• 동의생리병리학회지
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• 제22권1호
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• pp.148-154
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• 2008

The butanol extract of Euonymus alatus (BEA) induced dose-dependent relaxation of phenylephrine-precontracted aorta, which was abolished by removal of functional endothelium. Pre-treatment of the endothelium-intact aortic tissues with $N^G-nitro-L-arginine methylester$ (L-NAME), and 1 H-[1,2,4]-oxadiazole- [$4,3-{\alpha}$]-quinoxalin-1-one (ODQ) inhibited the relaxation induced by BEA, respectively. BEA-induced vascular relaxation was not blocked by glibenclamide, tetraethylammonium (TEA), indomethacin, atropine, propranolol, verapamil, and diltiazem, respectively. Moreover, BEA inhibits phenylephrine-induced vascular constriction in a dose-dependent manner. These results suggest that BEA relaxes vascular smooth muscle via endothelium-dependent nitric oxide/cGMP signaling.

• 한국식물생명공학회:학술대회논문집
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• 한국식물생명공학회 2004년도 생명공학 실용화를 위한 비젼
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• pp.74-79
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• 2004

Little is known about the effect of epigallocatechin-3 gallate (ESCG), a major constituent of green tea, on the expression of cyclooxygenase (COX)-2. Here, we studied the role of phospholipase D (PLD) isozymes in EGCG-induced COX-2 expression. Stimulation of human astrocytoma cells (U87) with EGCG induced formation of phosphatidylbutanol, a specific product of PLD activity, and synthesis of COX-2protein and its product, prostaglandin $E_2$ ($PGE_2$). Pretreatment of cells with 1-butanol, but not 3-butanol, suppressed EGCG-induced COX-2 expression and $PGE_2$ synthesis. Furthermore, evidence that PLD was involved in EGCG-induced COX-2 expression w3s provided by the observations that COX-2 expression was stimulated by over-expression of PLD1 or PLD2 isozymes and treatment with phosphatidic acid(PA), and that prevention of PA dephosphorylation by 1-propranolol significantly potentiated COX-2expression Induced by EGCG. EGCG induced activation of p38 mitogen-activated protein kinase (p38MAPK), and specific Inhibition of p38 MAPK dramatically abolished EGCG-Induced PLD activation, COX-2 expression, and $PGE_2$ formation. Moreover, protein kinase C (PKC) inhibition suppressed EGCG-induced p38 MAPK activation, COX-2 expression, and $PGE_2$ accumulation. The same pathways as those obtained in the astrocytoma cells were active in primary rat astrocytes, suggesting the relevance of the findings. Collectively, our results demonstrate for the first time that PLD isozymes mediate EGCG-induced COX-2 expression through PKC and p38 in immortalized astroglial line and normal astrocyte cells.

• Journal of Chest Surgery
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• 제24권7호
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• pp.637-646
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• 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.

• 대한한의학방제학회지
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• 제10권2호
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• pp.143-158
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• 2002

The purpose of the present study is to determine the effect of Jakyakgamchotang on histamine or acetylcholine induced tracheal smooth muscle contraction in rats and guinea pigs. Guinea pig(500g, male) and Sprague Dawley rats(250g, male) were killed by $CO_2$ exposure and a segment (4-5mm) of the thoracic trachea from each rat and guinea pig was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of histamine(His) which evoked 50% of maximal response($ED_{50}$) was obtained from cumulative dose response curves for histamine($10^{-7}{\sim}10^{-4}M$). Contractions evoked by His($ED_{50}$) were inhibited significantly by Jakyakgamchotang. In guinea pig tracheal smooth muscle, the mean percent inhibition of histamine induced contraction was 90.8% (p〈0.001) after $100{\mu}l/ml$ Jakyakgamchotang. In rat tracheal smooth muscle, the mean percent inhibition of acetylcholine induced contraction was 22.1% (p〈0.05) after $100{\mu}l/ml$ Jakyakgamchotang. Propranolol indomethacin and methylene blue($10^{-7}M$) slightly but significantly attenuated the inhibitory effects of Jakyakgamchotang. These results indicate that Jakyakgamchotang can relax histamine or acetylcholine induced contraction of guinea pig and rat tracheal smooth muscle.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.675-680
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• 2002

In order to investigate the underlying mechanism of HCI in oesophagitis, the inflammatory response to HCI was observed in RBL-2H3 mast cells. Rat basophilic leukemia (RBL-2H3) cells were used to measure histamine release, arachidonic acid (AA) release, reactive oxygen species (ROS) and peroxynitrite generation induced by HCI. Exogenous HCl increased the level of histamine release and ROS generation in a dose dependent manner, whereas it decreased the spontaneous release of [$^3$H] M and the spontaneous production of peroxynitrite. Mepacrine (10 $\mu$M), oleyloxyethyl phosphorylcholine (10 $\mu$M) and bromoenol lactone (10 $\mu$M) did not affect both the level of histamine release and ROS generation induced by HCI. U73122 (1 $\mu$M), a specific phospholipase C (PLC) inhibitor did not have any influence on level of histamine release and ROS generation. Propranolol (200 $\mu$M), a phospholipase D (PLD) inhibitor, and neomycin (1 mM), a nonspecific PLC and PLD inhibitor, significantly inhibited both histamine release and ROS generation. Diphenyleneiodonium (10 $\mu$M), a NADPH oxidase inhibitor, and tiron (5 mM), an intracellular ROS scavenger significantly inhibited the HCI-induced histamine release and ROS generation. These findings suggest that the inflammatory responses to HCI is related to histamine release and ROS generation, and that the ROS generation by HCI may be involved in histamine release via the PLD pathway in RBL-2H3 cells.

• 대한수의학회지
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• 제31권3호
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• pp.253-258
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• 1991

The aims of this study were to investigate the effect of adenosine triphosphate (ATP), which has been known as the neurotransmitter of nonadrenergic, noncholinergic nerves, and the source of $Ca^{\sharp}$ in the effect of ATP on the isolated renal artery of pig. The results of this study were summarized as follows: 1. ATP caused the contraction and the contractile responses were increased in a dose-dependent manner between the concentration of ATP $2{\times}10^{-3}M$ and $10^{-2}M$ on the isolated renal artery of pig. 2. The contractile responses induced by ATP $(5{\times}10^{-3}M)$ were not blocked by pretreatment with cholinergic receptor blocker (atropine, $10^{-6}M$), $\alpha$-adrenergic recptor blocker(phentolamine, $10^{-6}M$) or $\beta$-adrenergic receptor blocker (propranolol, $10^{-6}M$), and $H_1$-receptor blocker (pyrilamine, $10^{-6}M$) or $H_2$-receptor blocker (cimetidine, $10^{-6}M$) on the isolated renal artery of pig. 3. The contractile responses induced by ATP $(5{\times}10^{-3}M)$ were not appeared in $Ca^{\sharp}$-free medium. As the concentration of $Ca^{\sharp}$ in $Ca^{\sharp}$-free medium was increased, the contractile responses induced by ATP $(5{\times}10^{-3}M)$ were enhanced but were completely inhibited by pretreatment with $Ca^{\sharp}$-channel blocker, papaverine $(5{\times}10^{-5}M)$ or verapamil $(5{\times}10^{-5}M)$ on the isolated renal artery of pig.

• 대한수의학회지
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• 제40권2호
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• pp.291-299
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• 2000

Magnesium ($Mg^{2+}$) transport across the plasma membrane of cardiac myocytes appears to be under hormonal control. Repeated stimulations with adrenergic or histaminergic agonist produced a progressive decrease in $Mg^{2+}$ efflux from hearts. Thus we hypothesized that the $Mg^{2+}$ efflux may be resulted from a down-regulation of receptors or from a depletion of $Mg^{2+}$ from intracellular pool(s) in the hearts. In the present study, the regulation of $Mg^{2+}$ homeostasis by receptor stimulation was studied in perfused rat and guinea pig hearts. The successive short addition of norepinephrine (NE) to rat and guinea pig, and of histamine (HT) to perfused guinea pig hearts induced a progressive decrease in $Mg^{2+}$ efflux. These $Mg^{2+}$ effluxes were blocked by propranolol or ranitidine, respectively. These decrease in $Mg^{2+}$ efflux were inhibited by sodium cyanide (NaCN), which increases intracellular $Mg^{2+}$ ($[Mg^{2+}]_i$) levels. When NE (or HT) was added after HT (or NE), this efflux was also decreased in the guinea pig hearts. In the rat hearts and myocytes, HT did not stimulate $Mg^{2+}$ efflux. But NE produced a large $Mg^{2+}$ efflux after stimulation with HT. 8-(4-Chlorophenylthio)-adenosine cAMP (cAMP), like NE and HT, also induced a progressive decrease in $Mg^{2+}$ efflux in guinea pig hearts. This effect was inhibited by NaCN. These data provide evidence that the progressive decrease in receptor-stimulated $Mg^{2+}$ efflux is considered to be due to a decrease in $[Mg^{2+}]_i$ levels rather than receptor down-regulation.

• The Korean Journal of Physiology
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• 제20권2호
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• pp.165-174
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• 1986

The voltage clamp studies were undertaken to elucidate the properties of the slow inward current, $i_{si}$, in the small preparations of the rabbit sinoatrial node. The slow inward current, $i_{si}$, which is known to be responsible for the late one-third of pacemaker potential and whole range of upstroke phase of action potential was analysed with the effects of isoprenaline, cobalt, ouabain and higenamine. The results obtained are as follows; 1) Voltage of SA node preparation was held at zero current level, usually-40mV and the slow inward current, $i_{si}$, was activated by depolarizing clamp pulses. Peak values of $i_{si}$, in steady state were at $-10{\pm}0mV$ in most preparations. 2) Isoprenaline, ${\beta}-agonist$ increased $i_{si}$ and no shift was noticed in voltage-dependency. 3) Cobalt ion in the concentration of 1 mM abolished is, in entire range of membrane potential and the difference of two current levels before and after $Co^{2+}$ treatment could be considered as pure $i_{si}$ magnitude. 4) In the therapeutic concentration of ouabain $(5{\times}10^{-8}M)$ slightly increased is, and reduced the time to reach the peak value. 5) Higenamine $(10^{-6}M)$ changed the configurations of action potential (i. e. rapid upstroke phase and notch in the spike) and increase spontaneous rate. It also increased is, and the effect of higenamine was blocked ${\beta}-blocker$, propranolol $(10^{-6}M)$.

• Korean Journal of Acupuncture
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• 제17권1호
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• pp.67-73
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• 2000

The purpose of the present study is to determine the effect of Radix Stemonae on histamine induced tracheal smooth muscle contraction in guinea pigs. Guinea pig(500g, male) were killed by $CO_2$ exposure and a segment (8-10mm) of the thoracic trachea from guinea pig was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of histamine (His) which evoked 50% of maximal response ($ED_{50}$) was obtained from cumulative dose response curves for histamine ($10^{-7}∼10^{-4}M$). Contractions evoked by His ($ED_{50}$) were inhibited significantly by Radix Stemonae. In guinea pig tracheal smooth muscle, the mean percent inhibition of histamine induced contraction was 87.4% (p<0.01) after $100{\mu}l/ml$ Radix Stemonae. Following treatment with propranolol, the mean percent inhibition caused by $100{\mu}l/ml$ Radix Stemonae fell to 16.2% in guinea pig induced by histamine contraction. Indomethacin and methylene blue($10^{-7}M$) did not significantly alter the inhibitory effect of Radix Stemonae. These results indicate that Radix Stemonae can relax histamine induced contraction of guinea pig tracheal smooth muscle, and that this inhibition involves sympathetic effects.

• The Korean Journal of Physiology
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• 제22권1호
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• pp.31-39
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• 1988

This study was carried out to investigate the action of adenosine triphosphate (ATP) on the motility of immature pig uterine smooth muscle. ATP appeared contractile responses in a dose-dependent manner, showing the maximal contraction at the concentration of $10^{-3}M$ in the uterine smooth muscle strip. The contractile responses by $ATP(10^{-4}M)$ were not affected by atropine $(10^{-6}M)$, phentolamine $(10^{-6}M)$, propranolol $(10^{-6}M)$, pyrilamine $(10^{-6}M)$, cimetidine $(10^{-6}M)$, and theophyulline $(5{\times}10^{-5}M)$, but were inhibited uncompetitively by quinidine. The effects of these drugs on the contractile responses by prostaglandin $F_{2{\alpha}}(PGF_{2{\alpha}})$ were also comparable to those observed with ATP. When muscle strips were pretreated with indomethacin $(5{\times}10^{-5}M)$ for 20 min., the contractile responses by $ATP(10^{-4}M)$ were completely inhibited. But the contractile responses by $PGF_{2{\alpha}}$ were not affected by indomethacin. These results suggest that ATP elicited the contraction through noncholinergic- and nonadrenergic-receptor mediated by prostaglandin $F_{2{\alpha}}$ in pig uterine smooth muscle.