on acetylcholine release. This study investigated whether adenosine $A_1$ receptor agonist contributes to the first twitch tension (T1) of train-of-four (TOF) stimulation depression and TOF fade during rocuronium-induced neuromuscular blockade, and sugammadex-induced recovery. Methods: Phrenic nerve-diaphragm tissues were obtained from 30 adult Sprague-Dawley rats. Each tissue specimen was randomly allocated to either control group or 2-chloroadenosine (CADO, $10{\mu}M$) group. One hour of reaction time was allowed before initiating main experimental data collection. Loading and boost doses of rocuronium were sequentially administered until > 95% depression of the T1 was achieved. After confirming that there was no T1 twitch tension response, 15 min of resting time was allowed, after which sugammadex was administered. Recovery profiles (T1, TOF ratio [TOFR], and recovery index) were collected for 1 h and compared between groups. Results: There were statistically significant differences on amount of rocuronium (actually used during experiment), TOFR changes during concentration-response of rocuronium (P = 0.04), and recovery profiles (P < 0.01) of CADO group comparing with the control group. However, at the initial phase of this experiment, dose-response of rocuronium in each group demonstrated no statistically significant differences (P = 0.12). Conclusions: The adenosine $A_1$ receptor agonist (CADO) influenced the TOFR and the recovery profile. After activating adenosine receptor, sugammadex-induced recovery from rocuronium-induced neuromuscular block was delayed.