• 동의생리병리학회지
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• 제16권5호
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• pp.1060-1065
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• 2002

LC20 phosphorylation and PKC α play an important role in modulation of contractile activity of smooth muscle. Besides, myosin phosphatase is also related with smooth muscle contraction in signaling pathways. We previously demonstrated that Crataegi Fructus inhibited phenylephrine-induced contraction and which might be implicated in nitrite formation(Son et al., 2002). In this study, we investigated the effects of butanol fraction of Crataegi Fructus(BFFC) on the localization of α-protein kinease C(PKC α) and myosin phosphatase subnits(MPs) in freshly isolated single ferret potal vein cells, and phosphorylation of LC20 during phenylephrine stimulation. In PKC α and MPs localization, BFFC blocked its translocation from the cytosol to the cell membrane by treatment of phenylephrine. BFFC have also dephosphorylated LC20 phosphorylation by phenylephrine stimulation under basal level, but no significant. These results indicate that the relaxation effect of BFFC is associated with inhibition of PKC α activation and MPs dissociation, and thus myosin phosphatase activity may be increased.

• 약학회지
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• 제50권4호
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• pp.293-299
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• 2006

The aim of present study was to investigate the possible influence of Rho-kinase inhibition on the plant-derived estrogen-like compounds-induced arterial relaxation. Agonist- or depolarization-induced vascular smooth muscle contractions involve the activation of Rho-kinase pathway. However there are no reports addressing the question whether this pathway is involved in genistein-or daidzein-induced vascular relaxation in rat aortae precontracted with phenylephrine or thromboxane $A_2$ mimetic U-46619. We hypothesized that Rho-kinase inhibition plays a role in vascular relaxation evoked by genistein or daidzein in rat aortae. Endothelium-intact and denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Genistein concentration-dependently inhibited phenylephrine or thromboxane $A_2-induced$ contraction regardless of endothelial function. Surprisingly, in the agonists-induced contraction, similar results were also observed in aortae treated with daidzein, the inactive congener for protein tyrosine kinase inhibition, suggesting that Rho-kinase might act upstream of tyrosine kinases in phenylephrine-induced contraction. In conclusion, in the agonists-precontracted rat aortae, genistein and daidzein showed similar relaxant response regardless of tyrosine kinase inhibition or endothelial function.

• The Korean Journal of Physiology and Pharmacology
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• 제21권4호
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• pp.407-413
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• 2017

Vascular reactivity can be influenced by the vascular region, animal age, and pathologies present. Prostaglandins (produced by COX-1 and COX-2) play an important role in the contractile response to phenylephrine in the abdominal aorta of young rats. Although these COXs are found in many tissues, their distribution and role in vascular reactivity are not clear. At a vascular level, they take part in the homeostasis functions involved in many physiological and pathologic processes (e.g., arterial pressure and inflammatory processes). The aim of this study was to analyze changes in the contractile response to phenylephrine of thoracic/abdominal aorta and the coronary artery during aging in rats. Three groups of rats were formed and sacrificed at three distinct ages: prepubescent, young and old adult. The results suggest that there is a higher participation of prostanoids in the contractile effect of phenylephrine in pre-pubescent rats, and a lower participation of the same in old rats. Contrarily, there seems to be a higher participation of prostanoids in the contractile response of the coronary artery of older than pre-pubescent rats. Considering that the changes in the expression of COX-2 were similar for the three age groups and the two tissues tested, and that expression of COX-1 is apparently greater in older rats, COX-1 and COX-2 may lose functionality in relation to their corresponding receptors during aging in rats.

• 대한수의학회지
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• 제33권2호
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• pp.199-209
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• 1993

The effects of ${\alpha}_1$-adrenergic stimulation on membrane potential, intracellular sodium activity $(a_N{^i{_a}})$, and contractility were investigated in the isolated papillary muscle of euthyroid, hyperthyroid, and hypothyroid guinea pigs. Cardiac alterations in the thyroid state have been shown to induce marked changes in action potential characteristics, the most pronounced shortening of action potential duration by hyperthyroidism and an increase in duration by hypothyroidism. $10^{-5}M$ Phenylephrine produced a decrease in $(a_N{^i{_a}})$ in euthyroid and hypothyroid preparations, but an increase in $(a_N{^i{_a}})$ in hyperthyroid ones. The major findings were that phenylephrine produced a stronger positive inotropic effect(PIE) without initial negative inotropic effect(NIE) in hyperthyroid preparations, while phenylephrine produced markedly NIE in hypothyroid ones. The alterations in membrane potential, $(a_N{^i{_a}})$, and contractility were abolished by $3{\times}10^{-5}M$ prazosin in hypothyroidism. In hypothyroid ventricular muscle, the decrease in $(a_N{^i{_a}})$ caused by phenylephrine were not abolished or reduced by $10^{-5}M$ strophanthidin, $10^{-5}M$ TTX, $3{\times}10^{-4}M$ lidocaine, or $100^{-5}M$ verapamil. These results indicate that the ${\alpha}_1$-adrenoceptor-mediated decrease in $(a_N{^i{_a}})$ is not associated with a stimulation of the $Na^+$-$K^+$ pump, inhibition of the $Na^+$ or $Ca^+$ channel in hypothyroid ventricular muscle. $10^{-5}M$ Phenylephrine decreased $(a_N{^i{_a}})$ but increased $(a_N{^i{_a}})$ in the presence of a PKC activator phorbol dibutyrate$(PDB_u)$. In conclusion, it is suggested that the following sequence of events in response to phenyleplhane occur in guinea pig ventricular muscle. First, changes in thyroid state may contribute to the ventacular electrophysiological propeties or ion transport system. Second, the adrenoceptor-mediated initial transient NIE may be associated with the decrease in $(a_N{^i{_a}})$ by PKC activation.

• 대한한방내과학회지
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• 제22권2호
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• pp.119-125
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• 2001

Objectives : This study was conducted to evaluate the effect and mechanism of Geupoongjibo-dan's relaxation of the tension of the blood vessel caused by Phenylephrine and KCI. Methods : In order to study the effect of Geupoongjibo-dan's relaxation of the blood vessel tension, Geupoongjibo-dan extract was infused into Phenylephrine and KCI-induced contracted rabbit aorta strips. To analyze the mechanism of Geupoongjibo-dan's effect on the blood vessel, Geupoongjibo-dan extract infused into Phenylephrine and KCI-induced contracted strips induced by agonists after treatment of N${\omega}$-nitro-L-arginine, Methylene Blue. Results : 1. Geupoongjibo-dan was very effective in relaxing the blood vessels contracted by Phenylephrine. 2. Geupoongjibo-dan was effective against Phenylephrine, than against KCI. 3. Geupoongjibo-dan's more relaxation effect on a blood vessel was terminated by N${\omega}$-nitro-L-arginine and methylene treatment. Conclusion : THis study showed that Geupoongjibo-dan's relaxation effect on a blood vessel is irrelevant to ${\alpha}$-adrenalin receptor, and it relaxes contracted vessels through cGMP channel.

• 대한약리학회지
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• 제10권1호
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• pp.31-40
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• 1974

기니아-픽 및 백서정관(白鼠精管)에 대(對)한 $PGE_1$의 작용(作用)과 이들 조직(組織)에 있어서 교감신경효능제(交感神經效能劑)의 작용(作用)에 미치는 $PGE_1$의 효과(效果)를 보고 나아가서 계양막(鷄羊膜)에 대(對)한 $PGE_1$의 작용(作用)을 관찰(觀察)하였다. 1. 기니아-픽 적출정관표본(摘出精管標本)에서 $PGE_1$전처치(前處置)에 의(依)하여 phenylephrine이나 norepinephrine의 작용(作用)이 증강(增强)되었으며, 하복신경(下腹神經)-근표본(筋標本)에서 신경자극(神經刺戟)이나 trans-mural stimulation에 의(依)한 수축(收縮)에 미치는 phenylephrine, norepinephrine 및 tyratnine의 작용(作用)이 $PEG_1$ 전처치(前處置)에 의(依)하여 증강(增强)되었다. 특히 긴장상승(緊張上昇)이 현저(顯著)하였다. 2. 백서정관(白鼠精管)의 하복신경(下腹神經)-근표본(筋標本)에서는 기너아-픽 정관(精管)에서와는 달리 $PGE_1$을 처리(處理)함으로써 신경자극(神經刺戟) 및 transmural stimulation에 의(依)한 수축고(收縮高)가 서서(徐徐)히 감소(減少)되고, $PGE_1$을 전처치(前處置)한 후(後)에도 $10^{-6}g/ml$ phenylephrine 또는 norepinephrine에 의(依)한 긴장상승(緊張上昇)이나 수축고(收縮高)의 증가(增加)는 나타나지 아니 하였다. 3. 신경섬유(神經纖維)가 제거(除去)된 기니아-픽정관(精管)에 있어서는 $PGE_1$ 전처치(前處置)에 의(依)하여 phenylephrine 또는 norepinep. hrine의 작용(作用)이 증가(增加)되나 denervation 된 백서(白鼠)의 정관(精管)에 있어서는 $PGE_1$ 처리(處理)로서는 norepinephrine의 작용(作用)에 하등(何等)의 영향(影響)을 주지 아니 하였다. 4. 계양막평활근(鷄羊膜平滑筋)의 자발운동(自發運動)은 저농도(低濃度) $PGE_(10^{-8}g/ml)$에 의(依)하여 거의 변화(變化)를 받지 아니 하나, 농도(濃度)가 增加(增加)함으로서 자발운동(自發運動)은 불규칙(不規則)하나 대체(大體)로 억제적(抑制的)으로 나타났었고, $PGE_1$ 전처치후(前處置後) 고농도(高濃度) phenylephrine을 작용(作用)시켰으나 구등(?等)의 영향(影響)을 받지 아니 하였고 physostigmine의 작용(作用)은 길항(拮抗하였다. 이상(以上)의 결과(結果)로 보아 $PGE_1$은 동물(動物)의 정관(精管)에 대(對)한 작용(作用)에는 종(種)의 차이(差異)가 있으며 $PGE_1$은 교감신경효능제(交感神經效能劑)에 의(依)한 기니아-픽 정관수축작용(精管收縮作用)에 대(對)하여 supersensitivity를 야기(惹起)시켰으며, 이는 정관평활근(精管平滑筋)에 대(對)한 직접작용(直接作用)이 아닌 다른 작용기전(作用機轉)에 기인(基因)할 것으로 사료(思料)되는 바이다.

• Archives of Pharmacal Research
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• 제19권5호
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• pp.386-389
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• 1996

The in vivo behaviour of phenylephrine hydrochloride in different vehicles like gels of Carbopol $907^circledR$, Carbopol $934P^circledR$ and latex system of cellulose acetate hydrogen phthalate(CAHP) was evaluated by measuring the reduction in intraocular pressure and the mydriatic activity. The parameters that haave been utilised to assess the performance of the formulations were the area under the curve (AUC), the maximum mydriasis $(I_{max})$, ethe time of maximum response $(T_{max})$ and the duration of activity (D). The influence of viscosity and mucoadhesion on the bioavailability parameters has also been investigated. Carbopol 934P and CAHP formulations showed prolonged duration of action and greater AUC compared to Carbopol 907 aqueous solution(P<0.05).

• 대한수의학회지
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• 제36권2호
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• pp.327-335
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• 1996

Recently in spite of the interest on the regulation of intracellular $Mg^{2+}$ by neurotransmitters or drugs, the magnesium ion($Mg^{2+}$) regulation by ${\alpha}_1$-adrenoceptor stimulation has not been studied in the heart yet. To elucidate the regulation of ${\alpha}_1$-adrenoceptor stimulation-induced $Mg^{2+}$ release and the effects of ${\alpha}_1$-adrenoceptor stimulation on pathophysiological conditions, in this study we have evaluated the effects of phenylephrine, PMA, $H_7$. staurosporine, verapamil and lidocaine on $Mg^{2+}$ release in perfused guinea pig heart. During preperfusion exogenous $Mg^{2+}$ was added to the medium to give 1.2mM 15min before starting to addition of drugs, and then the infusion of exogenous $Mg^{2+}$ was stopped. $Mg^{2+}$ in the perfusate leaving the heart was measured by atomic absorption spectrophotometry. $Mg^{2+}$ free solution produced an increase in heart rate and phenylephrine elicited $Mg^{2+}$ release from the heart. $Mg^{2+}$ release by phenylephrine was abolished by combined treatment with prazosin. By contrast, cardiac $Mg^{2+}$ uptake induced by a protein kinase C(PKC) activator, PMA was abolished by a selective PKC inhibitor, staurosporine. And the phenylephrine-induced $Mg^{2+}$ release was not affected by the PKC inhibitor, $H_7$. When verapamil or lidocaine was added to perfusing solution, $Mg^{2+}$ release was potentiated by phenylephrine from perfused guinea pig heart. These results suggest that ${\alpha}_1$-adrenoceptor stimulation caused $Mg^{2+}$ release and that PKC is not involved in ${\alpha}_1$-adrenoceptor mediated $Mg^{2+}$ release from perfused guinea pig heart. Under pathophysiological conditions, the $Mg^{2+}$ alteration by ${\alpha}_1$-adrenoceptor stimulation is considerable.

• 대한약리학회지
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• 제32권2호
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• pp.189-199
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• 1996

Myocardial ${\alpha}_1-adrenoceptors$ have been shown to mediate a biphaslc inotropic response that was characterized by a transient decline followed by a sustained increasing phase in guinea pig ventricular muscle. Recently one group reported that an ${\alpha}_1-adrenoceptors-induced$ intracellular $Na^+$ decrease is linked to fast $Na^+$ channel inhibition and another group reported that it is linked to $Na^+$-$K^+$ pump activation by ${\alpha}_{1b}-adrenoceptors$. But until now, its mechanism is not clear. Therefore, to see whether the $Na^+$channel or $Na^+-K^+$ pump is related to a decrease in intracellular $Na^+$ activity and/or the negative inotropic response, and which ${\alpha}_1-adrenoceptor$ subtype was involved in the decrease in intracellular $Na^+$activity by phenylephrine, we used conventional and sodium selective microelectrodes, and tension transducer to determine the effects of ${\alpha}_1-adrenergic$ stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force in guinea pig ventricular muscles. $10^{-5}$ M Phenylephrine produced a slight hyperpolarization of the diastolic membrane potential, a decrease or increase in $a_N^i_a$, and a biphasic inotropic response. The negative inotropic response accompanied by a decrease in intracellular $Na^+$activity, whereas in muscles showing a remarkable positive inotropic response without initial negative inotropic effect was accompanied by an increase in intracellular $Na^+$ activity. The decrease in intracellular $Na^+$ activity was apparently inhibited by WB4101, an antagonist of the ${\alpha}_{1a}-adrenoceptors$. The decrease in intracellular $Na^+$ activity caused by phenylephrine was not abolished or reduced by a block of the fast $Na^+$ channels. $V_{max}$ also was not affected by phenylephrine. Phenylephrine produced an increase in intracellular $Na^+$ activity in the presence of a high concentration of extracellular $Ca^{2+}$ (in quiescent muscle) or phorbol dibutyrate, a protein kinase C activator(in beating muscle). These suggest that the ${\alpha}_{1a}-adrenoceptors-mediated$ decrease in intracellular $Na^+$ activity may be related to the protein kinase C.

• 대한약리학회지
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• 제29권1호
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• pp.65-72
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• 1993

자외선조사는 흰쥐흉부대동맥의 휴지기장력에 거의 영향을 미치지 못했으나, phenylephrine으로 수축된 표본에서는 자외선조사로 내피세포가 존재하면 수축반응을, 내피세포가 제거되면 이완반응이 나타났다. 이 수축반응은 조사시간의 길이($10{\sim}320$초)에 비례하여 증가하였으나 이완반응은 그렇지 못하였다. 내피세포 존재표본에서 자외선의 수축반응은 phenylephrine농도의 증가($10^{-7}{\sim}10^{-5}M$) 그리고 $acetylcholine(10^{-6}M)$, $isoproterenol(10^{-7}M)$ 및 $nitroglycerin(3.5{\times}10^{-8} M)$의 추가투여시 크게 강화되었다. 그러나 $phentolamine(10^{-6}M)$ 또는 $LY83583(10^{-7},10^{-6}M)$의 추가투여시에는 자외선 수축반응이 억제 또는 이완반응으로 역전되었다. 내피세포 제거표본에서의 자외선 이완반응은 phenylephrine농도의 증가 그리고 isoproterenol, nitroglycerine, phentolamine 및 LY83583의 추가투여시 유의하게 감약되었다. 이상의 성적은 흰쥐 적출 흥부대동맥에서 자외선조사는 내피세포 존재유무에 따라 수축과 이완반응이 각각 나타나며, 수축반응은 자외선에 의한 EDRF 유리억제 또는 부분적으로 어떤 EDCF와도 관련이 있음을 시사하고 있다.