Signaling Pathway of Lysophosphatidic Acid-Induced Contraction in Feline Esophageal Smooth Muscle Cells

Yun Sung Nam,Jung Sook Suh,Hyun Ju Song,Uy Dong Sohn 대한생리학회-대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.2

Lysolipids such as LPA, S1P and SPC have diverse biological activities including cell proliferation, differentiation, and migration. We investigated signaling pathways of LPA-induced contraction in feline esophageal smooth muscle cells. We used freshly isolated smooth muscle cells and permeabilized cells from cat esophagus to measure the length of cells. Maximal contraction occurred at 10⁻⁶ M and the response peaked at 30s. To identify LPA receptor subtypes in cells, western blot analysis was performed with antibodies to LPA receptor subtypes. LPA1 and LPA3 receptor were detected at 50 kDa and 44 kDa. LPA-induced contraction was almost completely blocked by LPA receptor (1/3) antagonist KI16425. Pertussis toxin (PTX) inhibited the contraction induced by LPA, suggesting that the contraction is mediated by a PTX-sensitive G protein. Phospholipase C (PLC) inhibitors U73122 and neomycin, and protein kinase C (PKC) inhibitor GF109203X also reduced the contraction. The PKC-mediated contraction may be isozyme-specific since only PKCՅ antibody inhibited the contraction. MEK inhibitor PD98059 and JNK inhibitor SP600125 blocked the contraction. However, there is no synergistic effect of PKC and MAPK on the LPA-induced contraction. In addition, RhoA inhibitor C3 exoenzyme and ROCK inhibitor Y27632 significantly, but not completely, reduced the contraction. The present study demonstrated that LPA-induced contraction seems to be mediated by LPA receptors (1/3), coupled to PTX-sensitive G protein, resulting in activation of PLC, PKC-Յ pathway, which subsequently mediates activation of ERK and JNK. The data also suggest that RhoA/ROCK are involved in the LPA-induced contraction.

국어 후음 계열의 축약 현상에 대하여

배영환 개신어문학회 2015 개신어문연구 Vol.40 No.-

The purpose of this study is to examine a few issues associated with the contraction phenomenon in Korean. In Korean, contraction can be considered to be the phenomenon that two phonemes are combined to be a single phoneme. It is the phenomenon that the number of phonemes is reduced in the process of phonological changes. Of phenomena treated as the contraction in the previous discussion, a phonological phenomenon difficult to be regarded as contraction and phenomenon newly regarded as contraction were reviewed. In some cases, it is not easy to describe the scope of contraction and process of contraction with aspiration, the representative phonological phenomenon of contraction. With regard to the scope of contraction, so called the contraction phenomenon does not belong to the category of contraction in the strict sense. They also included things not easy to be explained only by glide formation or phonological aspects. And of the problems on the process of contraction, when ‘ㅈ’ etc. come in front of ‘ㅎ’ as shown in ‘[ichida]’, it is not easy to explain that it has been aspirated after going through syllable-final plain stops or ‘ㅈ’ and ‘ㅎ’ have been directed contracted. A phonological phenomenon that can be newly regarded as contraction is related to ‘ㆆ’. ‘ㆆ’ can be considered to be a phoneme appropriate to describe the irregular verbs of Korean and be understood in terms of showing the feasibility of phonological skills. According to the utilization aspect shown in ‘Jikko, Jieuni, Jieo’, it is difficult to explain that the utilization aspect of the previous period has been fossilized into modern Korean. Therefore, it is reasonable to recognize ‘ㆆ’ and regard it as the resulting contraction. ‘ㆆ’ can be considered as an element of glottalizing a following ending immediately without being changed or neutralized into ‘ㄷ’. By considering so, there is an advantage that it can be described in parallel with the aspiration phenomenon in which ‘ㅎ’ is shown.

Signaling Pathway of Lysophosphatidic Acid-Induced Contraction in Feline Esophageal Smooth Muscle Cells

남윤성,서정숙,송현주,손의동 대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.2

Lysolipids such as LPA, S1P and SPC have diverse biological activities including cell proliferation,differentiation, and migration. We investigated signaling pathways of LPA-induced contraction in feline esophageal smooth muscle cells. We used freshly isolated smooth muscle cells and permeabilized cells from cat esophagus to measure the length of cells. Maximal contraction occurred at 10−6 M and the response peaked at 30s. To identify LPA receptor subtypes in cells, western blot analysis was performed with antibodies to LPA receptor subtypes. LPA1 and LPA3 receptor were detected at 50 kDa and 44kDa. LPA-induced contraction was almost completely blocked by LPA receptor (1/3) antagonist KI16425. Pertussis toxin (PTX) inhibited the contraction induced by LPA, suggesting that the contraction is mediated by a PTX-sensitive G protein. Phospholipase C (PLC) inhibitors U73122 and neomycin, and protein kinase C (PKC) inhibitor GF109203X also reduced the contraction. The PKC-mediated contraction may be isozyme-specific since only PKCε antibody inhibited the contraction. MEK inhibitor PD98059 and JNK inhibitor SP600125 blocked the contraction. However, there is no synergistic effect of PKC and MAPK on the LPA-induced contraction. In addition, RhoA inhibitor C3exoenzyme and ROCK inhibitor Y27632 significantly, but not completely, reduced the contraction. The present study demonstrated that LPA-induced contraction seems to be mediated by LPA receptors (1/3),coupled to PTX-sensitive G protein, resulting in activation of PLC, PKC-ε pathway, which subsequently mediates activation of ERK and JNK. The data also suggest that RhoA/ROCK are involved in the LPA-induced contraction.

Signaling Pathway of Lysophosphatidic Acid-Induced Contraction in Feline Esophageal Smooth Muscle Cells

Nam, Yun Sung,Suh, Jung Sook,Song, Hyun Ju,Sohn, Uy Dong The Korean Society of Pharmacology 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.2

Lysolipids such as LPA, S1P and SPC have diverse biological activities including cell proliferation, differentiation, and migration. We investigated signaling pathways of LPA-induced contraction in feline esophageal smooth muscle cells. We used freshly isolated smooth muscle cells and permeabilized cells from cat esophagus to measure the length of cells. Maximal contraction occurred at $10^{-6}M$ and the response peaked at 30s. To identify LPA receptor subtypes in cells, western blot analysis was performed with antibodies to LPA receptor subtypes. LPA1 and LPA3 receptor were detected at 50 kDa and 44 kDa. LPA-induced contraction was almost completely blocked by LPA receptor (1/3) antagonist KI16425. Pertussis toxin (PTX) inhibited the contraction induced by LPA, suggesting that the contraction is mediated by a PTX-sensitive G protein. Phospholipase C (PLC) inhibitors U73122 and neomycin, and protein kinase C (PKC) inhibitor GF109203X also reduced the contraction. The PKC-mediated contraction may be isozyme-specific since only $PKC{\varepsilon}$ antibody inhibited the contraction. MEK inhibitor PD98059 and JNK inhibitor SP600125 blocked the contraction. However, there is no synergistic effect of PKC and MAPK on the LPA-induced contraction. In addition, RhoA inhibitor C3 exoenzyme and ROCK inhibitor Y27632 significantly, but not completely, reduced the contraction. The present study demonstrated that LPA-induced contraction seems to be mediated by LPA receptors (1/3), coupled to PTX-sensitive G protein, resulting in activation of PLC, PKC-${\varepsilon}$ pathway, which subsequently mediates activation of ERK and JNK. The data also suggest that RhoA/ROCK are involved in the LPA-induced contraction.

Dexmedetomidine-induced contraction of isolated rat aorta is dependent on extracellular calcium concentration

옥성호,배성일,심행선,손주태 대한마취통증의학회 2012 Korean Journal of Anesthesiology Vol.63 No.3

Background: Dexmedetomidine is a highly selective α2-adrenoceptor agonist that is widely used for sedation and analgesia during the perioperative period. Intravenous administration of dexmedetomidine induces transient hypertension due to vasoconstriction via the activation of the α2-adrenoceptor on vascular smooth muscle. The goal of this in vitro study is to investigate the calcium-dependent mechanism underlying dexmedetomidine-induced contraction of isolated endothelium-denuded rat aorta. Methods: Isolated endothelium-denuded rat thoracic aortic rings were suspended for isometric tension recording. Cumulative dexmedetomidine concentration-response curves were generated in the presence or absence of the following inhibitors: α2-adrenoceptor inhibitor rauwolscine; voltage-operated calcium channel blocker verapamil (5 × 10-7, 10-6 and 5 × 10-5 M); purported inositol 1,4,5-trisphosphate receptor blocker 2-aminoethoxydiphenylborate (5 × 10-6, 10-5 and 5 × 10-5 M); phospholipase C inhibitor U-73122 (10-6 and 3 × 10-6 M); and store-operated calcium channel inhibitor gadolinium chloride hexahydrate (Gd3+; 5 × 10-6 M). Dexmedetomidine concentration-response curves were also generated in low calcium concentrations (1 mM) and calcium-free Krebs solution. Results: Rauwolscine, verapamil, and 2-aminoethoxydiphenylborate attenuated dexmedetomidine-induced contraction in a concentration-dependent manner. Low calcium concentrations attenuated dexmedetomidine-induced contraction, and calcium-free Krebs solution nearly abolished dexmedetomidine-induced contraction. However, U-73122 and Gd3+ had no effect on dexmedetomidine-induced contraction. Conclusions: Taken together, these results suggest that dexmedetomidine-induced contraction is primarily dependent on extracellular calcium concentrations that contribute to calcium influx via voltage-operated calcium channels of isolated rat aortic smooth muscle. Dexmedetomidine-induced contraction is mediated by α2-adrenoceptor stimulation. Dexmedetomidine-induced contraction appears to be partially mediated by calcium release from the sarcoplasmic reticulum. Background: Dexmedetomidine is a highly selective α2-adrenoceptor agonist that is widely used for sedation and analgesia during the perioperative period. Intravenous administration of dexmedetomidine induces transient hypertension due to vasoconstriction via the activation of the α2-adrenoceptor on vascular smooth muscle. The goal of this in vitro study is to investigate the calcium-dependent mechanism underlying dexmedetomidine-induced contraction of isolated endothelium-denuded rat aorta. Methods: Isolated endothelium-denuded rat thoracic aortic rings were suspended for isometric tension recording. Cumulative dexmedetomidine concentration-response curves were generated in the presence or absence of the following inhibitors: α2-adrenoceptor inhibitor rauwolscine; voltage-operated calcium channel blocker verapamil (5 × 10-7, 10-6 and 5 × 10-5 M); purported inositol 1,4,5-trisphosphate receptor blocker 2-aminoethoxydiphenylborate (5 × 10-6, 10-5 and 5 × 10-5 M); phospholipase C inhibitor U-73122 (10-6 and 3 × 10-6 M); and store-operated calcium channel inhibitor gadolinium chloride hexahydrate (Gd3+; 5 × 10-6 M). Dexmedetomidine concentration-response curves were also generated in low calcium concentrations (1 mM) and calcium-free Krebs solution. Results: Rauwolscine, verapamil, and 2-aminoethoxydiphenylborate attenuated dexmedetomidine-induced contraction in a concentration-dependent manner. Low calcium concentrations attenuated dexmedetomidine-induced contraction, and calcium-free Krebs solution nearly abolished dexmedetomidine-induced contraction. However, U-73122 and Gd3+ had no effect on dexmedetomidine-induced contraction. Conclusions: Taken together, these results suggest that dexmedetomidine-induced contraction is primarily dependent on extracellular calcium concentrations that contribute to calcium influx via voltage-operated calcium channels of isolated rat aortic smooth muscle. Dexmedetomidine-induced contraction is mediated by α2-adrenoceptor stimulation. Dexmedetomidine-induced contraction appears to be partially mediated by calcium release from the sarcoplasmic reticulum.

KCl과 phenylephrine에 의한 대동맥 수축에서 Ca2+ 길항제와 protein kinase 억제제들의 비교 효과

심상수(Sang Soo Sim),문성원(Sung Won Moon),이윤혜(Yun Hye Lee),이정근(Jung Keun Lee),김현준(Hyun Jun Kim),박진형(Jin Hyoung Park),이준한(June Han Lee),조중형(Jung Hyung Cho),김창종(Chang Jong Kim) 대한약학회 1999 약학회지 Vol.43 No.5

To investigate the difference of contractile mechanism between KCl and phenylephrine-induced contraction, we observed effects of Ca2+ antagonists and protein kinase inhibitors on aorta contraction of rats. Verapamil dose-dependently inhibited the contraction induced by KCl and pheylephrine, the inhibitory effect of verapamil was more potent in KCl-induced contraction than phenylephrine-induced contraction. Econazole and TMB-8 significantly inhibited KCl-induced contraction but did not inhibit phenylephrine-induced contraction. Staurosporine dose-dependently inhibited both KCl and phenylephrine-induced contraction. Genistein and calmodulin antagonists (W-7 and trifluoperazine) also inhibited both contraction in a dose dependent manner. However, the inhibitory effects of genistein and calmodulin antagonists were more potent in pheylephrine-induced contraction than KCl-induced contraction. These results suggest that involvements of Ca2+ channel and protein kinase in rat aorta contraction were dependent on agonist causing aort smooth muscle contraction.

코퍼스 기반 중학교 영어 교과서 be 동사 부정 축약 분석

강혜선 ( Kang Hye-sun ),김민경 ( Kim Minkyung ),신창원 ( Shin Changwon ) 글로벌영어교육학회(구 호남영어교육학회) 2019 Studies in English education Vol.24 No.1

When be-verb negation is contracted, either verb contraction or negative contraction can be selected, based on the types of preceding subjects. Thus, a pronoun subject tends to be with verb contraction more frequently (e.g. She’s not/They’re not), while a full noun subject is more likely to occur with negative contraction (e.g. The classroom isn’t). In this regard, the current study aims to investigate if middle school English textbooks provide sufficient examples of English native speakers’ preference in using be-verb negative contraction. To this end, a small corpus was compiled, comprising all the listening materials from 14 middle school English textbooks. From this corpus, all the sentences including verb contraction and negative contraction each were extracted using a concordancer program to see what type of subject each contraction form occurs with more frequently. The results of this analysis showed that when the subject is a pronoun, verb contraction is favored over negative contraction, whereas negative contraction is more likely to be with a full noun phrase, suggesting that the English textbook present language input similar to English native speakers’ preference in using be-verb negative contraction.

Phorbol Ester-Induced Periodic Contraction in Isolated Rabbit Jugular Vein

Ryu, Jae-Cheol,Jung, Dong-Keun,Lee, Sang-Ho The Korean Physiological Society 1995 대한생리학회지 Vol.29 No.2

The present study was conducted to evaluate the effect of phorbol 12,13-dibutyrate (PDBu) on the contraction of rabbit jugular vein in vitro. PDBu concentrations of greater than 10 nM induced a periodic contraction which was composed of rapid contraction, plateau and slow relaxation. The frequency of periodic contraction increased as PDBu concentration increased. The PDBu-induced contraction was inhibited by staurosporine (100 nM), it was not changed by tetrodotoxin $(1\;{\mu}M).$ In $Ca^{2+}$-free medium, PDBu induced a sustaining contraction, but not periodic contraction. Addition of $Ca^{2+}$ to medium evoked periodic contraction which was inhibited by nifedipine, PDBu concentrations of greater than $0.1\;{\mu}M$ increased ^{45}Ca^{2+}$ uptake without changing $^{45}Ca^{2+}$ efflux. Charybdotoxin and apamin, $Ca^{2+}$-activated K^{+}$ channel blockers, did not affect the PDBu-induced periodic contraction, whereas tetraethylammonium (TEA) abolished the periodicity. Pinacidil $(10\;{\mu}M).$, a potassium channel activator, blocked PDBu induced periodic contraction, which was recovered by glybenclamide $(10\;{\mu}M).$. In high potassium solution, PDBu did not produce the periodic contraction. These results suggest that the PDBu-induced periodicity of contraction is modulated by voltage dependent $Ca^{2+}$ channel and ATP-sensitive $K^{+}$ channel.

흰쥐 적출 대동맥에서 alpha1-수용체 효능약과 alpha2-수용체 효능약의 혈관수축반응에 대한 내피세포의 영향

정준기(Joon Ki Chung),홍승철(Sung Cheul Hong),최수경(Su Kyung Choi),강맹희(Maeng Hee Kang),구미경(Mi Geong Ku),박상일(Sang Il Park),윤일(Il Yun) 대한약학회 1990 약학회지 Vol.34 No.3

A comparison was made of the effects of selective alpha1-adrenoceptor agonist phenylephrine and selective alpha2-adrenoceptor agonist clonidine on endothelium-containing and endothelium-denuded rings of the rat aorta. In the case of phenylephrine, removal of endothelium increased sensitivity 2.5 fold at EC50 level and maximum contractive response 1.4 fold. In the case of clonidine, which gave only 15% of maximum contractive response given to phenylephrine on endothelium-containing rings, removal of the endothelium increased sensitivity 5.6 fold at EC50 level and maximum contractive response 5 fold, which was about 55% of that given by phenylephrine. In endothelium-denuded ring, phenylephrine-induced contraction tended to be more increased in tonic contraction than in phasic contraction as compared to that in endothelium-containing ring, while clonidine-induced contraction was monophasic and was increased only in tonic contraction. In the calcium-free solution or in the presence, of verapamil, contraction stimulated by clonidine was almost abolished while that stimulated by phenylephrine produced only phasic contraction. The depression of sensitivity to these agonists in rings with endothelium appeared to be due to the vasodepressor action of endothelium derived relaxing factor(EDRF), because hemoglobin, a specific blocking agent of EDRF, abolished this depression. It is unlikely that the endothelium-dependent relaxation was due to stimulation of release of EDRF, because clonidine did not produce endothelium-dependent relaxation in 5-hydroxytryptamine-precontracted ring even when its contractile action was blocked by the alpha1-adrenoceptor antagonist, prazosin. When the efficacy of phenylephrine was reduced to about the initial efficacy of clonidine by pretreatment with dibenamine, the contraction-response curves for phenylephrine became very similar to the corresponding curves obtained for clonidine before receptor inactivation. In the dibenamine-treated rings, contraction of phenylephrine was abolished in calcium-free solution or in the presence of verapamil like that obtained for clonidine before receptor inactivation. These results suggest that EDRF spontaneously released from endothelium depress contraction more profoundly in a case of an agonist with low efficacy and the phenylephrine-induced contraction was totally dependent on extracellular calcium as was that obtained for clonidine when the efficacy of phenylephrine was reduced to that of clonidine by irreversible inactivation of alpha1-adrenoceptor with dibenamine.

A Diachronic Study of English Negative Contraction

Yookang Kim 한국영어학학회 2007 영어학연구 Vol.- No.23

  Previous studies of negative contraction in English have suggested that several factors play a role in the choice of contracted and uncontracted forms: dialectal variations (Levin 1958, Iyeiri 2001, Wood 2002), syntactic conditions (Blockely 1998, 1990), and standard and non-standard varieties (Brainerd 1989). However, the role of prosody has not been considered as one of the main factors influencing contraction. In addition, all of the previous studies mainly focus on a specific period so they do not provide any overall picture of contraction patterns through all the stages either any diachronic comparison of different contraction patterns. The aim of this paper is to investigate negative contraction patterns from Old English to Modern English, demonstrating the role of prosody in the use of contraction. Under the assumption that contraction of two words is most likely to occur when they are prosodically close to each other, I argue that contraction takes place in a nested prosodic word. The generalization of contracted forms in Modern English is seen as the result of a phonological drift of prosodic structure which is most appropriate for contraction.