• 대한치과의사협회지
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• 제16권7호통권110호
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• pp.531-536
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• 1978

Adult cats were light anesthetized with ethyl ether and heart was removed fastly. cardiac papillary muscle was dissected from heart in organ bath con taining Tyrode solution saturated with 95% O₂+5% CO₂, and prepared papillary muscles were placed in Tyrode solution that was continuously circulated and gassed with 95% O₂+5% CO₂at 32℃. The isolated papillary muscle was stimulated continuously with platinum pin electrode at frequency of 15/min and 90/min by means of electric stimulator and transmembrane action potentials were recorded with microelectrdes on the oscilloscope. The drug used was d-propranolol and its concentration was 0.5, 1.5 and 5.0 mg/L. The results obtained were as follows: 1. D-propranolol increased the threshold voltage of papillary muscle and raised by average of 213.6% of control. 2. D-propranolol had no effect on duration of action potential. 3. Conduction time of isolated papillary muscle was increased by d-propranolol and its effect was prominent at frequency of 90/min. 4. the maximum upstroke velocity was decreased by d-propranolol and its effect was dose-depndent decrease.

• Journal of Pharmaceutical Investigation
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• 제25권3호
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• pp.193-204
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• 1995

In order to examine the effect of extrahepatic cholestasis induced by common bile duct ligation on the hepatic function, the pharmacokinetics of antipyrine and d-propranolol were investigated in rats. In addition, in an attempt to observe the degree of direct hepatic injury, light and electron microscopic observations and conventional pathologic test using serum were performed. Five days after common bile duct ligation, antipyrine(15 mg/kg) and d-propranolol(3 mg/kg) were intravenously administrated to the rats, respectively. The total clearances of antipyrine and d-propranolol were significantly(p<0.05) decreased. Because hepatic clearance of antipyrine poorly extracted by the liver and that of d-propranolol highly extracted by the liver are respectively dependent on the hepatic intrinsic clearance and the hepatic blood flow, it may be concluded that extrahepatic cholestasis following five days after common bile duct ligation decreased the hepatic intrinsic clearance and the hepatic blood flow. SGPT, SGOT, cholesterol, bilirubin(total bilirubin, direct bilirubin) and alkaline phosphatase were significantly increased(p<0.05). The proliferation of bile ducts was prominent, and degeneration and necrosis of hepatocytes were observed by light microscope. Also, ultrastructurally, bile canaliculi were containing the amorphous materials and losing microvilli, and SER and RER in hepatocytes were dilated and vacuolated.

• 약학회지
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• 제28권5호
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• pp.265-273
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• 1984

The effects of cinnarizine, $Ca^{2+}-antagonist$, on the antihypertensive effect of coadministered ${\beta}-blockers$, propranolol and metoprolol, were investigated in SHR. Drugs were coadministered orally for 4 weeks. Hemodynamic and biochemical changes induced by above drugs were determined to elucidate their mechanism of action. a) Cardiohypertropy of SHR was significantly improved by the treatment of ${\beta}-blockers$ as well as combination with cinnarizine and ${\beta}-blockers$. b) $Mg^{2+}-contents$ were increased in ventricle and decreased in plasma and aorta in all of the groups, especially in the group of propranolol with cinnarizine. c) c-GMP contents in ventricle were increased when cinnarizine was coadministered with propranolol, and c-GMP contents in aorta were increased when cinnarizine was coadministered with metoprolol, camparing with propranolol or metoprolol alone-treated group. d) Plasma renin activity appeared to be increased in cinnarizine treated alone, but reduced by combination with ${\beta}-blockers$. e) Triglycerides and $Na^+$ contents in serum were decreased in the group of metoprolol with cinnarizine, comparing with metoprolol alone-treated group. Increased $K^+\;and\;Ca^{2+}$excretions in urine by ${\beta}-blockers$ were inhibited by cinnarizine, so $Na^+/K^+$ excretion ratios were increased. Diuretic effects was showed in metoprolol alone treated group, but reduced when coadministered with cinnarizine.

• Journal of Pharmaceutical Investigation
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• 제21권2호
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• pp.73-78
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• 1991

The influence of different suppository bases on the rectal absorption and the dissolution rate of propranolol was investigated. The bioavailability of propranolol in rectal suppository was determined by comparing the area under the concentration-time curves(AUC) for oral administration with rectal suppositories in rabbits. The dissolution $rates(D_{20min})$ were higher in such order as tween (TWE), witepsol H-15(WIT), polyethylene glycol(PEG) suppository. The maximum blood concentrations $(C_{max})$ were 803.9 ng/ml for TWE suppository, 770.2 ng/ml for WIT suppository, 281.2 ng/ml for PEG suppository and 177.1 ng/ml for oral administration. The relative bioavailabilities were 233.5% for TWE suppository, 218.1% for TWE suppository, 191.3% for PEG suppository. The correlation between $D_{20min}$ and AUC, the time for dissolution in 75% and $C_{max}$, the mean dissolution time and the mean residence time showed significant linear relationship respectively.

• Journal of Pharmaceutical Investigation
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• 제26권1호
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• pp.43-53
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• 1996

The objective of this study was to determine whether 4-phenylazobezyloxycarbonyl-Pro-Leu-Gly-Pro-D-Arg (Pz-peptide), an enhancer of hydrophilic solute permeability in the intestine, could elevate the paracellular permeability of hydrophilic drugs across cornea and conjunctiva in the rabbit. The in-vitro penetration of hydrophilic drugs (mannitol, atenolol) and lipophilic drug (propranolol) across the rabbit cornea and conjunctiva was studied either in the presence or absence of 3 mM Pz-peptide. Drug penetration was evaluated using the modified Ussing chamber. The conjunctiva was more permeable than the cornea to all drugs. Pz-peptide showed enhanced effects on the drug transport across cornea and conjunctiva in a concentration dependent manner. Effects or ion transport inhibitor on the mannitol penetration were then investigated. Mannitol penetration was not changed by serosal addition of $100\;{\mu}M$ ouabain, suggesting that $Na^+/K^+$ ion tranporter was not involved in the Pz-peptide induced elevation of paracellular drug permeability. Furthermore, effects of Pz-peptide and EDTA on the transport of atenolol and propranolol into the ocular tissues or blood circulation after its administration into both eyes were investigated. EDTA showed enhanced effect on propranolol transport into the ocular tissues, but Pz-peptide did not show significant difference. Systemic absorption of propranolol by the addition of EDTA or Pz-peptide was not changed. On the other hand, EDTA and Pz-peptide elavated the atenolol transport into the ocular tissues. The transport of atenolol into the blood circulation was also enhanced by the addition of EDTA, but no effect was observed by the addition of Pz-peptide. The above findings suggest that Pz-peptide would be used as an paracellular pathway enahncer of hydrophilic drugs into the eye, without affecting the systemic absortion of topically applied opthalmic drugs.

• 대한약리학회지
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• 제27권2호
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• pp.119-123
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• 1991

${\beta}-$수용체 효능약물 ((-)-NE), 길항약물 $((\pm)-propranolol,\;labetalol)$ 및 PDE 억제약물(imazodan, KR-30045, KR-30075 등)에 대한 ${\beta}-adrenoceptor$ binding 실험을 ${\beta}_1/{\beta}_2$ 비선택적 radioligand인 $(-)-[^3H]-DHA$를 사용하여 실시하였다. Saturation 실험에서 ${\beta}_1$ 및 ${\beta}_2$ 수용체를 모두 갖고 있는 rat 좌심실의 ${\beta}$ 수용체에 대한 $(-)-[^3H]-DHA$의 $K_d$ 값은 $1.5{\pm}0.43\;nM$, $B_{max}$는 $22.0{\pm}0.9\;fmol/mg$ protein이었다. $({\pm})propranolol$, labetalol 및 (-)NE는 단일상으로 $(-)-[^3H]-DHA$의 결합을 억제하였으며 Ki 값은 각각 $17.0{\pm}0.43\;nM$, $57.3{\pm}1.30\;nM$, $1.57{\pm}0.95\;{\mu}M$로 나타났다. 실험에 사용한 모든 PDE 억제약물들은 $(-)-[^3H]-DHA$ 결합을 $10^{-3}\;M$의 고농도에서도 10% 미만으로 억제했다. 실험결과, propraolol, labetalol 및 NE는 ${\beta}_1/{\beta}_2$ 수용체에 대해 비선택적인 약물로 나타났으며, imazodan 및 신합성 PDE 억제약물들은 rat 심근에 있는 ${\beta}-$수용체에 친화성이 거의 없음을 알 수 있었다.

• 대한수의학회지
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• 제27권1호
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• pp.35-40
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• 1987

Higenamine, a benzyltetrahydroisopuinoline analog isolated from aconite tuber, has potent isotropic action. Recent studies suggest it may have beta receptor agonistic property in that its inotropic action is blocked by propranolol in isolated rabbit heart. However, no study has been carried out on other organs than heart. Higenamine is expected to have pharmacological actions on smooth muscle on the ground that it has catecholamine moiety and tetrahydrosioquinoline nucleus in its chemical structure, both of which are well known to have smooth muscle relaxation effects. Therefore present study was aimed at determining whether higenamine has bronchodilating effect in isolated guinea pig trachea smooth muscle rich in adrenergic beta receptor and if any, it has agonistic effect on beta receptor. The results were summarized as follows : 1. Higenamine had remarkable bronchodilating effect in guinea pig tracheal smooth muscle in a dose-dependent manner. 2. Bronchodilator effect of higenamine in isolated guinea pig tracheal smooth muscle was blocked competitively by propranolol. The $pD_2$ value of higenamine in isolated guinea pig tracheal smooth muscle was 5.65 and the $pA_2$ value of propranolol against higenamine in the same preparation was 7.97.

• 대한의생명과학회지
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• 제15권4호
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• pp.287-293
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• 2009

Phospholipase D (PLD) is an enzyme hydrolyzing phosphatidylcholine to phosphatidic acid (PA) and choline. We investigated the involvement of PLD1 in the uptake of norepinephrine (NE) in PC12 cells, pheochromocytoma cells. NE uptake was specific in PC12 cells because nomifensine, a specific blocker of NE transporter, blocked NE uptake. Inhibition of PLD function in PC12 cells by the treatment of butanol suppressed the NE uptake. In contrast, overexpression of PLD1 in PC12 cells increased NE uptake efficiently. These results suggest that PLD activity is involved in NE uptake. We explored the action mechanism of PLD in NE uptake. PA phosphatase inhibitor, propranolol, blocks the formation of PKC activator diacylglycerol from PA. Propranolol treatment to PC12 cells blocked dramatically the uptake of NE. Specific PKC inhibitors, GF109203X and Ro31-8220, blocked NE uptake. Taken together, we suggest for the first time that PLD1 activity is involved in NE uptake via the activation of PKC.

• 동의생리병리학회지
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• 제17권3호
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• pp.648-655
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• 2003

In this study, the effects of Gamgung-tang gamibang on the hyperthyroidism induced by the intraperitoneal injection of 3,5,3-triiodothyronine was examined by the measurement of physical changes, body weight, the volume of food intake and rectal temperature, and heart weight, heart beat, blood pressure with contrast to propranolol, one of beta-blocking agents. the obtained results were as follows. The Gamgung-tang gamibang extract showed to inhibit the decrease of body weight and rectal temperature, and decrease the food intake, so the inhibitory effects of Gamgung-tang gamibang extract on the experimental hyperthyroidism were exhibited. The Gamgung-tang gamibang extract showed the inhibitory effects on the circulatory functions changed and enhanced by the experimental induced hyperthyroidism, the action of Gamgung-tang gamibang extract was less effective than the propranolol of D-CONT group. The Gamgung-tang gamibang extract showed significant effects to inhibit the concentration of serum thyroid houmone, more effective than the propranolol, beta-blocking agents. The Gamgung-tang gamibang extract showed the effective inhibitory reaction on the biochemical changes in serum, cholesterol, ketone bodies, free fatty acid, glucose in hyperthyroid rats induced by 3,5,3-triiodothyronine.

• The Korean Journal of Physiology
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• 제24권1호
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• pp.39-49
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• 1990

bombesin의 생물학적 활성중 하나는 위장관의 평활근을 수축시키는 작용이다. 그러므로, 본 실험에서는 bombesin이 위장관의 운동성과 관계가 깊은 평활근의 전기적 활동에 미치는 영향과 신경기전을 밝히고자 하였다. 고양이 60마리로부터 urethane마취하에 위를 적출한 다음 대만 쪽에서 체부와 유문부가 포함된 평활근 절편을 얻었으며 또한 체부에서 윤상근 절편을 얻었다. 평활근 절편을 Krebs-Ringer 용액으로 채워진 기록용기에 넣고 Ag-AgCl전극을 사용하여 체부와 유문부에서 서파를 기록하는 한편 윤상근 절편의 자발적 수축을 기록하였다. 기록용기 속의 용액에는 5% $Co_{2}$를 내포한 $O_{2}$를 계속 공급하였으며, 용액의 온도는 $36^{\circ}C$가 유지되도록 하였다. 기록용기 속에서 1시간 동안 안정시킨 다음 서파빈도와 수축빈도가 일정하여지면 bombesin과 그 유도체, substance P와 그 유도체 그리고 몇가지 종류의 신경차단제를 각각 투여하여 다음과 같은 결과를 얻었다. 1) bombesin은 $10^{-9}\;M$에서부터 $3\;{\times}\;10^{-8}\;M$ 사이의 농도에서 서파빈도와 수축빈도를 농도-의존적으로 증가시켰다. 2) bombesin 유도체인 $D-leu^{13}-{\psi}\;(CH_{2}NH)-D-leu^{14}-bombesin$은 서파빈도를 증가시키는 bombesin의 작용을 억제하였다. 3) 서파빈도를 증가시키는 bombesin의 작용에 대하여 tetrodotoxin과 hexamethonium은 억제적으로 작용하였으나 atropine, phentolamine 그리고 propranolol은 이렇다할 영향을 비치지 않았다. 4) 서파빈도를 증가시키는 bombesin의 작용에 대하여 substance P 유도체인 $D-pro^{2}-D-trp^{7,9}-substance\;P$는 억제적으로 작용하였다. 5) sunstance P 자체는 서파빈도에는 영향을 미치지 않았다. 이상의 결과로 보아 (1) bombesin은 적출한 고양이 위 평활근의 서파빈도와 체부 윤상근의 수축빈도를 증가시키며, (2) bombesin은 신경-근 연접에서 acetylcholine이나 noradrenalin을 신경전달물질로 사용하지 않는 내원성 신경을 거쳐 서파빈도를 증가시키는 것으로 생각된다. (3) 그러나, bombesin이 서파의 발생빈도를 증가시키는 과정에 substance P를 신경전달물질로 사용하는 신경이 개재하는 것 같지는 않았다.