• The Korean Journal of Physiology and Pharmacology
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• 제9권2호
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• pp.87-94
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• 2005

It is not clear whether $Ca^{2+}-induced$ $Ca^{2+}$ release from the sarcoplasmic reticulum (SR) is involved in the regulation of atrial natriuretic peptide (ANP) release. Previously, we have shown that nifedipine increased ANP release, indicating that $Ca^{2+}$ entry via voltage-gated L-type $Ca^{2+}$ channel activation decreases ANP release. The purpose of the present study was two-fold: to define the role of SR $Ca^{2+}$ release in the regulation of ANP release and whether $Ca^{2+}$ entry via L-type $Ca^{2+}$ channel is prerequisite for the SR-related effect on ANP release. Experiments were performed in perfused beating rabbit atria. Ryanodine, an inhibitor of SR $Ca^{2+}$ release, increased atrial myocytic ANP release ($8.69{\pm}3.05$, $19.55{\pm}1.09$, $27.31{\pm}3.51$, and $18.91{\pm}4.76$% for 1, 2, 3, and $6{\mu}M$ ryanodine, respectively; all P<0.01) with concomitant decrease in atrial stroke volume and pulse pressure in a dose-dependent manner. In the presence of thapsigargin, an inhibitor of SR $Ca^{2+}$ pump, ryanodine-induced increase in ANP release was not observed. Thapsigargin attenuated ryanodine-induced decrease in atrial dynamic changes. Blockade of L-type $Ca^{2+}$ channel with nifedipine abolished ryanodine-induced increase in ANP release ($0.69{\pm}5.58$% vs. $27.31{\pm}3.51$%; P＜0.001). In the presence of thapsigargin and ryanodine, nifedipine increased ANP release and decreased atrial dynamics. These data suggest that $Ca^{2+}$-induced $Ca^{2+}$ release from the SR is inversely involved in the regulation of atrial myocytic ANP release.

• The Korean Journal of Physiology and Pharmacology
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• 제15권1호
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• pp.53-59
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• 2011

The secretion of insulin from pancreatic ${\beta}$-cells is triggered by the influx of $Ca^{2+}$ through voltage-dependent $Ca^{2+}$ channels. The resulting elevation of intracellular calcium ($[Ca^{2+}]_i$) triggers additional $Ca^{2+}$ release from internal stores. Less well understood are the mechanisms involved in $Ca^{2+}$ mobilization from internal stores after activation of $Ca^{2+}$ influx. The mobilization process is known as calcium-induced calcium release (CICR). In this study, our goal was to investigate the existence of and the role of caffeine-sensitive ryanodine receptors (RyRs) in a rat pancreatic ${\beta}$-cell line, INS-1 cells. To measure cytosolic and stored $Ca^{2+}$, respectively, cultured INS-1 cells were loaded with fura-2/AM or furaptra/AM. $[Ca^{2+}]_i$ was repetitively increased by caffeine stimulation in normal $Ca^{2+}$ buffer. However, peak $[Ca^{2+}]_i$ was only observed after the first caffeine stimulation in $Ca^{2+}$ free buffer and this increase was markedly blocked by ruthenium red, a RyR blocker. KCl-induced elevations in $[Ca^{2+}]_i$ were reduced by pretreatment with ruthenium red, as well as by depletion of internal $Ca^{2+}$ stores using cyclopiazonic acid (CPA) or caffeine. Caffeine-induced $Ca^{2+}$ mobilization ceased after the internal stores were depleted by carbamylcholine (CCh) or CPA. In permeabilized INS-1 cells,$Ca^{2+}$ release from internal stores was activated by caffeine, $Ca^{2+}$, or ryanodine. Furthermore, ruthenium red completely blocked the CICR response in perrneabilized cells. RyRs were widely distributed throughout the intracellular compartment of INS-1 cells. These results suggest that caffeine-sensitive RyRs exist and modulate the CICR response from internal stores in INS-1 pancreatic ${\beta}$-cells.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.229-239
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• 2009

The aim of the present study was to examine the effect of provinol, which is a mixture of polyphenolic compounds from red wine, on the secretion of catecholamines (CA) from isolated perfused rat adrenal medulla, and to elucidate its mechanism of action. Provinol (0.3 ${\sim}$ 3 ${\mu}g/ml$) perfused into an adrenal vein for 90 min dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic $N_N$ receptor agonist, 100 ${\mu}M$) and McN-A-343 (a selective muscarinic $M_1$ receptor agonist, 100 ${\mu}M$). Provinol itself did not affect basal CA secretion. Also, in the presence of provinol (1 ${\mu}g/ml$), the secretory responses of CA evoked by Bay-K-8644 (a voltage-dependent L-type dihydropyridine $Ca^{2+}$ channel activator, 10 ${\mu}M$), cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10 ${\mu}M$) and veratridine (an activator of voltage-dependent $Na^+$ channels, 10 ${\mu}M$) were significantly reduced. Interestingly, in the simultaneous presence of provinol (1 ${\mu}g/ml$) plus L-NAME (a selective inhibitor of NO synthase, 30 ${\mu}M$), the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclpiazonic acid recovered to the considerable extent of the corresponding control secretion in comparison with the inhibition of provinol-treatment alone. Under the same condition, the level of NO released from adrenal medulla after the treatment of provinol (3 ${\mu}g/ml$) was greatly elevated in comparison to its basal release. Taken together, these data demonstrate that provinol inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the perfused rat adrenal medulla. This inhibitory effect of provinol seems to be exerted by inhibiting the influx of both calcium and sodium into the rat adrenal medullary cells along with the blockade of $Ca^{2+}$ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of nitric oxide synthase.

• 유통과학연구
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• 제10권10호
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• pp.45-57
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• 2012

Purpose - This study was conducted to evaluate service quality, perceived value, and satisfaction in the performing arts in order to establish a system of relationships that predicts repurchase intention, which increasingly needs to be studied as the domestic performing arts market grows. Research design, data, and methodology - Another purpose of this study is to identify 'work-related factors' and 'performing-arts-related factors' in the performing arts industry, and to observe the influence of the core SQ factors expected to influence audiences' purchase intentions through perceived value and customer satisfaction. The empirical study to test the hypothesis was based on a review of the literature and employed the survey method; data were collected from a total of 500 audience members. Results - The major results of the analysis are as follows. First, in terms of quality factors affecting perceived value, literary quality, level, professionalism, and musical quality were shown to have a significant influence as key factors from the performing arts perspective, while reliability, convenience, and related costs were indicated to exert a significant influence as additional factors related to work. Secondly, the quality factors with a significant influence on customer satisfaction were literary quality, professionalism, and musical quality, which were shown to have a significant influence from the performing arts perspective, while only reliability was indicated to exert a significant influence on work-related factors. Third, perceived value was shown to have a strong positive (+) influence on customer satisfaction, with both perceived value and customer satisfaction exerting a significant influence on the revisit intention. Finally, according to the results a difference analysis with demographic variables, viewing variables as moderating variables, differences according to gender were indicated in the influence of literary value and lel on perceived value, and in the influence of convenience and professionalism on customer satisfaction as well. Also, in terms of the influence of perceived value on customer satisfaction, males were found to be more influenced than females. Conclusions - Based on the above results, the suggested implications of the present study are as follows. First, through the consideration of not only the crucial work perspective in performing arts services, which has been inadequate in the past, but the additional performance-related level, the previously unevenly distributed viewpoints were expanded for application. Second, in verifying the relationship between expanded quality factors and the factors that determine consumer behavior while simultaneously considering key factors and additional related factors, work-related service quality factors were shown to exert a stronger influence on perceived value and customer satisfaction than performance-related factors. Third, for service factors related to performance, the reliability factor exerts an influence on perceived value and customer satisfaction, requiring that a performance planner secure and manage diverse channels to immediately support customer requests in providing performance theater services.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.140-140
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• 2017

Nutritious and functional foods from crop have received great attention in recent years. Colored-grain wheat contains high phenolic compound and a large number of flavonoid. The anthocyanin and polyphenolic synthesis and accumulation is generally stimulated in response to biotic or abiotic stresses. Here, we analyzed genome wide transcripts in seedling of colored-grain wheat response to ABA and PEG treatment. About 900 and 1500 transcripts (p-value < 0.05) from ABA and PEG treatment were aligned to IWGSC1+popseq DB which is composed of over 110,000 transcripts including 100,934 coding genes. NR protein sequences of Poaceae from NCBI and protein sequence of transcription factors originated from 83 species in plant transcription factor database v3.0 were used for annotation of putative transcripts. Gene ontology analysis were conducted and KEGG mapping was performed to show expression pattern of biosynthesis genes related in flavonoid, isoflavonoid, flavons and anthocyanin biopathway. DroughtDB (http://pgsb.helmholtz-muenchen.de/droughtdb/) was used for detection of DEGs to explain that physiological and molecular drought avoidance by drought tolerance mechanisms. Drought response pathway, such as ABA signaling, water and ion channels, detoxification signaling, enzymes of osmolyte biosynthesis, phospholipid metabolism, signal transduction, and transcription factors related DEGs were selected to explain response mechanism under water deficit condition. Anthocyanin, phenol compound, and DPPH radical scavenging activity were measured and antioxidant activity enzyme assays were conducted to show biochemical adaptation under water deficit condition. Several MYB and bHLH transcription factors were up-regulated in both ABA and PEG treated condition, which means highly expressed MYB and bHLH transcription factors enhanced the expression of genes related in the biosynthesis pathways of flavonoids, such as anthocyanin and dihydroflavonols in colored wheat seedlings. Subsequently, the accumulation of total anthocyanin and phenol contents were observed in colored wheat seedlings, and antioxidant capacity was promoted by upregulation of genes involved in maintaining redox state and activation of antioxidant scavengers, such as CAT, APX, POD, and SOD in colored wheat seedlings under water deficit condition. This work may provide valuable and basic information for further investigation of the molecular responses of colored-grain wheat to water deficit stress and for further gene-based studies.

• The Korean Journal of Physiology and Pharmacology
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• 제5권5호
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• pp.397-405
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• 2001

The ryanodine receptor, a $Ca^{2+}$ release channel of the sarcoplasmic reticulum (SR), is responsible for the rapid release of $Ca^{2+}$ that activates cardiac muscle contraction. In the excitation-contraction coupling cascade, activation of SR $Ca^{2+}$ release channel is initiated by the activity of sarcolemmal $Ca^{2+}$ channels, the dihydropyridine receptors. Previous study showed that the relaxation defect of diabetic heart was due to the changes of the expressional levels of SR $Ca^{2+}$ATPase and phospholamban. In the diabetic heart contractile abnormalities were also observed, and one of the mechanisms for these changes could include alterations in the expression and/or activity levels of various $Ca^{2+}$ regulatory proteins involving cardiac contraction. In the present study, underlying mechanisms for the functional derangement of the diabetic cardiomyopathy were investigated with respect to ryanodine receptor, and dihydropyridine receptor at the transcriptional and translational levels. Quantitative changes of ryanodine receptors and the dihydropyridine receptors, and the functional consequences of those changes in diabetic heart were investigated. The levels of protein and mRNA of the ryanodine receptor in diabetic rats were comparable to these of the control. However, the binding capacity of ryanodine was significantly decreased in diabetic rat hearts. Furthermore, the reduction in the binding capacity of ryanodine receptor was completely restored by insulin. This result suggests that there were no transcriptional and translational changes but functional changes, such as conformational changes of the $Ca^{2+}$ release channel, which might be regulated by insulin. The protein level of the dihydropyridine receptor and the binding capacity of nitrendipine in the sarcolemmal membranes of diabetic rats were not different as compared to these of the control. In conclusion, in diabetic hearts, $Ca^{2+}$ release processes are impaired, which are likely to lead to functional derangement of contraction of heart. This dysregulation of intracellular $Ca^{2+}$ concentration could explain for clinical findings of diabetic cardiomyopathy and provide the scientific basis for more effective treatments of diabetic patients. In view of these results, insulin may be involved in the control of intracellular $Ca^{2+}$ in the cardiomyocyte via unknown mechanism, which needs further study.

• 대한약리학회지
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• 제32권2호
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• pp.189-199
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• 1996

Myocardial ${\alpha}_1-adrenoceptors$ have been shown to mediate a biphaslc inotropic response that was characterized by a transient decline followed by a sustained increasing phase in guinea pig ventricular muscle. Recently one group reported that an ${\alpha}_1-adrenoceptors-induced$ intracellular $Na^+$ decrease is linked to fast $Na^+$ channel inhibition and another group reported that it is linked to $Na^+$-$K^+$ pump activation by ${\alpha}_{1b}-adrenoceptors$. But until now, its mechanism is not clear. Therefore, to see whether the $Na^+$channel or $Na^+-K^+$ pump is related to a decrease in intracellular $Na^+$ activity and/or the negative inotropic response, and which ${\alpha}_1-adrenoceptor$ subtype was involved in the decrease in intracellular $Na^+$activity by phenylephrine, we used conventional and sodium selective microelectrodes, and tension transducer to determine the effects of ${\alpha}_1-adrenergic$ stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force in guinea pig ventricular muscles. $10^{-5}$ M Phenylephrine produced a slight hyperpolarization of the diastolic membrane potential, a decrease or increase in $a_N^i_a$, and a biphasic inotropic response. The negative inotropic response accompanied by a decrease in intracellular $Na^+$activity, whereas in muscles showing a remarkable positive inotropic response without initial negative inotropic effect was accompanied by an increase in intracellular $Na^+$ activity. The decrease in intracellular $Na^+$ activity was apparently inhibited by WB4101, an antagonist of the ${\alpha}_{1a}-adrenoceptors$. The decrease in intracellular $Na^+$ activity caused by phenylephrine was not abolished or reduced by a block of the fast $Na^+$ channels. $V_{max}$ also was not affected by phenylephrine. Phenylephrine produced an increase in intracellular $Na^+$ activity in the presence of a high concentration of extracellular $Ca^{2+}$ (in quiescent muscle) or phorbol dibutyrate, a protein kinase C activator(in beating muscle). These suggest that the ${\alpha}_{1a}-adrenoceptors-mediated$ decrease in intracellular $Na^+$ activity may be related to the protein kinase C.

• 대한화장품학회지
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• 제44권1호
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• pp.73-79
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• 2018

일차 섬모(primary cilia)는 세포에서 안테나처럼 돌출되어 나온 기관인데, 외부 자극에 반응할 수 있는 각종 수용체와 채널, 신호 전달 인자들을 가지고 있다. 피부는 자외선, 온도, 습도, 중력, 장력 등 외부 환경에 반응하여 멜라닌이나 콜라겐을 만들고 피부 장벽을 형성한다. 피부에서는 일차 섬모가 없으면 헤어의 생성이나 각질의 분화가 억제된다는 보고가 있다. 또한 피부 색소 생성과 관련하여서는 일차 섬모가 sonic hedgehog-smoothened-GLI2 신호 전달에 의해 활성화되면 멜라닌 생성이 억제된다는 것이 알려져 있다. 피부가 자외선을 받으면 멜라닌 생성 호르몬의 양이 증가하고 멜라닌 생성 호르몬은 멜라닌 생성 세포 내 cAMP의 양을 증가시켜 멜라닌 생성 효소의 발현을 높인다. 이에 멜라닌 생성 호르몬과 세포 내 cAMP의 양을 증가시키는 물질을 처리하여 멜라닌 생성을 높였을 때 일차 섬모의 변화를 확인한 결과 일차 섬모가 감소하는 것을 확인하였다. 또한 기존 미백 원료인 유용성 감초 추출물(an ethanol extract of Glycyrrhiza glabra (EGG) root)과 Melasolv (3,4,5-trimethoxy cinnamate thymol ester (TCTE))가 일차 섬모의 발현을 증가시키고 멜라닌 생성 효소인 tyrosinase의 발현을 억제함을 확인할 수 있었다. 따라서 일차 섬모를 조절할 수 있다면 피부 색소 침착을 효과적으로 조절할 수 있을 것이다.

• Journal of Ginseng Research
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• 제39권2호
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• pp.169-177
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• 2015

Background: Ginsenoside Rd (GSRd), one of the most abundant ingredients of Panax ginseng, protects the heart via multiple mechanisms including the inhibition of $Ca^{2+}$ influx.We intended to explore the effects of GSRd on L-type $Ca^{2+}$ current ($I_{Ca,L}$) and define the mechanism of the suppression of $I_{Ca,L}$ by GSRd. Methods: Perforated-patch recording and whole-cell voltage clamp techniques were applied in isolated rat ventricular myocytes. Results: (1) GSRd reduced $I_{Ca,L}$ peak amplitude in a concentration-dependent manner [half-maximal inhibitory concentration $(IC_{50})=32.4{\pm}7.1{\mu}mol/L$] and up-shifted the current-voltage (I-V) curve. (2) GSRd ($30{\mu}mol/L$) significantly changed the steady-state activation curve of $I_{Ca,L}$ ($V_{0.5}:-19.12{\pm}0.68$ vs. $-6.26{\pm}0.38mV$; n = 5, p < 0.05) and slowed down the recovery of $I_{Ca,L}$ from inactivation [the time content (${\zeta}$) from 91 ms to 136 ms, n = 5, p < 0.01]. (3) A more significant inhibitive effect of GSRd ($100{\mu}mol/L$) was identified in perforated-patch recording when compared with whole-cell recording [$65.7{\pm}3.2%$ (n = 10) vs. $31.4{\pm}5.2%$ (n = 5), p < 0.01]. (4) Pertussis toxin ($G_i$ protein inhibitor) completely abolished the $I_{Ca,L}$ inhibition induced by GSRd. There was a significant difference in inhibition potency between the two cyclic adenosine monophosphate elevating agents (isoprenaline and forskolin) prestimulation [$55{\pm}7.8%$ (n = 5) vs. $17.2{\pm}3.5%$ (n = 5), p < 0.01]. (5) 1H-[1,2,4]Oxadiazolo[4,3-a]-quinoxalin-1-one (a guanylate cyclase inhibitor) and N-acetyl-$\small{L}$-cysteine (a nitric oxide scavenger) partly recovered the $I_{Ca,L}$ inhibition induced by GSRd. (6) Phorbol-12-myristate-13-acetate (a protein kinase C activator) and GF109203X (a protein kinase C inhibitor) did not contribute to the inhibition of GSRd. Conclusion: These findings suggest that GSRd could inhibit $I_{Ca,L}$ through pertussis toxin-sensitive G protein ($G_i$) and a nitric oxide-cyclic guanosine monophosphate-dependent mechanism.

• The Korean Journal of Physiology and Pharmacology
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• 제4권1호
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• pp.33-40
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• 2000

This study was designed to clarify the mechanism of the inhibitory action of a nitric oxide (NO) donor, 3-morpholino-sydnonimine (SIN-1), on contraction, cytosolic $Ca^{2+}$ level $([Ca^{2+}]_i)$ and ionic currents in guinea-pig ileum. SIN-1 $(0.01{\sim}100\;{\mu}M)$ inhibited 25 mM KCl- or histamine $(10\;{\mu}M)-induced$ contraction in a concentration-dependent manner. SIN-1 reduced both the 25 mM KCl- and the histamine-stimulated increases in muscle tension in parallel with decreased $[Ca^{2+}]_i.$ Using the patch clamp technique with a holding potential of -60 mV, SIN-1 $(10\;{\mu}M)$ decreased peak Ba currents $(I_{Ba})$ by $30.9{\pm}5.4%$ (n=6) when voltage was stepped from -60 mV to +10 mV and this effect was blocked by ODQ $(1\;{\mu}M),$ a soluble guanylyl cyclase inhibitor. Cu/Zn SOD (100 U/ml), the free radical scavenger, had little effect on basal $I_{Ba},$ and SIN-1 $(10\;{\mu}M)$ inhibited peak $I_{Ba}$ by $32.4{\pm}5.8%$ (n=5) in the presence of Cu/Zn SOD. In a cell clamped at a holding-potential of -40 mV, application of $10\;{\mu}M$ histamine induced an inward current. The histamine-induced inward current was markedly and reversibly inhibited by $10\;{\mu}M$ SIN-1, and this effect was abolished by ODQ $(1\;{\mu}M).$ In addition, SIN-1 markedly increased the depolarization-activated outward $K^+$ currents in the all potential ranges. We concluded that SIN-1 inhibits smooth muscle contraction mainly by decreasing $[Ca^{2+}]_i$ resulted from the inhibition of L-type $Ca^{2+}$ channels and the inhibition of nonselective cation currents and/or by the activation of $K^+$ currents via a cGMP-dependent pathway.