• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.43-43
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• 2003

Large-conductance $Ca^{2+}$-actived $K^{+}$ channels ($BK_{Ca}$ channels) play a key role in setting the pace of contractile activity in muscle and are involved in the regulation of neurotransmitter release in neuron. $BK_{Ca}$ channels are activated by depolarizing membrane potential and the elevated level of intracellular calcium. Using yeast-two hybrid assay, we have identified a novel protein interacting with the cytosolic carboxyl terminus of rSlo, the brain isoform of rat large-conductance $Ca^{2+}$-activated $K^{+}$ channel $\alpha$-subunit. The novel gene encodes 51 kDa protein and is named as SIRK(rSlo-interacting RGS-like protein). SIRK is expressed in various tissues and localized in the cytosolic and the membrane fraction. Biochemical and immunological studies indicated that SIRK physically interacted with the cytosolic region of rSlo. To investigate whether SIRK can modulate the activity of rSlo, GFP-fused SIRK and rSlo were transiently transfected into COS-7 cells and the effects of SIRK was studied using electrophysiological means. We concluded that the overexpression of SIRK alters the surface expression of rSlo channel with only a limited effect on the biophysical characteristics of the channel.the channel.

• The Journal of the Korea Contents Association
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• v.9 no.4
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• pp.340-346
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• 2009

Lithium has only a minimal effect on basal glucose transport activity, instead that lithium markedly increased the sensitivity of glucose transport to insulin by increasing in insulin induced glucose transport activity. And Lithium increases in insulin responsiveness as well. Previous studies has reported this enhancement of lithium to stimulate the glucose transport process is not only limited to insulin, it also induce the increases in the sensitivity of glucose transport by submaximal contractile activity. The preliminary study, however, leads that Lithium possibly improves the responsiveness of glucose transport with maximal muscle contraction. In this study, we investigated the effect of Lithium on contraction for the maximal glucose transport. For the purpose of this study, Epitrochlearis muscles of SD rat were isolated and treated Lithium with electric contraction and/or insulin to activate the maximal glucose transport. The results support that Lithium improves the responsiveness of glucose transport through potentiates contraction and/or insulin induced-glucose uptake in muscle. Consequently Lithium treated with muscle contraction and insulin has the important potential to improve the insulin resistance and diabetes.

• Journal of Korean Physical Therapy Science
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• v.13 no.2
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• pp.137-145
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• 2006

We investigated whether increased contractile responsiveness to epidermal growth factor (EGF) is associated with altered activation of mitogen-activated protein kinase (MAPK) in the aortic smooth muscle of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. EGF induced contraction and MAPK activity in aortic smooth muscle strips, which were significantly increased in tissues from the DOCA-salt hypertensive rats compared with those from sham-operated rats. AG1478, PD98059, and LY294002, inhibitors of EGF receptor (EGFR) tyrosine kinase, MAPK/extracellular signal-regulated kinase (ERK) kinase, and phosphatidylinositol 3-kinase (PI3K), respectively, inhibited the contraction and the activity of ERK1/2 that were elevated by EGF. Y27632 and GF109203X, inhibitors of Rho kinase and protein kinase C, respectively, attenuated EGF-induced contraction, with no diminution of ERK1/2 activity. Although EGF also elevated the activity of EGFR tyrosine kinase in both sham-operated and DOCA-salt hypertensive rats, the expression and the magnitude of activation did not differ between strips. These results strongly suggest that EGF induces contraction by the activation of ERK1/2, which is regulated by the PI3K pathway in the aortic smooth muscle of DOCA-salt hypertensive rats.

• Journal of Microbiology and Biotechnology
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• v.30 no.5
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• pp.649-661
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• 2020

This study examined the laxative effects of hot-water extracts of Hovenia dulcis Thunb. (HD), Phyllostachys pubescens Mazel (PM), and a 2:8 mixture of both (HP) in two chronic constipation models. For the loperamide-induced constipation model, animals were divided into an untreated group, negative control group (loperamide 4 mg/kg), positive control group (bisacodyl 4 mg/kg) group, and six treatment groups (HP 100 or 400, HD 50 or 100, and PM 100 or 400 mg/kg). For the low-fiber diet-induced constipation model, animals were divided into an untreated group (normal diet), negative control group (low-fiber diet), positive control group (Agio granule, 620 mg/kg), and the same treatment groups. Fecal number, weight, fecal water content, and intestinal transit ratio were higher in the groups treated with HP, HD, and PM than in the groups treated with loperamide or low-fiber diet. Thickness of colon mucosa and muscle layers were increased in the treated groups. Colon tension increased in the HP groups, and [Ca²⁺]i measurements using fura-2 as an indicator showed that HP inhibits ATP-mediated Ca²⁺ influx in IEC-18 cells. These results showed that the HP mixture has laxative activity by increased mucin secretion and inducing contractile activity and relaxation. It may be a useful therapeutic strategy for ameliorating in chronic constipation.

• Proceedings of the Korean Biophysical Society Conference
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• 1999.06a
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• pp.61-62
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• 1999

;The mechanisms inducing hypertension are actively investigated and are still challenging topics. Basically hypertension must be caused by the disorder of $Ca^{2+}$ metabolism in vascular smooth muscle, such as the increase of $Ca^{2+}$ influx, the decrease of ci+ efflux, or the change of sensitivity of contractile protein etc. The one of cause of the increase of ci+ influx may be the change of ci+ channel activity. Even though the relationships of ci+ channel activity and hypertension were studied using various hypertension models, still it is not clear how much change of $Ca^{2+}$ channel activity in diabetes mellitus (DM) induced hypertension is occurred. We induced DM hypertension in SD rat and compared the $Ca^{2+}$ channel activity with age-matched normotensive SD rat. For inducing DM hypertension, left kidney was removed with 200 gm rat and, after 1 month, 60 mg/kg of streptozotocin was injected into peritoneal space to induce diabetes mellitus. Usually after 4-6 weeks, hypertension was fully induced. For isolating vascular smooth muscle cells (VSMC), we used mesenteric arteriole (3rd - 4th branch of mesenteric artery) of which diameter is below 150 urn. VSMCs were isolated enzymatically. $Ca^{2+}$ current was measured using whole cell patch clamp technique. All experiments were performed at $37^{\circ}C$. The cell membrane area of VSMC of DM hypertensive rat is larger than that of control VSMC($36.6{\pm}3.64{\;}pF{\;}vs{\;}22.4{\pm}1.29{\;}pF, {\;}mean{\pm}S.E.$) When we compared the current amplitude, the $Ca^{2+}$ current amplitude in VSMC of DM hypertensive rat is much larger than that in VSMC of normotensive age-matched rat. After $Ca^{2+}$ current amplitude was normalized by cell membrane area, the current amplitude in DM hypertension is increased to $249.1{\pm}15.9{\;}%{\;}(mean{\pm}S.E.M)$, which means the ;absolute current amplitude is about 4 times larger in DM hypertension. When we compared the steady state activation and inactivation. there were no noticeable differences. From these results. one of cause of the DM hypertension is due to the increase of $Ca^{2+}$ current amplitude. But it need further study why the $Ca^{2+}$ current is so large in VSMC of DM hypertension and how much $Ca^{2+}$ influx through $Ca^{2+}$ channel contribute to the increase of intracellular $Ca^{2+}$ and eventually contribute to development of hypertension.ypertension.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.576-587
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• 2009

Background: The up-regulation of the nitric oxide (NO)-cGMP pathway might be involved in the change of vascular reactivity in rats 3 days after they suffer acute myocardial infarction. However, the underlying mechanism for this has not been clarified. Material and Method: Acute myocardial infarction (AMI) was induced by occluding the left anterior descending coronary artery (LAD) for 30 min (Group AMI), whereas the sham-operated control rats were treated similarly without LAD occlusion (Group SHAM), The concentration-response relationships for phenylephrine (PE), KCl, acetylcholine (Ach) and sodium nitroprusside (SNP) were determined in the endothelium intact E(+) and endothelium denuded E(-) thoracic aortic rings from the rats 3 days after AMI or a SHAM operation. The concentration-response relationships of PE in the E(+) rings from the AMI rats were compared with those relationships in the rings pretreated with nitric oxide synthase (NOS) inhibitor $N{\omega}$-nitro-L-arginine methyl ester (L-NAME) or the cyclooxygenase inhibitor indomethacin. The plasma nitrite/nitrate concentrations were checked via a Griess reaction. The cyclic GMP content in the thoracic aortic rings was measured by radioimmunoassay and the endothelial nitric oxide synthase (eNOS) mRNA expression was assessed by real time PCR. Result: The mean infarct size (%) in the rats with AMI was $21.3{\pm}0.62%$. The heart rate and the systolic and diastolic blood pressure were not significantly changed in the AMI rats. The sensitivity of the contractile response to PE and KCl was significantly decreased in both the E(+) and E(-) aortic rings of the AMI group (p<0.05). L-NAME completely reversed these contractile responses whereas indomethacin did not (p<0.05). Moreover, the sensitivity of the relaxation response to Ach was also significantly decreased in the AMI group (p<0.05). The plasma nitrite and nitrate content (p<0.05), the basal cGMP content (p<0.05) and the eNOS mRNA expression (p=0.056) in the AMI rats were increased as compared with the SHAM group. Conclusion: Our findings indicate that the increased eNOS activity and the up-regulation of the NO-cGMP pathway can be attributed to the decreased contractile or relaxation response in the rat thoracic aorta 3 days after AMI.

• The Journal of Internal Korean Medicine
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• v.27 no.1
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• pp.276-287
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• 2006

Background & Objective : The herbal medicine Sojukgunbihwan granule has been used for the treatment of functional dyspepsia, generally categorized as a gastric dysmotility disease. However, its mechanisms are not yet well known. Therefore, the effects of Sojukgunbihwan granules on gastric motility in rats was investigated. Methods : The myoelectrical activity of the gastric smooth muscle was recorded by a bipolar electrode placed at the gastric antrum of rats. The contractile waves were measured for 30 minutes before and after intragastric administration of each solution(normal saline, Pyungwisan 40mg/kg, Sojukgunbihwan granules 60mg/kg) and expressed as the motility index. Gastric emptying was measured by the number of glass beads expelled from the stomach(containing one hundred 1mm glass beads) within an hour after glass beads and test drugs(normal saline, Pyungwisan 40mg/kg, Pyungwisan 120mg/kg, Sojukgunbihwan granules 60mg/kg, Sojukgunbihwan granules 180mg/kg) were administered. In another series of experiments to evaluate the mechanisms of Sojukgunbihwan granules under delayed conditions, the rats were treated with atropine sulfate(1 mg/kg, s.c.), cisplatin(10mg/kg, i.p.), and NAME($N^G$-nitro-L-arginine methyl ester, 75mg/kg, s.c.) respectively. Results : Intragastric administration of Sojukgunbihwan granules increased the myoelectrical activity significantly, gastric motility index rose 25%, and gastric emptying of glass beads was significantly enhanced over a period of 60minutes. Under the delayed gastric emptying induced by atropine sulfate, cisplatin, and NAME, Sojukgunbihwan granules aggravated gastric emptying in the atropine sulfate($5.71{\pm}3.45\;vs\;3.71{\pm}4.42$) and cisplatin($13.86{\pm}3.53\;vs\;5.14{\pm}5.05$, p<0.01) treated groups, but enhanced gastric emptying in the NAME treated group($5.00{\pm}3.21\;vs\;11.71{\pm}5.65$, p<0.05). Conclusions : Results suggest that Sojukgunbihwan granules stimulate gastric motility through cholinergic and 5-hydroxytryptamine 3 receptors. Results are indicative of Sojukgunbihwan as an especially effective remedy in dysmotility-like functional dyspepsia with impaired reservoir functions such as gastric adaptive relaxation.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.5
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• pp.411-418
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• 2014

Vascular remodelling is an adaptive mechanism, which counteracts pressure changes in blood circulation. Nicotine content in cigarette increases the risk of hypertension. The exact relationship between nicotine and vascular remodelling still remain unknown. Current study was aimed to determine the effect of clinically relevant dosage of nicotine (equivalent to light smoker) on aortic reactivity, oxidative stress markers and histomorphological changes. Twelve age-matched male Sprague-Dawley rats were randomly divided into two groups, i.e.: normal saline as control or 0.6 mg/kg nicotine for 28 days (i.p., n=6 per group). On day-29, the rats were sacrificed and the thoracic aorta was dissected immediately for further studies. Mean arterial pressure (MAP) and pulse pressure (PP) of nicotine-treated vs. control were significantly increased (p<0.05). Nicotine-treated group showed significant (p<0.05) increase tunica media thickness, and decrease in lumen diameter, suggesting vascular remodelling which lead to prior hypertension state. The phenylephrine (PE)-induced contractile response in nicotine group was significantly higher than control group ($ED_{50}=1.44{\times}10^5M$ vs. $4.9{\times}10^6M$) (p<0.05~0.001). However, nicotine-treated rat showed significantly lower endothelium-dependent relaxation response to acetylcholine (ACh) than in control group ($ED_{50}=6.17{\times}10^7M$ vs. $2.82{\times}10^7M$) (p<0.05), indicating loss of primary vascular function. Malondialdehyde (MDA), a lipid peroxidation marker was significantly higher in nicotine group. Superoxide dismutase (SOD) enzymatic activity and glutathione (GSH) were all reduced in nicotine group (p<0.05) vs. control, suggesting nicotine induces oxidative imbalance. In short, chronic nicotine administration impaired aortic reactivity, probably via redox imbalance and vascular remodelling mechanism.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.2
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• pp.242-247
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• 1997

A flavone glycoside was separated from the aerial part of Circium japonicum var ussuriense Kitamura and the effect on cardiovascular system was investigated. The cadiovascular contractility of this compound was observed in the artria and aortae from normal rats. It increased the spontancous beat in right atria and the contractile force in left atria, and caused the contraction of thoracic aortae. For the blood pressure, it had ascending effect. The effective component, which acted on stimulation and contraction in the artria and aortae of rats was fractionated with n-BuOH, separated and identified by column chromatography, UV, IR, $^1H-NMR$ and $^{13}C-NMR$. The chemical structure for this component was determined to be $hispidulin-7-{\alpha}-rhamnopyranosyl(1{\rightarrow}2)-{\beta}-D-glucopyranoside$.

• The Korean Journal of Physiology
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• v.17 no.2
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• pp.103-107
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• 1983

This experiment was undertaken to see whether dopamine has any effect on a uterine function and whether the uterus has a dopamine receptor. We used 14 female rats in the diestrus state which was identified by a vaginal smear. Under ether anesthesia, 3 pieces(1 cm length) from each side of the uterus were dissected out and mounted in 3 tissue chambers (4 cm diameter, 10 cm height) that contained Krebs-Ringer solution. The solution was continuously aerated with 95% $O_2$ containing 5% $CO_2$ and kept $37^{\circ}C$ consistantly during the whole experimental period. The spontaneous contractile activity of the isolated uterus was recorded using a force transducer. After a recovery period of 15 min in the chamber, the following experiments were carried out. In 7 rats, each piece of the uterus was received dopamine at concentrations of $10^{-4}$, $10^{-5}$ or $10^{-6}\;M$ for 10 min and then followed by domperidone at a concentration of $10^{-5}\;M$. In another 7 rats, each piece was received domperidone, a specific peripheral dopamine receptor antagonist, was administered at a concentration of $10^{-5}\;M$ for 5 min prior to dopamine at concentrations of $10^{-4}$, $10^{-5}$, or $10^{-6}\;M$. Dopamine inhibited the spontaneous uterine contraction dose-dependently (r=0.99, p<.01). The inhibited contractility by dopomine was significantly (P<.05) resumed by post-treatment of domperidone. Pre-treatment of domperidone also blocked significantly(p<.05) the inhibitory effect of dopamine. It is concluded from these results that dopamine has inhibitory role upon the spontaneous uterine contraction of the rat in the diestrus state and domperidone antagonized the inhibitory effect of dopamine. These results suggest strongly that dopamine may exert the inhibitory effect via the dopamine receptor in the rat uterus.