• Title/Summary/Keyword: blocker

Search Result 625, Processing Time 0.024 seconds

Effects of GS-386 on the calcium current in rabbit atrial myocytes (GS-386이 단일 심근 세포의 Ca2+ 전류에 미치는 효과)

  • Park, Choon-ok;Chang, Kyeong-jae;Kim, Yang-mi;Haan, Jae-hee;Hong, Seong-geun
    • Korean Journal of Veterinary Research
    • /
    • v.34 no.1
    • /
    • pp.37-47
    • /
    • 1994
  • The effects of the novel compound GS-386 on the calcium current were investigated in rabbit atrial myocytes. The calcium current was recorded during various depolarizations of 200 ms duration from a holding potential of -40 mV using the whole cell patch clamp technique. The calcium current was activated from -30 mV, reached maximum amplitude at +10 mV and almost disappeared at +50 mV. Superfusion of GS-386 led to a reduction of the calcium current amplitude dose-dependently and $ED_{50}$ was $2.5{\times}10^{-7}M$. But the dependence of the calcium current on the membrane potential was not altered by GS-386. The inactivation of the calcium currents showed single exponential curves in both before and after application of GS-386. The inactivation time constants before and after application of GS-386 were almost the same(35 ms and 32.5 ms). The steady-state inactivation curve of the calcium current was not shifted by GS-386. The calcium currents both before and after application of GS-386 recovered completely in 1 sec and the recovery time constants were about 200 ms in both cases. From the above results it is concluded that the novel compound GS-386 has calcium antagonistic property decreasing the calcium current.

  • PDF

Effect of Noradrenaline and Endothelium on the High $K^+$ or Ach-induced Contraction in the Pig Myocardial Coronary Artery (돼지 심근내 관상동맥의 고$K^+$ 및 아세틸콜린 수축에 미치는 노아드레날린과 내피세포의 작용 `)

  • Jang, Dong-Cheol;Lee, Young
    • Journal of Chest Surgery
    • /
    • v.24 no.7
    • /
    • pp.637-646
    • /
    • 1991
  • Effect of noradrenaline and endothelium on the high K+ or Ach-induced contraction were investigated in the pig myocardial coronary artery. The helical strip of isolated pig myocardial coronary artery was immersed in the Tris-buffered Tyrode`s solution equilibrated with 100% O2 at 37oC and its isometric tension was measured. High K+ and Ach-induced contraction were dose-dependent. By denuding the endothelium, dose-contraction curve of K+ was not shifted significantly to the left and upward, but that of Ach was shifted significantly to same direction 25 mM K+ - and Ach-induced contraction were relaxed by norepinephrine[NE]. NE-induced relaxation was blocked by the pretreatment of propranolol, which was known as b-adrenoceptor blocker. And, phenylephrine known as a-adrenoceptor agonist, and clonidine known as a-adrenoceptor agonist increased the 25mM K+ - induced contraction respectively. Denuding of endothelium did not show any significant effects on NE-induced relaxation and contraction increased by phenylephrine and clonidine. Tyramine increased 25mM K+ - induced contraction further. The contractile response by tyramine on the 25mM K+ - induced contraction was not blocked by the pretreatment of phentolamine, but was partially blocked by the pretreatment of atropine. From the above results, it is suggested that activation of a1-and a2-adrenoceptors induce the contraction, activation of b-adrenoceptors induce the relaxation, and NE-induced relaxation is mainly due to activation of b-adrenoceptors. Also it is suggested that denudation of endothelium did not influence NE-induced relaxation, but influence Ach-induced contraction in the pig myocardial coronary artery.

  • PDF

A Study on the Depaminergic Control of T.S.H. Secretion (갑상선자극(甲狀腺刺戟) 호르몬 분비(分泌)에 대(對)한 Dopaminergic Contrl에 관(關)한 연구(硏究))

  • Kim, Myung-Duk;Lee, Jung-Sang;Koh, Chang-Soon;Lee, Mun-Ho;Kim, Eung-Jin
    • The Korean Journal of Nuclear Medicine
    • /
    • v.12 no.2
    • /
    • pp.7-16
    • /
    • 1978
  • To elucidate the depaminergic control of T.S.H. secretion, we analized the pattern of T.S.H. secretion in seven normal controls and nine primary hypothyroid subjects, before and after single or combined administration of specific dopaminergic,receptor blocker, metoclopramide, and specific depaminergic receptor stimulant, bromergocryptine(CB-154). The results obtained were as follows: 1) There was a significant rise in T.S.H. levels after intra venous injection of metocloramide (10mg) in hypothyroid subjects. But there was no significant rise in T.S.H. levels in normal controls. The T.S.H. response to metoclopramide varied considerably, being large in mild cases and small in severely hypothyroid subjects. 2) There was a significant fall in T.S.H. levels after oral administration of bromergocryptine (2mg) in hypothyroid subjects, but there was no significant fall in T.S.H. levels in normal controls. 3) There was no significant fluctuation in T.S.H. levels after combined administration of both metoclopramide and bromergocrytine. 4) There was no significant fluctuation in T.S.H. levels after intravenous injection of normal saline(2ml) in both hypothyroid and normal subjects. 5) There was no significant change in serum $T_3\;and\;T_4$ after administration of metoclopramide and and bromergocryptine respectively and serially. These data support the fact that there is a dopaminergic control in the secretion of T.S.H. in the human.

  • PDF

Induction of Pacemaker Currents by DA-9701, a Prokinetic Agent, in Interstitial Cells of Cajal from Murine Small Intestine

  • Choi, Seok;Choi, Jeong June;Jun, Jae Yeoul;Koh, Jae Woong;Kim, Sang Hun;Kim, Dong Hee;Pyo, Myoung-Yun;Choi, Sangzin;Son, Jin Pub;Lee, Inki;Son, Miwon;Jin, Mirim
    • Molecules and Cells
    • /
    • v.27 no.3
    • /
    • pp.307-312
    • /
    • 2009
  • The interstitial cells of Cajal (ICC) are pacemaking cells required for gastrointestinal motility. The possibility of whether DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, modulates pacemaker activities in the ICC was tested using the whole cell patch clamp technique. DA-9701 produced membrane depolarization and increased tonic inward pacemaker currents in the voltage-clamp mode. The application of flufenamic acid, a non-selective cation channel blocker, but not niflumic acid, abolished the generation of pacemaker currents induced by DA-9701. Pretreatment with a $Ca^{2+}$-free solution and thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum, abolished the generation of pacemaker currents. In addition, the tonic inward currents were inhibited by U-73122, an active phospholipase C inhibitor, but not by $GDP-{\beta}-S$, which permanently binds G-binding proteins. Furthermore, the protein kinase C inhibitors, chelerythrine and calphostin C, did not block the DA-9701-induced pacemaker currents. These results suggest that DA-9701 might affect gastrointestinal motility by the modulation of pacemaker activity in the ICC, and the activation is associated with the non-selective cationic channels via external $Ca^{2+}$ influx, phospholipase C activation, and $Ca^{2+}$ release from internal storage in a G protein-independent and protein kinase C-independent manner.

Effect of Prostaglandins $D_2,\;E_2\;and\;I_2\;on\;the\;Regulation\;of\;K_{ATP}$ Channel Activity in Rat Cardiac Myocytes

  • Ju, Jeong-Min;Nah, Seung-Yeol;Kim, Jae-Ha
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.3 no.5
    • /
    • pp.507-512
    • /
    • 1999
  • Contribution of prostaglandins $D_2,\;E_2\;and\;I_2\;(PGD_2,\;PGE_2\;and\;PGI_2)$ on the regulation of ATP-sensitive $K^+$ channel $(K_{ATP}\;channel)$ was investigated in isolated single rat ventricular cardiac myocytes using the patch clamp technique. $PGD_2,\;PGE_2\;and\; PGI_2$ did not affect $K_{ATP}$ channel activity in the inside-out patch, but increased channel activity in a dose-dependent manner when the channel activities were attenuated by the administration of 100 ${\mu}M$ ATP to the internal solution in the inside-out patch. Channel activations by the prostaglandins were abolished by 50 ${\mu}M$ glibenclamide, a $K_{ATP}$ channel blocker. Dose-response curves of relative channel activity against the ATP concentrations of internal solution in the inside-out patch were shifted to the right in the presence of those three prostaglandins. The rank order of the channel stimulatory potencies $(as\;IC_{50}\;for\;ATP)$ calculated from the dose-response curves were $PGI_2\;>\;PGD_2\;>\;PGE_2.$ Conductance of the channel was not changed by those three prostaglandins. In conclusion, we suggest that prostaglandins $D_2,\;E_2\;and\;I_2$ are involved in the regulation of $K_{ATP}$ channel activity in certain circumstances, and that those three prostaglandins may cause myocardial relaxation by opening $K_{ATP}$ channels, thus protecting the heart from ischema.

  • PDF

The Effect of Intravenous Lipid Emulsion in a Rat Model of Verapamil Toxicity (베라파밀 중독의 쥐 모델에서 지방에멀젼 정맥주사의 효과)

  • Ha, Dae-Myung;Kim, Dong Hoon;Kim, Taeyun;Lee, Soo Hoon;Jeong, Jin Hee;Lee, Sang Bong;Lim, Daesung;Kang, Changwoo
    • Journal of The Korean Society of Clinical Toxicology
    • /
    • v.16 no.1
    • /
    • pp.9-14
    • /
    • 2018
  • Purpose: Intravenous lipid emulsion (ILE) has been shown to have significant therapeutic effects on calcium channel blocker overdose in animal studies and clinical cases. In this preliminary experiment, we investigated the hemodynamic changes and survival in a rat model of verapamil intoxication. Methods: Fourteen male Sprague-Dawley rats were sedated and treated with ILE or normal saline (control), followed by continuous intravenous infusion of verapamil (20 mg/kg/h). Mean arterial pressure and heart rate of rats were monitored during the infusion. In addition, the total dose of infused verapamil and the duration of survival were measured. Results: Survival was prolonged in the ILE group ($32.43{\pm}5.8min$) relative to the control group ($24.14{\pm}4.3min$) (p=0.01). The cumulative mean lethal dose of verapamil was higher in the ILE group ($4.3{\pm}0.7mg/kg$) than in the control group ($3.2{\pm}0.5mg/kg$; p=0.017). Conclusion: ILE pretreatment prolonged survival and increased the lethal dose in a rat model of verapamil poisoning.

Effect of $Ca^{2+}$ and Polyamines on the Activity of $\beta-Glucan$ Synthetase II Related to Cell Wall Synthesis in Carrot Suspension Cultured Cells (당근 현탁배양 세포에서 $Ca^{2+}$과 Polyamines가 Cell Wall 합성에 관여하는 $\beta-Glucan$ Synthetase II 활성에 미치는 영향)

  • 표병식
    • Journal of Plant Biology
    • /
    • v.31 no.2
    • /
    • pp.91-100
    • /
    • 1988
  • The effect of Ca2+ and polyamines on the activity $\beta$-glucan synthetase II(GSII) related to cell wall synthesis was studied in carrot suspension cultured cells. The activity of GS II is four times higher than that of $\beta$-glucan synthetase I in carrot suspension cultured cells and in vitro expreiment, the activity of GSII was increased in response to increase in concentration of Ca2+ and polyamines. When carrot suspension cultured cells were incubated together with Ca2+ and polyamines, the GSII activity was high at 0.1mM of Ca2+ and 1mM of putrescine. Also, polycationic poly-L-lysine and poly-L-ornithine increased about 50% the GSII activity than that of the control, respectively. These results may imply that Ca2+ and polyamines were related to the enzyme activity as a polycationic nature. In addition, verapamil as the calcium channel blocker and flunarizine as an antagonist of calcium mechanism in cytoplasm decreased GSII activity ramarkably, Ca2+ and calmodulin stimulated GSII activity as Ca2+ of free ion rather than Ca2+ calmodulin complex. The effect of 2,4-D on the GSII activity in culture medium is shown to be low at 0.1mg per liter and GSII activity increased about 30% more than that of the 0.1mg/l at the range of 0.3-1.0mg per litere. Cummulative results suggest that Ca2+ and polyfamines stimulate the cell wall synthesis by means of the enhancement of GSII activity responsible for synthesizing the cell wall components.

  • PDF

Dohaekseungkitang extract induced apoptosis in Human Cervical carcinoma HeLa cells (도핵승기탕(桃核承氣湯) 자궁경부암세포(子宮經部癌細胞)(HeLa cell)의 apoptosis에 미치는 영향(影響))

  • Kang, Yong-Goo;Ahn, Kyu-Hwan;Kong, Bok-Cheul;Kim, Song-Baeg;Cho, Han-Baek
    • The Journal of Korean Obstetrics and Gynecology
    • /
    • v.19 no.2
    • /
    • pp.77-91
    • /
    • 2006
  • Purpose : To address the ability of Dohaekseungkitang (DST: a commonly used herb formulation in Korea, Japan and China to have anti-cancer effect on cervical carcinoma), we investigated the effects of DST on programmed cell death (apoptosis) in HeLa human cervical carcinoma cells. Methods : We cultured HeLa cell which is human metrocarcinoma cell in D-MEM included 10% fetal bovine serum(Hyclone Laboratories) below $37^{\circ}C$, 5% CO2. Then we observed apoptosis of log phage cell which is changed cultivation liquid 24 Hours periodically. Results : After the treatment of DST for 48 hours, apoptosis occurred in a dose-dependent manner. In this study, we have shown that DST induces calpain and the associated caspase-8 and -9 activations. Apoptosis was prevented by pre-incubation of the cells with the calcium cHeLator-BAPTA-AM, calcium channel blocker-Nif edipine or Ryonidine agonist-Ryonidine peptide, implicating calcium in the apoptotic process. Ubiquitous calpains (mu- and m-calpain) have been repeatedly implicated in apoptosis, especially in calcium-related apoptosis. However this study showed 1hat either calpain inhibitor-calpastin or caspase-3 inhibitor-DEVD- did not blocked the herb formulation-induced apoptosis in HeLa human cervical carcinoma cells. D ST initiates a cell death pathway that is partially dependent of caspases. DST-induced apoptosis requires caspase-independent mechanism. Conclusion : We conclude that DST-induced calpain activation triggers the intrinsic apoptotic pathway in which caspase-independent mechanism is also involved.

  • PDF

Effects of Sunghyangchungisan on contractile Reactivity of Isolated Rabbit Carotid Artery (성향정기산(星香正氣散)이 가토(家?)의 경동맥(頸動脈) 평활근(平滑筋) 긴장도(緊張度) 조절(調節)에 미치는 영향(影響))

  • Kim, Young-Kyun;Ko, Woo-Shin;Kim, Jong-Hoon
    • The Journal of Korean Medicine
    • /
    • v.19 no.2
    • /
    • pp.228-243
    • /
    • 1998
  • This study was undertaken to evaluate the effect of Sunghyangchungisan (SHCS) on the regulation of vascular tone. Vascular rings isolated from rabbit carotid artery were myographed isometrically in isolated organ baths and the effect of SHCS on contractile activities were determined. SHCS relaxed the arterial rings which were pre-contracted by phenylephrine(PE). The responses to SHCS were partially dose-dependent at concentrations lower than 0.5 mg/ml. When SHCS was applied prior to the exposure to PE, it inhibited the PE-induced contraction by a similar magnitude which was comparable to the relaxation of pre-contracted arterial rings. Washout of SHCS after observing its relaxant effect resulted in a full recovery of PE-induced contractions, indicating that the action mechanism is reversible. The observation that SHCS did not change the $ED_{50}$ of PE on its dose-response curve ruled out the possible interaction of SHCS and ${\alpha}-receptor$. The relaxant effect of SHCS was not affected by removal of endothelium, and pretreatment of the arterial rings with methylene blue or nitro-L-arginine. This results suggest that the action of SHCS is not mediated by endothelium nor soluble guanylate cyclase. SHCS relaxed high $K^{+}-induced$ contractions as well, whereas it failed to relax phorbol ester-induced contractions. When contraction was induced by additive application of $Ca^{2+}$ in arterial rings which were pre-depolarized by high $K^+$ in a $Ca^{2+}-free$ solution, the relaxant effect of SHCS was attenuated by increasing the $Ca^{2+}$ concentration. SHCS, when applied to the arterial rings pre-contracted by PE and then relaxed by nifedipine, a $Ca^{2+}$ channel blocker, did not show additive relaxation. From above results, it is suggested that SHCS relax PE-induced contraction of rabbit carotid artery in an endothelium-independent manner, and inhibition of $Ca^{2+}$ influx may contribute to the underling mechanism.

  • PDF

Types of Parental Gatekeeping in Drama 「SKY Castle」 (드라마 「SKY 캐슬」에 나타난 아버지와 어머니의 문지기 유형)

  • Yee, Young-Hwan
    • The Journal of the Korea Contents Association
    • /
    • v.20 no.1
    • /
    • pp.593-604
    • /
    • 2020
  • The purpose of this study is to analyze parental gatekeeping dimensions(control, encouragement, discouragement) and types of gatekeeping in the two families featured in the drama 「SKY Castle」. Of the 8 types of gatekeeping, the traditional gate blocker(high control, low encouragement, and high discouragement) most often described in the drama, creates a difficult situation for a father trying to participate in child rearing. But traditional gate blockers do not always unnecessarily limit father involvement. In father's coerecive and dictatorial environment, traditional maternal gatekeeping strategies protect her children and create secure environment. The facilitative gate openers(high control, high encouragement, and low discouragement) is the functional gatekeeping type. Because the mother's highly controlling and highly encouraging ways serve as a positive coparenting strategy, the facilitative gate maintain a high level of authority over the amount and type of father involvement.