• The Korean Journal of Pharmacology
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• v.20 no.2
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• pp.49-57
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• 1984

The exocrine pancreatic secretion is controlled mainly by gastrointestinal hormones as well as cholinergic nerves. The adrenergic influence on exocrine pancreas is thought not to he important and the evidences supporting this contention are still contradictory. In an effort to elucidate the adrenergic influence on the exocrine pancreas, we have determined the amylase release from pancreatic slices of rats treated with adrenergic drugs. The albino rats of either sex, weighing $60{\sim}80\;g$, were decapitated and the uncinate pancreata were isolated and incubated in screw top vials containing 2 ml krebs-Ringer bicarbonate buffer solution gassed with 95% $O_2$ and 5% $CO_2$. These vials were shaken continuously in a waterbath maintained at $37^{circ}C$, and enzyme release was stimulated with acetylcholine$(10^{-5}M)$. For chronic treatment methoxamine$(an\;{\alpha}-adrenergic\;agonist,\;5\;mg/kg)$, isoproterenol (a\;{\beta}-adrenergic\;agonist,\;10\;mg/kg) and reserpine (0.5 mg/kg) along with cholecystokinin octapeptide$(CCK-op,\;2{\mu}g/kg)$ were given i.p. in rats daily for 3, 5, 7, 9 or 12 days. For acute experiment these drugs were added directly to the incubation medium in a concentration of $10^{-5}M$ except CCK-OP $(10^{-9}M)$. The results are summarized as follows. 1) The addition of methoxamine, isoproterenol or reserpine to the incubation medium containing pancreatic slices augmented the release of amylase induced by acetylcholine and among them the effect of isoproterenol was most prominent. 2) Chronic treatment of methoxamine or reserpine caused enhancement of acetylcholine response in amylase release from pancreatic slice throughout the experimental period, but the amylase release was less than that of control by 12 days isoproterenol treatment. 3) In the pancreatic slices obtained from 12 days treatment of CCK-OP, the amylae release responding to acetylcholine was enhanced. By these finding it is suggested that methoxamine, isoproterenol and reserpine had marked influence on the exocrine pancreatic functions in rats and that these effects are due to their inherent actions rather than sympathetic nerve or adrenergic receptor function.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.71-78
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• 2001

Capsaicin, a pungent ingredient of hot pepper, elicits an intense burning pain when applied cutaneously and intradermally. Activation of capsaicin-gated channel in C-type dorsal root ganglion (DRG) neurons produces nonselective cationic currents. Although electrophysiological and biochemical properties of capsaicin-activated current $(I_{CAP})$ were studied, the regulatory mechanism and intracellular signaling pathway are still unclear. In the present study, we investigated the modulations of $I_{CAP}$ by DAMGO $({\mu}-opioid\;agonist)$ and cholecystokinin octapeptide (CCK-8). In 18 out of 86 cells, the amplitude of $I_{CAP}$ was significantly increased by DAMGO and completely reversed after washout, while $I_{CAP}$ was decreased by DAMGO in 25 cells. In 43 cells, DAMGO had no effect on $I_{CAP}$. Mean action potential duration was significantly different between 'increased-by-DAMGO' group and 'decreased-by-DAMGO' group. Mean amplitudes of $I_H$ were not significantly different between both groups. CCK-8 reversibly enhanced the amplitude of $I_{CAP}$ (5/13). DAMGO also increased $I_{CAP}$ amplitude significantly in the same cells. The amplitude of $I_{CAP}$ was increased in additive manner by combined applications of DAMGO and CCK-8 in these cells. These results suggest that DAMGO and CCK-8 can either increase or decrease $I_{CAP}$ presumably depending on the subtypes of DRG cells and classified by electrophysiological properties.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.1
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• pp.7-15
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• 2004

Nitric oxide (NO) system has been implicated in a wide range of physiological functions in the nervous system. However, the role of NO in regulating the neural activity in the gustatory zone of nucleus tractus solitarius (NTS) has not been established. The present study was aimed to investigate the role of NO in the gustatory NTS neurons. Sprague-Dawley rats, weighing about 50 g, were used. Whole cell patch recording and immunohistochemistry were done to determine the electrophysiological characteristics of the rostral gustatory nucleus of the tractus solitaries and distribution of NO synthases (NOS). Neuronal NOS (nNOS) immunoreactivity was strongly detected along the solitary tract extending from rostral to caudal medulla. Resting membrane potentials of NTS neurons were $-49.2{\pm}2\;mV$ and action potential amplitudes were $68.5{\pm}2\;mV$ with a mean duration measured at half amplitude of $1.7{\pm}0.3\;ms$. Input resistance, determined from the response to a 150 ms, -100 pA hyperpolarizing current pulse, was $385{\pm}15\;M{\Omega}$, Superfusion of SNAP or SNP, NO donors, produced either hyperpolarization (68%), depolarization (5%), or no effect (27%). The hyperpolarization was mostly accompanied by a decrease in input resistance. The hyperpolarization caused by SNAP or SNP increased the time to initiate the first action potential, and decreased the number of action potentials elicited by current injection. SNP or SNAP also markedly decreased the number of firing neural discharges of the spontaneous NTS neural activity under zero current. Superfusion of L-NAME, a NOS inhibitor, slightly depolarized the membrane potential and increased the firing rate of NTS neurons induced by current injection. ODQ, a soluble guanylate cyclase inhibitor, ameliorated the SNAP-induced changes in membrane potential, input resistance and firing rates. 8-Br-cGMP, a non-degradable cell-permeable cGMP, hyperpolarized the membrane potential and decreased the number of action potentials. It is suggested that NO in the gustatory NTS has an inhibitory role on the neural activity of NTS through activating soluble guanylate cyclase.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.309-318
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• 2015

Alcohol consumption increases the risk of type 2 diabetes. However, its effects on prediabetes or early diabetes have not been studied. We investigated endoplasmic reticulum (ER) stress in the pancreas and liver resulting from chronic alcohol consumption in the prediabetes and early stages of diabetes. We separated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 diabetic animal model, into two groups based on diabetic stage: prediabetes and early diabetes were defined as occurrence between the ages of 11 to 16 weeks and 17 to 22 weeks, respectively. The experimental group received an ethanol-containing liquid diet for 6 weeks. An intraperitoneal glucose tolerance test was conducted after 16 and 22 weeks for the prediabetic and early diabetes groups, respectively. There were no significant differences in body weight between the control and ethanol groups. Fasting and 120-min glucose levels were lower and higher, respectively, in the ethanol group than in the control group. In prediabetes rats, alcohol induced significant expression of ER stress markers in the pancreas; however, alcohol did not affect the liver. In early diabetes rats, alcohol significantly increased most ER stress-marker levels in both the pancreas and liver. These results indicate that chronic alcohol consumption increased the risk of diabetes in prediabetic and early diabetic OLETF rats; the pancreas was more susceptible to damage than was the liver in the early diabetic stages, and the adaptive and proapoptotic pathway of ER stress may play key roles in the development and progression of diabetes affected by chronic alcohol ingestion.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.393-398
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• 2012

Mast cells are involved in allergic responses, protection against pathogens and autoimmune diseases. Dexamethasone (Dex) and other glucocorticoids suppress $Fc{\varepsilon}RI$-mediated release of inflammatory mediators from mast cells. The inhibition mechanisms were mainly investigated on the downstream signaling of Fc receptor activations. Here, we addressed the effects of Dex on Fc receptor expressions in rat mast cell line RBL-2H3. We measured mRNA levels of Fc receptors by real-time PCR. As expected, Dex decreased the mRNA levels of activating Fc receptor for IgE ($Fc{\varepsilon}R$) I and increased the mRNA levels of the inhibitory Fc receptor for IgG $Fc{\gamma}RIIb$. Interestingly, Dex stimulated transcriptions of other activating receptors such as Fc receptors for IgG ($Fc{\gamma}R$) I and $Fc{\gamma}RIII$. To investigate the mechanisms underlying transcriptional regulation, we employed a transcription inhibitor actinomycin D and a translation inhibitor cycloheximide. The inhibition of protein synthesis without Dex treatment enhanced $Fc{\gamma}RI$ and $Fc{\gamma}RIII$ mRNA levels potently, while $Fc{\varepsilon}RI$ and $Fc{\gamma}RIIb$ were minimally affected. Next, we examined expressions of the Fc receptors on cell surfaces by the flow cytometric method. Only $Fc{\gamma}RIIb$ protein expression was significantly enhanced by Dex treatment, while $Fc{\gamma}RI$, $Fc{\gamma}RIII$ and $Fc{\varepsilon}RI$ expression levels were marginally changed. Our data showed, for the first time, that Dex regulates Fc receptor expressions resulting in augmentation of the inhibitory receptor $Fc{\gamma}RIIb$.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.1
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• pp.1-7
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• 2007

Altered environmental gravity, including both hypo- and hypergravity, may result in space adaptation syndrome. To explore the characteristics of this adaptive plasticity, the expression of immediate early gene c-fos mRNA in the vestibular related tissues following an exposure to hypergravity stimulus was determined in rats. The animals were subjected to a force of 2 g (twice earth's gravity) for 1, 3, or 12 h, and were examined poststimulus at 0, 2, 6, 12, and 24 h. RT-PCR (reverse transcription polymerase chain reaction) and real-time quantitative RT-PCR were adopted to analyze temporal changes in the expression of c-fos mRNA. The hypergravity stimulus increased the expression of c-fos mRNA in the vestibular ganglion, medial vestibular nucleus, inferior vestibular nucleus, hippocampus, cerebellum, and cortex. The peak expression occurred at 0 h poststimulation in animals stimulated with hypergravity for 1 h, and at 6 h poststimulus in those stimulated for 3 h. In contrast, those stimulated for 12 h exhibited dual peaks at 0 and 12 h poststimulus. Bilateral labyrinthectomy markedly attenuated the degree of c-fos mRNA expression. Glutamate receptor antagonist also dramatically attenuated the degree of c-fos mRNA expression. These results indicate that expression of c-fos mRNA in response to hypergravity occurs in the vestibular related tissues of the central nervous system, in which peripheral vestibular receptors and glutamate receptors play an important role. The temporal pattern of c-fos mRNA expression depended on the duration of the hypergravity stimulus.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.5
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• pp.245-251
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• 2008

Single-channel recordings of TASK-1 and TASK-3, members of two-pore domain $K^+$ channel family, have not yet been reported in dorsal root ganglion (DRG) neurons, even though their mRNA and activity in whole-cell currents have been detected in these neurons. Here, we report single-channel kinetics of the TASK-3-like $K^+$ channel in DRG neurons and up-regulation of TASK-3 mRNA expression in tissues isolated from animals with spinal cord injury (SCI). In DRG neurons, the single-channel conductance of TASK-3-like $K^+$ channel was $33.0{\pm}0.1$ pS at - 60 mV, and TASK-3 activity fell by $65{\pm}5%$ when the extracellular pH was changed from 7.3 to 6.3, indicating that the DRG $K^+$ channel is similar to cloned TASK-3 channel. TASK-3 mRNA and protein levels in brain, spinal cord, and DRG were significantly higher in injured animals than in sham-operated ones. These results indicate that TASK-3 channels are expressed and functional in DRG neurons and the expression level is up-regulated following SCI, and suggest that TASK-3 channel could act as a potential background $K^+$ channel under SCI-induced acidic condition.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.311-319
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• 2018

Mitochondrial calcium overload is a crucial event in determining the fate of neuronal cell survival and death, implicated in pathogenesis of neurodegenerative diseases. One of the driving forces of calcium influx into mitochondria is mitochondria membrane potential (${\Delta}{\psi}_m$). Therefore, pharmacological manipulation of ${\Delta}{\psi}_m$ can be a promising strategy to prevent neuronal cell death against brain insults. Based on these issues, we investigated here whether nobiletin, a Citrus polymethoxylated flavone, prevents neurotoxic neuronal calcium overload and cell death via regulating basal ${\Delta}{\psi}_m$ against neuronal insult in primary cortical neurons and pure brain mitochondria isolated from rat cortices. Results demonstrated that nobiletin treatment significantly increased cell viability against glutamate toxicity ($100{\mu}M$, 20 min) in primary cortical neurons. Real-time imaging-based fluorometry data reveal that nobiletin evokes partial mitochondrial depolarization in these neurons. Nobiletin markedly attenuated mitochondrial calcium overload and reactive oxygen species (ROS) generation in glutamate ($100{\mu}M$)-stimulated cortical neurons and isolated pure mitochondria exposed to high concentration of $Ca^{2+}$ ($5{\mu}M$). Nobiletin-induced partial mitochondrial depolarization in intact neurons was confirmed in isolated brain mitochondria using a fluorescence microplate reader. Nobiletin effects on basal ${\Delta}{\psi}_m$ were completely abolished in $K^+-free$ medium on pure isolated mitochondria. Taken together, results demonstrate that $K^+$ influx into mitochondria is critically involved in partial mitochondrial depolarization-related neuroprotective effect of nobiletin. Nobiletin-induced mitochondrial $K^+$ influx is probably mediated, at least in part, by activation of mitochondrial $K^+$ channels. However, further detailed studies should be conducted to determine exact molecular targets of nobiletin in mitochondria.

• Restorative Dentistry and Endodontics
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• v.24 no.2
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• pp.372-380
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• 1999

The purpose of this study was to investigate the distribution of calcitonin gene-related peptide(CGRP) containing nerve fivers after pulp exposure in rats. The Spague-Dawley rats weighing about 250 - 300g were used. The animals were devided into normal control group and experimental groups. Experimental animals were sacrified on 2, 4, 7, 10 days after pulp exposure. The maxillary teeth and alveolar bone were removed and immersed in the 4% paraformaldehyde plus 0.1M phosphate buffer (pH 7.4). Serial frozen $50{\mu}m$ thick sections were cut with a cryostat. In the immunohistochemical staining procedure, the rabbit CGRP antibody was used as a primary antibody. The sections were incubated for 48 hours at $4^{\circ}C$, and placed into biotinylated anti-rabbit IgG as a secondary antibody and incubated in ABC (avidin-biotin complex), The sections were visualized by 0.05% 3.3 diaminobenzidine tetrahydrochloride. The results of this study were as follows: 1. In control group, CGRP containing nerve fibers ran parallel to the long axis of root and reached the coronal pulp. They were distributed on Raschkow plexus under the odontoblastic layer. 2. In 2 day group after pulp exposure, tissue necrosis and acute inflammation occurred and CGRP containing nerve fibers increased. In 4 day group, the necrotic tissue extended to the pulp and CGRP containing nerve fibers were distributed around the inflammation zone. 3. In 7 day group after pulp exposure, pulp necrosis occurred, and in 10 day group, the abscess under the necrotic pulp extended to the root apex area and CGRP containing nerve fibers were not observed in root canals. 4.The sprouting of CGRP nerve fibers was most remarkable at the pulp chamber under injury in 4 day group, and it was found at inflammation zone under the necrotic tissue in 7 day group and the remaining root pulp tissue in 10 day group. As mentioned above, CGRP nerve fibers had a tendency to increase around the inflammatory zone, especially around the acute inflammation tissue, when compared with control group. It is suggested that CGRP nerve fibers maybe related to the control of inflammatory response of pulp tissue.

• Applied Biological Chemistry
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• v.22 no.3
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• pp.173-180
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• 1979

SDS gel electrophoresis has been employed to examine the changes in distribution of three major classes of nuclear proteins extracted from isolated liver nuclei in response to refeeding of starved rats with a fat-free high carbohydrate diet and following insulin injection into streptozotocin-diabetic rats. The relative quantity of electrophoretically separated proteins in the fraction showed marked changes with 0.14 NaCl extracts, but not with histones and phenol soluble non-histone proteins. During 48h starvation at least five proteins ranging in molecular weight from 50,000 to 180,000 daltons decreased relative to normal controls while a protein with 36,000 daltons was increased. Refeeding the starved rats with a high carbohydrate diet reversed these changes over 24 h. Insulin injection into streptozotocin-diabetic rats increased levels of the set of five 0.14 M NaCl soluble proteins identified from refeeding experiment of starved rats. The 36,000 daltons protein was also diminished. These results indicate that changes in distribution of certain nuclear proteins in 0.14M NaCl extracts are associated with the control of nuclear activity ralated to known insulin-signalled modulation and induction of cytosolic lipogenic enzymes.