• 대한한방내과학회지
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• 제26권1호
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• pp.221-228
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• 2005

The intent of this study is to investigate whether two oriental medical prescriptions named haengsotang(HST) and gami-palmihwan(GPMH) significantly effect mucin release from cultured hamster tracheal surface epithelial(HTSE) cells, Confluent HTSE cells were metabolically radiolabeled with $^3H-glucosamine$ for 24 hrs and chased for 30 min in the presence of HST or GPMH to assess the effect of each agent on $^3H-mucin$ release. Possible cytotoxicities of each agent were assessed by measuring lactate dehydrogenase(LDH) release. Also, the effects of HST and GPMH on contractility of isolated tracheal smooth muscle were investigated. The results are consistant with the following assertions: (1) HST significantly inhibited mucin release from cultured HTSE cells, without cytotoxicity; (2) GPMH did not effect mucin release without cytotoxicity; (3) HST and GPMH did not effect contractility of isolated tracheal smooth muscle. These results suggest a need for further investigation of HST and its components, for its potential in oriental medicine prescriptions and novel agents that effectively regulate (inhibit) mucin secretion from airway goblet cells.

• 대한한방소아과학회지
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• 제21권1호
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• pp.139-154
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• 2007

Objectives : The author intended to investigate Seonbangpaedoktang (SBPT) significantly affect in vivo and in vitro mucin secretion from airway epithelial cells. Methods : In vivo experiment, the author induced hypersecretion of airway mucin, hyperplasia of tracheal goblet cells and the increase in intraepithelial mucosubstances. Effects of orally-administered SBPT during 1 week on in vivo mucin secretion and hyperplasia of tracheal goblet cells were assessed. For in vitro experiment, confluent hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled and chased in the presence of SBPT to assess the effect of the agent on 3H-mucin secretion. Total elution profiles of control spent media and treatment sample through Sepharose CL-4B column were analysed. Possible cytotoxicity of the agent was assessed by measuring LDH release. Also, the effect of SBPT on contractility of isolated tracheal smooth muscle was investigated. Results : SBPT inhibited hypersecretion of in vivo mucin and inhibited the increase of number of goblet cells ; SBPT did not affect in vitro mucin secretion and the secretion of the other releasable glycoproteins with less molecular weight than mucin from cultured HTSE cells, without significant effect on LDH release; SBPT did not affect Ach-induced contraction of isolated tracheal smooth muscle. Conclusions : SBPT can inihibit hypersecretion of in vivo mucin and the author suggest that the effect SBPT with their components should investigate further.

• 대한약리학회지
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• 제11권2호
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• pp.19-27
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• 1975

Haloperidol, a butyrophenone, was synthetized by Janssen and introduced for the treatment of psychosis. Although structurally different from the phenothiazines, the butyrophenones share many of their pharmacological properties, such as inhibition of conditioned avoidance response, blocking effect of amphetamine reaction, producing catalepsy, antishock effect and protection against the lethal effects of catecholalmines. Chlorpromazine can lower the arterial blood pressure through its adrenergic blocking activity, its direct effect in relaxing vascular smooth muscle, its direct effect in depressing the myocardium and its action in a complex manner on the central nervous system. In the case of haloperidol, however, was not clarified the mechanism of lowering the blood pressure. The present paper describes the effects of haloperidol on cardiovascular system to investigate the mechanisms of its actions on the arterial blood pressure. The results are followings; 1. In anesthetized cats, intravenous administration of haloperidol and chlorpromazine in the dose of 0.1mg/kg produced a slight decrease in the blood pressure, which followed by complete recovery within $30{\sim}60$ minutes. In the dose of 3mg/kg, however, both produced an abrupt and marked decrease of the blood pressure, which followed by delayed recovery. 2. Haloperidol in the dose ranges of 0.1mg to 3.0mg/kg tended to produce the heart rate slowing in the cats, while chlorpromazine has no effect on the rate. 3. Following administration of haloperidol or chlorpromazine, epinephrine reversal in the arterial blood pressure was observed in the cat, however the responses of norepinephrine and acetylcholine were little affected. 4. In the isolated rabbit atrium the contractility was depressed by haloperidol in the doses over 0.5mg per 100ml, but the rate was not affected. In contrast, the epinephrine-induced contractility was not depressed after haloperidol treatment. However, the increased rate of atrium by epinephrine was partially blocked after haloperidol. 5. In the isolated rabbit aortic strip, epinephrine-induced contraction was blocked by haloperidol. With the above results, it may be concluded that the hypotensive effect of haloperidol was largely due to ${\alpha}$-adrenergic blocking properties and the direct effect in depressing the myocardium as well as its action on central nervous system.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.361-368
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• 1998

The spontaneous contractions of gastric smooth muscles are regulated by slow waves, which are modulated by both nervous system and humoral agents. This study was designed to examine the effects of prostaglandin $E_2$ ($PGE_2$) on the contractile and electrical activities of antral smooth muscles in guinea-pig stomach, using an intracellular recording technique. To elucidate the underlying mechanism for its effect on contractility, ionic currents were also measured using a whole-cell patch clamp method. The basal tone by $PGE_2$ was variable, whereas the magnitude of phasic contractions was reduced ($19.0{\pm}2.1%$, n=19). The resting membrane potentials were hyperpolarized ($-4.4{\pm}0.5%$ mV, n=10), and plateau potentials were lowered ($-2.9{\pm}0.5%$ mV, n=10). In most cases, however, the initial peak potentials of slow waves were depolarized more by $PGE_2$ than those of control. The frequency of the slows wave was increased from $5.7{\pm}0.2$ cycles/min to $6.5{\pm}0.2$ (n=22). Voltage-operated $Ca^{2+}$ currents were decreased by $PGE_2$ (n=5). Voltage-operated $K^+$ currents, both Ca-dependent and Ca-independent, were increased (n=5). These results suggest that $PGE_2$ plays an important role in the modulation of gastric smooth muscle activities, and its inhibitory effects on the contractility and activities of slow waves are resulted from both decrease of $Ca^{2+}$ currents and increase of $K^+$ currents.

• The Korean Journal of Physiology and Pharmacology
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• 제16권6호
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• pp.437-446
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• 2012

Ulcerative colitis is an inflammatory bowel disease (IBD) characterized by recurrent episodes of colonic inflammation and tissue degeneration in human or animal models. The contractile force generated by the smooth muscle is significantly attenuated, resulting in altered motility leading to diarrhea or constipation in IBD. The aim of this study is to clarify the altered contractility of circular and longitudinal smooth muscle layers in proximal colon of trinitrobenzen sulfonic acid (TNBS)-induced colitis mouse. Colitis was induced by direct injection of TNBS (120 mg/kg, 50% ethanol) in proximal colon of ICR mouse using a 30 G needle anesthetized with ketamin (50 mg/kg), whereas animals in the control group were injected of 50% ethanol alone. In TNBS-induced colitis, the wall of the proximal colon is diffusely thickened with loss of haustration, and showed mucosal and mucular edema with inflammatory infiltration. The colonic inflammation is significantly induced the reduction of colonic contractile activity including spontaneous contractile activity, depolarization-induced contractility, and muscarinic acetylcholine receptor-mediated contractile response in circular muscle layer compared to the longitudinal muscle layer. The inward rectification of currents, especially, important to $Ca^{2+}$ and $Na^+$ influx-induced depolarization and contraction, was markedly reduced in the TNBS-induced colitis compared to the control. The muscarinic acetylcholine-mediated contractile responses were significantly attenuated in the circular and longitudinal smooth muscle strips induced by the reduction of membrane expression of canonical transient receptor potential (TRPC) channel isoforms from the proximal colon of the TNBS-induced colitis mouse than the control.

• Biomolecules & Therapeutics
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• 제20권4호
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• pp.386-392
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• 2012

The endothelin (ET) signaling pathway controls many physiological processes in myocardium and often becomes upregulated in heart diseases. The aim of the present study was to investigate the effects of ET receptor upregulation on the contractile function of adult ventricular myocytes. Primary cultured adult rat ventricular myocytes were used as a model system of ET receptor overexpression in the heart. Endothelin receptor type A ($ET_A$) or type B ($ET_B$) was overexpressed by Adenoviral infection, and the twitch responses of infected ventricular myocytes were measured after ET-1 stimulation. Overexpression of $ET_A$ exaggerated positive inotropic effect (PIE) and diastolic shortening of ET-1, and induced a new twitch response including twitch broadening. On the contrary, overexpression of $ET_B$ increased PIE of ET-1, but did not affect other two twitch responses. Control myocytes expressing endogenous receptors showed a parallel increase in twitch amplitude and systolic $Ca^{2+}$ in response to ET-1. However, intracellular $Ca^{2+}$ did not change in proportion to the changes in contractility in myocytes overexpressing $ET_A$. Overexpression of $ET_A$ enhanced both systolic and diastolic contractility without parallel changes in $Ca^{2+}$. Differential regulation of this nature indicates that upregulation of $ET_A$ may contribute to diastolic myocardial dysfunction by selectively targeting myofilament proteins that regulate resting cell length, twitch duration and responsiveness to prevailing $Ca^{2+}$.

• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.403-409
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• 2019

Free fatty acid (FFA) intake regulates blood pressure and vascular reactivity but its direct effect on contractility of systemic arteries is not well understood. We investigated the effects of saturated fatty acid (SFA, palmitic acid), polyunsaturated fatty acid (PUFA, linoleic acid), and monounsaturated fatty acid (MUFA, oleic acid) on the contractility of isolated mesenteric (MA) and deep femoral arteries (DFA) of Sprague-Dawley rats. Isolated MA and DFA were mounted on a dual wire myograph and phenylephrine (PhE, $1-10{\mu}M$) concentration-dependent contraction was obtained with or without FFAs. Incubation with $100{\mu}M$ of palmitic acid significantly increased PhE-induced contraction in both arteries. In MA, treatment with $100{\mu}M$ of linoleic acid decreased $1{\mu}M$ PhE-induced contraction while increasing the response to higher PhE concentrations. In DFA, linoleic acid slightly decreased PhE-induced contraction while $200{\mu}M$ oleic acid significantly decreased it. In MA, oleic acid reduced contraction at low PhE concentration (1 and $2{\mu}M$) while increasing it at $10{\mu}M$ PhE. Perplexingly, depolarization by 40 mM KCl-induced contraction of MA was commonly enhanced by the three fatty acids. The 40 mM KCl-contraction of DFA was also augmented by linoleic and oleic acids while not affected by palmitic acid. SFA persistently increased alpha-adrenergic contraction of systemic arteries whereas PUFA and MUFA attenuated PhE-induced contraction of skeletal arteries. PUFA and MUFA concentration-dependent dual effects on MA suggest differential mechanisms depending on the types of arteries. Further studies are needed to elucidate underlying mechanisms of the various effects of FFA on systemic arteries.

• 대한약침학회지
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• 제25권3호
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• pp.209-215
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• 2022

Objectives: Aqueous leaf extract of Tridax procumbens (ALETP) has potent relaxant activity. However, this relaxant activity in respiratory smooth muscle remains uninvestigated. This study investigates the effect of ALETP on the contractile activity of tracheal smooth muscle (TSM) in adult male Wistar rats. Methods: Twelve male Wistar rats divided into 2 groups and were treated with either 100 mg/kg of ALETP (ALETP treatment group) or vehicle (distilled water; control group) through oral gavage for 4 weeks. Dose responses of TSM from the 2 groups to acetylcholine (10^-9 to 10^-5 M), phenylephrine (10^-9 to 10^-5 M), and potassium chloride (KCl; 10^-9 to 10^-4 M) were determined cumulatively. Furthermore, cumulative dose responses to acetylcholine (10^-9 to 10^-5 M) after pre-incubation of TSM with atropine (10^-5 M), L-NAME (10^-4 M), indomethacin (10^-4 M), and nifedipine (10^-4 M), were determined. Results: Treatment with ALETP substantially inhibited TSM contraction stimulated by cumulative doses of acetylcholine, phenylephrine, and KCl. Furthermore, preincubation of TSM from the 2 groups in atropine significantly inhibited contractility in TSM. Incubation in L-NAME and indomethacin also significantly inhibited contractility in TSM of ALETP-treated rats compared to that of controls. Contractile activity of the TSM was also inhibited significantly with incubation in nifedipine in ALETP-treated rats. Conclusion: ALETP enhanced relaxant activity in rat TSM primarily by blocking the L-type calcium channel and promoting endothelial nitric oxide release. ALETP contains agents that may be useful in disorders of the respiratory tract.

• Clinical and Experimental Pediatrics
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• 제45권2호
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• pp.214-222
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• 2002

목 적 : Anthracylines계 약물은 매우 효과적이며 널리 사용되고 있는 항암제이다. 그러나 심근손상이라는 중요한 합병증이 있으며 이는 종종 중하거나 심지어는 치명적이다. 본 연구의 목적은 anthracyacline을 사용했던 소아 암환자에서 비침습적이고 비교적 안전한 심장초음파를 이용하여, 기존의 지표에 비해 좀 더 정확하고 주위변수의 영향을 덜 받으면서 심근손상 여부를 판정하기 위해 고안되었다. 방 법 : Adriamycin을 투여 받았던 17명의 환자군과 20명의 대조군을 대상으로 좌심실 내경, 심실벽 긴장도 그리고 수축기능이 평가되었다. 17명의 환자에 대해서는 2번에 걸쳐 검사가 시행되었는데, 휴식상태(group 1)와 운동을 하고 난후(group 2)에 검사를 각각 시행하였다. 결 과 : 이완기 말 좌심실 내경은 두 군에서 모두 정상 대조군에 비해 감소된 소견을 보였고 통계적으로 의미가 있었다. 그러나 두 군간의 통계적인 차이는 없었다. 이완기 말 좌심실 용적과 심실벽 크기는 두군에서 정상 대조군에 비해 감소된 소견을 보였으며, 통계적으로 모두 의미가 있었다. Group 2에서 group 1보다 낮은 값을 보였으나, 두 군간의 통계적인 의미는 없었다. 수축기말 경선 긴장도는 두 군에서 모두 증가하였으며, group 1에서 group 2 보다 낮은 값을 보였으나, 두 군간의 통계적인 의미는 없었다. 분획단축으로 평가된 수축능력은 group 1에서는 17명 중 5명(29%)에서 비정상적인 결과를 나타내었고, group 2에서는 17명 중 6명(35%)에서 수축능력의 이상을 나타내었다. 그러나 nonparametric testing으로 검정한 결과 두 군간의 특이한 차이는 없었다. 한편, 부하 비의존적 지표인 원주상 섬유 단축속도와 수축기말 경선 긴장도와의 관계에 있어서는 두 군간에 차이가 있음이 관찰되었는데, group 1에서 17명 중 7명(41%), group 2에서는 17명 중 12명(71%)에서 현저한 비정상 변화를 보였으며, 이는 통계적으로 의미가 있었다. 결 론 : 분획단축과 같은 부하 의존적 수축기 지표는 전부하 혹은 후부하의 보상적 변화에 의해서 비정상소견을 보이지 않을 수 있으며, 이로 인해 수축력의 장애가 가려질 수 있다. 따라서 부하 비의존적 지표인 수축기 말 압력과 내경과의 기울기 관계 및 운동 후 수축기말 심실벽 긴장에 따른 원주상 섬유 단축속도의 변화를 규명함으로써 심장의 수축능력을 지속적으로 감시하는 것이 심근손상의 조기발견에 도움이 될 것으로 생각된다.

• Journal of Chest Surgery
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• 제23권3호
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• pp.452-464
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• 1990

It is well known that extracellular Calcium plays a very important role in several steps of smooth muscle excitability and contractility, and there have been many concerns about factors influencing the distribution of extracellular Ca++ and the Ca++ flux through the cell membrane of the smooth muscle. Based on the assumption that Mg++ may also play an important role in the excitation and contraction processes of the smooth muscle by taking part in affecting Ca++ distribution and flux, many researches are being performed about the exact role of Mg++, especially in the vascular smooth muscle. But yet the effect of Mg++ in the smooth muscle activity is not clarified, and moreover the mechanism of Mg++ action is almost completely unknown. Present study attempted to clarify the effect of Mg++ on the excitability and contractility in the multiunit and unitary smooth muscle, and the mechanism concerned in it. The preparations used were the guinea-pig aortic strip as the experimental material of the multiunit smooth muscle and the rat uterine strip as the one of the unitary smooth muscle. The tissues were isolated from the sacrificed animal and were prepared for recording the isometric contraction. The effects of Mg++ and Ca++ were examined on the electrically driven or spontaneous contraction of the preparations. And the effects of these ions were also studied on the K+ or norepinephrine contracture. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% 02 and kept at 35oC. The results obtained were as follows: 1] Mg++ suppressed the phasic contraction induced by electrical field stimulation dose-dependently in the guinea-pig aortic strip, while the high concentration of Ca++ never recovered the decreased tension. These phenomena were not changed by the a - or b - adrenergic blocker. 2]Mg++ played the suppressing effect on the low concentration [20 and 40 mM] of K+-contracture in the aortic muscle, but the effect was not shown in the case of 100mM K+-contracture. 3] Mg++ also suppressed the contracture induced by norepinephrine in the aortic preparation. And the effect of Mg++ was most prominent in the contracture by the lowest [10 mM] concentration of norepinephrine. 4] In both the spontaneous and electrically driven contractions of the uterine strip, Mg++ decreased the amplitude of peak tension, and by the high concentration of Ca++ the amplitude of tension was recovered unlike the aortic muscle. 5] The frequency of the uterine spontaneous contraction increased as the [Ca++] / [Mg++] ratio increased up to 2, but the frequency decreased above this level. 6] Mg++ decreased the tension of the low[20 and 40mM] K+-contracture in the uterine smooth muscle, but the effect did not appear in the 100mM K+-contracture. From the above results, the following conclusion could be made. 1] Mg++ seems to suppress the contractility directly by acting on the smooth muscle itself, besides through the indirect action on the nerve terminal, in both the aortic and uterine smooth muscles. 2] The fact that the depressant effect of Mg++ on the K+-contracture is in inverse proportion to an increase of K+ concentration appears resulted from the extent of the opening state of the Ca++ channel. 3] Mg++ may play a depressant role on both the potential dependent and the receptor-operated Ca++ channels. 4] The relationship between the actions of Mg++ and Ca++ seems to be competitive in uterine muscle and non-competitive in aortic strip.