• The Journal of the Korean dental association
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• v.16 no.7 s.110
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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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• v.25 no.3
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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.

• YAKHAK HOEJI
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• v.28 no.5
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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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• v.21 no.2
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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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• v.26 no.1
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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.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.119-123
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• 1991

${\beta}-Adrenoceptor$ binding study of ${\beta}-agonist$ ((-)NE), ${\beta}-antagonists$ $(({\pm})\;propranolol,\;labetalol)$ and PDE inhibitors (imazodan, KR-30045, KR-30075 etc.) was performed using $(-)-[^3H]-DHA$, as a $non-{\beta}_1/{\beta}_2$ selective radioligand. In saturation studies, $K_d$ and $B_{max}$ of $(-)-[^3H]-DHA$ to ${\beta}-adrenoceptors$ in rat left ventricle in which both ${\beta}_1$ and ${\beta}_2$ receptors coexist were determined to be $1.5{\pm}0.43\;nM$ and $22.0{\pm}0.9\;fmol/mg$ protein, respectively. $({\pm})Propranolol$, labetalol and (-)NE competed for $(-)-[^3H]-DHA$ binding sites in an essentialy monophasic manner with $Ki=17.0{\pm}0.40\;nM,\;57.3{\pm}1.30\;nM,\;and\;1.57{\pm}0.95\;{\mu}M$, respectively. All of PDE inhibitors inhibited the $(-)-[^3H]-DHA$ binding by only below 10% even at the high concentration of $10^{-3}M$. The present results suggest that propranolol, labetalol and NE are $non-{\beta}_1/{\beta}_2$ selective antagonists and agonist, respectively. Additionally, this study shows that imazodan and new synthesized PDE inhibitors may hardly have the affinities to ${\beta}-adrenoceptors$ in cardiac muscle.

• Korean Journal of Veterinary Research
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• v.27 no.1
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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.

• Biomedical Science Letters
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• v.15 no.4
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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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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• v.24 no.1
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• pp.39-49
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• 1990

It has been reported that bombesin induces contraction of the smooth muscle of the gastrointestinal tract. Thus, the present investigation was undertaken to see an influence of bombesin on electrical activity of the gastric smooth muscle, since electrical activity is associated with contractile activity in the smooth muscle of the stomach. Smooth muscle strips $(5\;{\times}\;1.5\;cm)$ that included the corpus and antrum were prepared from the ventral and dorsal portion of the feline stomach along the greater curvature. Circular muscle strips $(1\;{\times}\;0.3\;cm)$ of the corpus were also obtained. Electrical activity of the corpus and antrum of the muscle strip was monophasically recorded by using Ag-AgCl capillary electrodes placed on the circular muscle layer. Contractile activity of the circular muscle strip was also recorded. The recordings were performed in Krebs-Ringer solution that was continuously aerated with $O_{2}$ containing 5% $Co_{2}$, and kept at $36^{\circ}C$. Dose-related responses of electrical activity and contractility to bombesin was studied after frequency of slow waves and contraction of each strip reached to a steady state. An action of $D-leu^{13}-{\psi}\;(CH_{2}NH)-D-leu^{14}-bombesin,\;D-pro^{2}-D-trp^{7,9}-substance\;P$, tetrodotoxin, hexamethonium, atropine, phentolamine or propranolol on the effect of bombesin was also observed. 1) Bombesin increased frequency of slow waves and contractions dose-dependently at concentrations from $10^{-9}\;M\;to\;3\;{\times}\;10^{-8}\;M$. 2) The bombesin analogue at a concentration of $3\;{\times}\;10^{-7}\;M$ antagonized the effect of bombesin on frequency of slow waves. 3) The effect of bombesin on frequency of slow waves was inhibited by tetrodotoxin $(10^{-6}\;M)$ and hexamethonium $(10^{-3}\;M)$ but unaffected by atropine $(10^{-6}\;M)$, phentolamine $(10^{-5}\;M)$ and propranolol $(10^{-5}\;M)$. 4) The effect of bombesin on frequency of slow waves was blocked by the substance P analogue at a concentration of $10^{-5}\;M$. 5) Substance P at a concentration of $10^{-5}\;M$ failed to change frequency of slow waves. It is concluded from the above results that bombesin increases the frequency of slow waves as well as contractions of the smooth muscle strip from the feline stomach, and the effect of bombesin might be mediated by non-cholinergic or non-adrenergic mechanism at neuromuscular junction. However, enteric nerves that have substance P as a neurotransmitter do not appear to participate in the action of bombesin on frequency of slow waves.