• 약학회지
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• 제58권1호
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• pp.16-20
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• 2014

KR-31064 was developed for the strong angiotensin II receptor antagonist among the one of pyridyl imidazol series compounds. To investigate the receptor-ligand binding characteristics of this nonpeptide antagonist, binding experiments were deployed in various conditions and ex vivo contractile responses were tested toward the standard compound, losartan. Receptor binding experiments with radiolabeled angiotensin II, the $IC_{50}$ value for KR-31064 resulted 0.67 nM without any activities toward type 2 angiotensin II receptor. The comparative potency against losartan was more than 18 fold and the specific activity in type 1 angiotensin II receptor was more than 10,000 fold comparing to the type 2 receptor. Scatchard analysis of saturation binding data showed KR-31064 acted on the receptor in a competitive mode. KR-31064 inhibited the contractile response derived by angiotensin II ($pK_B$: 9.86) similar to that of losartan with decreased maximum signals. As a potent and specific type 1 angiotensin II receptor antagonist, KR-31064 may have possibilities for the development of diagnostic ligands that can be used as tools for various biochemical research experiments and non-invasive diagnostics.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.192-202
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• 2003

The wrinkles correspond to the most obvious expression of skin ageing and are manifested by changes on the organization and dermal structure. In the extracellular matrix, decreased quantities of collagens and glycosaminoglycans as well as a deterioration of the fibrillary network is noted, result in a reduction of dermal thickness. In addition, the activity of the collagenases increases in contrast to the synthesis of collagen fibers. Nor are cells spared during the aging process. We thus studied and compared the contractile capacity as well as the synthesis capacity of normal human fibroblasts and human fibroblasts obtained from biopsies of forehead wrinkles. The capacity of the fibroblasts to be adhered to the collagen network and to maintain a three-dimensional structure of dermis was studied on a model of equivalent dermis. The metabolic activity was studied by evaluating the capacities of synthesis of collagen I, main component of dermis. Human fibroblasts resulting from the forehead wrinkle contract less the gel of collagen than the normal human fibroblasts and present an activity of biosynthesis of collagen I less important than normal human fibroblasts. These results show that fibroblasts with aging present a deceleration of their metabolic activity and lose their capacity of adhesion to collagen fibers thus limiting the possibility of organizing the dermal tissue. We investigated the potential of an active ingredient able to compensate for the reduction of the metabolic activity and to restore the contractile capacity of fibroblasts obtained from forehead wrinkles. This effect was compared with a reference molecule: the vitamin C.

• The Korean Journal of Physiology and Pharmacology
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• 제21권4호
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• pp.385-395
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• 2017

Vasoconstrictive properties of sympathomimetic drugs are the basis of their widespread use as decongestants and possible source of adverse responses. Insufficiently substantiated practice of combining decongestants in some marketed preparations, such are those containing phenylephrine and lerimazoline, may affect the overall contractile activity, and thus their therapeutic utility. This study aimed to examine the interaction between lerimazoline and phenylephrine in isolated rat aortic rings, and also to assess the substrate of the obtained lerimazoline-induced attenuation of phenylephrine contraction. Namely, while lower concentrations of lerimazoline ($10^{-6}M$ and especially $10^{-7}M$) expectedly tended to potentiate the phenylephrine-induced contractions, lerimazoline in higher concentrations ($10^{-4}M$ and above) unexpectedly and profoundly depleted the phenylephrine concentration-response curve. Suppression of NO with NO synthase (NOS) inhibitor $N^w$-nitro-L-arginine methyl ester (L-NAME; $10^{-4}M$) or NO scavanger $OHB_{12}$ ($10^{-3}M$), as well as non-specific inhibition of $K^+$-channels with tetraethylammonium (TEA; $10^{-3}M$), have reversed lerimazoline-induced relaxation of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin ($10^{-5}M$) did not affect the interaction between two vasoconstrictors. At the receptor level, non-selective 5-HT receptor antagonist methiothepin reversed the attenuating effect of lerimazoline on phenylephrine contraction when applied at $3{\times}10^{-7}$ and $10^{-6}M$, but not at the highest concentration ($10^{-4}M$). Neither the 5-$HT_{1D}$-receptor selective antagonist BRL 15572 ($10^{-6}M$) nor 5-$HT_7$ receptor selective antagonist SB 269970 ($10^{-6}M$) affected the lerimazoline-induced attenuation of phenylephrine activity. The mechanism of lerimazoline-induced suppression of phenylephrine contractions may involve potentiation of activity of NO and $K^+$-channels and activation of some methiothepin-sensitive receptors, possibly of the 5-$HT_{2B}$ subtype.

• 한국가축번식학회지
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• 제18권2호
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• pp.101-104
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• 1994

임신기간중 oxytocin의 역할을 규명하기 위해 그리고 조기분만 진통의 억제제로서 수많은 강력한 oxytocin antagonist들이 개발되고 있다. 본 연구는 발정된 흰쥐를 사용하여 oxytocin antagonist I(AI)이 control과 비교하여 자궁에 어떠한 활동을 보이는지를 알아보는 것이 주 목적이었다. AI과 control로서 saline을 주입하기 위해 경정맥에 cannula를 수술하여 집어 넣었고, 또 다른 cannula는 자궁활동을 측정하기 위해 자궁각에 집어 넣었다. 자궁수축상호아은 Grass Polygraph를 사용하여 측정하였고 수축활동은 10분동안의 integrated area를 계산하여 측정되었다. 5$\mu\textrm{g}$의 AI을 주입한 5분후 100mU의 oxytocin이 주입되었고 이 oxytocin주입은 매시간 5시간 동안 계속되었다. AI이 주입된 5분 후, oxytocin에 대한 자궁의 수축반응은 control에 비해 77% 감소되었다(P<0.05). AI 주입 2시간 후에는 그 감소가 control에 비해 54%였다. 그러나 3시간 이후부터 AI은 control과 어떤 유의한 차이를 보이지 않았다. AI이 인간의 조기분만진통을 방지하는데 사용될 수 있다는 잠재 가능성을 본 연구에서 확인하였다.

• 대한약리학회지
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• 제30권1호
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• pp.59-65
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• 1994

기아(starvation)기간중 흰쥐의 심근세포내에 심장의 수축 기능에 필요한 내인성 대사 기질인 지질의 축적이 증가된다는 사실이 알려져 있다. 본 연구에서는 lidocaine의 심근내 지방대사에 대한 영향을 기능적 측면에서 관찰하기 위하여, 굶긴 쥐 적출 심장의 수축성에 대한 lidocaine의 영향을 검토한바 다음과 같은 실험결과를 얻었다. 1. 굶긴 쥐 체중은 정상쥐에 비하여 현저히 감소되었으며, 기아시작 4일에서 약 30%의 체중감소를 나타했다. 그러나 정상쥐의 체중은 증가되었다. 2. 정상 쥐의 적출 심방은 기질제거 용액에서 30분에 약 40%의 현저한 수축력의 감소를 보였다. 그러나 2일간 굶긴 쥐의 적출 심장은 기질제거용액에서 30분에 약 13%의 수축력의 감소를 보여 정상 쥐에서의 수축력 저하보다 현저히 낮은 감소율을 나타냈다. 3. Lidocaine(0.1mM)에 의한 흰쥐 적출 심장의 수축력 감소는 정상쥐에 비해 굶긴 쥐 적출 심장의 수축력이 작게 감소되었다. 또한, lidocaine에 의한 굶긴 쥐 적출심장의 감소율은, 1일간 굴긴 쥐 보다 2일간 굴긴 쥐의 적출심장이 현저히 더 작게 감소되었다. 이상의 결과로 미루어 보아, 굶기는 동안 쥐 심근 내에 축적된 내인성 대사 기질인 지질이 lidocaine에 의해 해당과정이 억제된 심장의 수축과정에 energy원으로 쓰여지고 있을 가능성을 시사하고 있다.

• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.227-234
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• 2000

Many reports suggest that neurotensin (NT) in the gastrointestinal tract may play a possible role as a neurotransmitter, a circulating hormone, or a modulator of motor activity. NT exerts various actions in the intestine; it produces contractile and relaxant responses in intestinal smooth muscle. This study was designed to investigate the effect of NT on motility of antral circular muscle strips in guinea-pig stomach. To assess the role of $Ca^{2+}$ influx in underlying mechanism, slow waves were simultaneously recorded with spontaneous contractions using conventional intracellular microelectrode technique. At the concentration of $10^{-7}$ M, where NT showed maximum response, NT enhanced the magnitude $(863{\pm}198%,\;mean\;SEM,\;n=13)$ and the frequency $(154{\pm}10.3%,\;n=11)$ of spontaneous contractions. NT evoked a slight hyperpolarization of membrane potential, tall and steep slow waves with abortive spikes $(278{\pm}50%,\;n=4).$ These effects were not affected by atropine $(2\;{\mu}M),$ guanethidine $(2\;{\mu}M)$ and tetrodotoxin (0.2μM). NT-induced contractile responses were abolished in $Ca^{2+}-free$ solution and reduced greatly to near abolition by $10\;{\mu}M$ of verapamil or 0.2 mM of $CdCl_2.$ Verapamil attenuated the effects of NT on frequency and amplitude of the slow waves. Taken together, these results indicate that NT enhances contractility in guinea-pig gastric antral circular muscle and $Ca^{2+}$ influx through the voltage-operated $Ca^{2+}$ channel appears to play an important role in the NT-induced contractile mechanism.

• International Neurourology Journal
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• 제22권4호
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• pp.246-251
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• 2018

Purpose: To determine whether responses to serotonin are altered in bladder strips from cats diagnosed with a naturally occurring form of bladder pain syndrome/interstitial cystitis termed feline interstitial cystitis (FIC). Methods: Full thickness bladder strips were isolated from aged matched healthy control cats and cats with clinically verified FIC. Bladder strips were mounted in an organ bath and connected to a tension transducer to record contractile activity. A serotonin dose response ($0.01-10{\mu}M$) was determined for each strip with the mucosa intact or denuded. Results: Bladder strips from control and FIC cats contracted in response to serotonin in a dose-dependent manner. The normalized force of serotonin-evoked contractions was significantly greater in bladder strips from cats with FIC (n=7) than from control cats (n=4). Removal of the mucosa significantly decreased serotonin-mediated responses in both control and FIC bladder preparations. Furthermore, the contractions in response to serotonin were abolished by $1{\mu}M$ atropine in both control and FIC bladder strips. Conclusions: The effect of serotonin on contractile force, but not sensitivity, was potentiated in bladder strips from cats with FIC, and was dependent upon the presence of the mucosa in control and FIC groups. As atropine inhibited these effects of serotonin, we hypothesize that, serotonin enhances acetylcholine release from the mucosa of FIC cat bladder strips, which could account for the increased force generated. In summary, FIC augments the responsiveness of bladder to serotonin, which may contribute to the symptoms associated with this chronic condition.

• 한국운동역학회지
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• 제32권3호
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• pp.103-110
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• 2022

Objective: The aim of this study was to investigate effect of core stabilization exercises on the erector spinae contractile properties and trunk isokinetic muscle function of middle age with low physical activity and sedentary lifestyle. Method: Twenty (female: n=10, male: n=10) middle-age subjects (age: 37.25 ± 6.08 years, height: 168.01 ± 6.84 cm, weight: 71.37 ± 11.75 kg) participated in this study. Tensiomyography was measured on the erector spinae, and the isokinetic trunk muscle function test was measured at an angular velocity of 60 °/s and 90 °/s. All subjects performed the core stabilization exercises for 60 min per day, 3 times a week, for 7 weeks. A paired t-test was performed with a significance level of 0.05. Results: Tensiomyography of the erector spinae revealed a significant post-exercise increase in the maximum radial displacement (p < .05) and velocity of contraction (p < .05), however, there wasn't a significant post-exercise change in the contraction time. Additionally, the isokinetic muscle function test of the trunk revealed a significant post-exercise increase in trunk extensor relative strength (p < .05) and strength ratio (p < .05). Conclusion: Our results indicated that core stabilization exercises reduced erector spinae muscle stiffness, increased the velocity of erector spinae contraction. Additionally, data showed the improvement in the trunk extensor strength help induce a more balanced development in trunk muscle.

• Journal of Nutrition and Health
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• 제30권6호
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• pp.634-648
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• 1997

To examine the effect of Artemisia princeps var orientalis on cardiovascular system, cadiovascular response from its water extracts were studied in the atria and aortae of normal rats. The extracts diminished spontaneous beat and contractile force in the left and right atria, and caused the relaxation of thoraic aortae. As for the blood pressure, the mugwort extract had a descending effect.

• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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• pp.37-44
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• 2017

Regulation of vascular smooth muscle cell (VSMC) phenotype plays an essential role in many cardiovascular diseases. In the present study, we provide evidence that $kr{\ddot{u}}ppel$-like factor 8 (KLF8) is essential for tumor necrosis factor ${\alpha}$ ($TNF{\alpha}$)-induced phenotypic conversion of VSMC obtained from thoracic aorta from 4-week-old SD rats. Stimulation of the contractile phenotype of VSMCs with $TNF{\alpha}$ significantly reduced the VSMC marker gene expression and KLF8. The gene expression of KLF8 was blocked by $TNF{\alpha}$ stimulation in an ERK-dependent manner. The promoter region of KLF8 contained putative Sp1, KLF4, and $NF{\kappa}B$ binding sites. Myocardin significantly enhanced the promoter activity of KLF4 and KLF8. The ectopic expression of KLF4 strongly enhanced the promoter activity of KLF8. Moreover, silencing of Akt1 significantly attenuated the promoter activity of KLF8; conversely, the overexpression of Akt1 significantly enhanced the promoter activity of KLF8. The promoter activity of SMA, $SM22{\alpha}$, and KLF8 was significantly elevated in the contractile phenotype of VSMCs. The ectopic expression of KLF8 markedly enhanced the expression of SMA and $SM22{\alpha}$ concomitant with morphological changes. The overexpression of KLF8 stimulated the promoter activity of SMA. Stimulation of VSMCs with $TNF{\alpha}$ enhanced the expression of KLF5, and the promoter activity of KLF5 was markedly suppressed by KLF8 ectopic expression. Finally, the overexpression of KLF5 suppressed the promoter activity of SMA and $SM22{\alpha}$, thereby reduced the contractility in response to the stimulation of angiotensin II. These results suggest that cross-regulation of KLF family of transcription factors plays an essential role in the VSMC phenotype.