• Biomolecules & Therapeutics
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• v.8 no.1
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• pp.53-63
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• 2000

This study was performed to elucited the mechanisms of the antidiuretic action by SKP-450, a $K^+$ channel opener, given into the vein, and of the diuretic action observed only in the ipsilateral kidney, when given into a renal artery, in dog. The antidiuretic action of SKP-450 was not affected by renal denervation or pretreatment with glibenclamide, a ATP-dependent $K^+$ channel blocker. The diuretic action of SKP-450 was inhibited by renal denervation or pretreatment with glibenclamide. SKP-450 given into carotid artery had little effect on renal function. These results suggest that the antidiuretic action of SKP-450 given into the vein is caused by some endogenous substances probably not related to $K^+$ channel, whereas the diuretic action of SKP-450 observed only in ipsilateral kidney, when given into a renal artery, is provoked through $K^+$ channel related to renal nerves.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.160-160
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• 1993

목적: Guinea pig heart의 ATP sensitive $K^{＋}$ channel xenopus oocyte에 발현시켜 연구하고져 본 실험을 행하였다. 실험방법: 기니픽 심장으로부터 ,RNA를 분리하여 50ng/$\mu$l의 농도로 50nl를 xenopusdp 주입하였다. Xenpus oocyte에서 conventional electrode를 이용 막전휘를 측정하였고, pH selective 미세전극으로 세포내 pH를 측정하였다. 막전위에 미치는 potassium channel opener, blocker, KCN의 작용을 관찰하였다. 결과: 기니픽 심장 mRNA를 주입하거나 주입하지 않은 xenopus oocyte에서 $K^{＋}$channel opener인 cromakalin, RP49356등은 과분극을 일으키지 못하였다. 그러나 세포내 ATP 감소제인 KCN은 농도 의존적으로 과분극을 일으켰으나 ,glibenclamide에 의해 차단되는 않았다. mRNA를 주입한 oocyte에서 Na-H 자극제인 NH$_4$Cl은 pH 변동을 일으켜 NA-H exchange를 expression 시켰다. 결론: Xenopus oocyte는 cromakalin등에 의해 open되는 $K^{＋}$channel 은 없었고, 기니픽 심근의 ATP sensitive $K^{＋}$channel로 expression 되지 않았으나 Na-H exchange 는 expression 됨을 알 수 있었다. KCN으로 open 되는 $K^{＋}$channel이 있었으나 glibenclamide에는 차단되지 않는 channel이였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.96-96
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• 2001

This study was attempted to investigate the effect of cromakalim(CRK). $K^{-}$ channel opener, and glibenclamide(GLY), $K^{-}$ channel blocker, on intestinal function of rabbit. CRK supressed the tension and spontaneous movement of intestinal strips. Such CRK strengthened the tension and spontaneous movement of strips potentiated by acetylcholine, whereas more attenuated those weakened by dopamine. GLY augmented the tension, did not affect to the spontaneous movement of strips. GLY inhibited the acetylcholine-potentiated responses of tension and spontaneous movements in intestinal strips. GLY blocked the weakened responses of tension, while did not affect to the dopamine-weakened responses of spontaneous movements in intestinal strips. The present studies suggest that $K^{-}$ channel opening suppresses intestinal movements, whereas it's blockade enhances intestinal movements in rabbit.abbit.

• Biomolecules & Therapeutics
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• v.9 no.4
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• pp.237-243
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• 2001

This study was attempted to investigate the effects of cromakalim (CRK), $K^{+}$ channel opener, and glibenclamide (GLY), $K^{+}$ channel blocker, on intestinal function of rabbit. CRK supressed the tension and spontaneous movement of intestinal strips. CRK enhanced the tension and spontaneous movement of strips induced by acetylcholine. Also the inhibiting effect of dopamine was potentiated by CRK. GLY augmented the tension, but did not affect the spontaneous movement of strips. GLY inhibited tension and spontaneous movements in intestinal strips induced by acetylcholine, GLY blocked the dopamine-induced attenuation of tension, but not the decrease of spontaneous movements in intestinal strips. The present studies suggest that $K^{+}$ channel opening suppresses intestinal movements, whereas it's blockade enhances intestinal movements in rabbit.abbit.

• Biomolecules & Therapeutics
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• v.9 no.2
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• pp.96-103
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• 2001

These studies were investigated about influence of SKP 450, a $K^{+}$ channel opener, on the pressor actions induced by norepinephrine, angiotensin II and carotid artery occlusion in rats. Before these studies, effect of SKP 450 itself on blood pressure was examinated. SKP 450 produced the depressor action in proportionaly to dose of 0.3, 1.0 and 3.0 $\mu$g/kg given intravenously and this depressor action was weakened by pretreatment of glibenclamide, a $K^{+}$ channel blocker. The pressor action induced by norepinephrine, an alpha-adrenergic agonist, was blocked 1 hr after administation of SKP 450 in a dose of 3.0 $\mu\textrm{g}$/kg, i.v. and directly after in a dose of 6.0 $\mu\textrm{g}$/kg, i.v.. The pressor action induced by angiotensin II was blocked immediatly after treatment of SKP 450 in a dose of 3.0 $\mu\textrm{g}$/kg, i.v.. The pressor action caused by carotid artery occlusion was not affected by SKP 450 of 3.0 $\mu\textrm{g}$/kg, i.v., whereas markedly blocked by SKP 450 of 6.0 $\mu\textrm{g}$/㎦, i.v.. The potentiated-pressor actions of norepinephrine and angiotensin II by pretreatment of chlorisondamine, a autonomic ganglionic blocking agent, were also blocked by administration of SKP 450 in a dose of 6.0 $\mu\textrm{g}$/kg, i.v.. The weakened-pressor action of carotid artery occlusion by pretreatment of chlorisondamine was more weakened by SKP 450 6.0 $\mu\textrm{g}$/kg, i.v.. The results suggest that hyperpolarization formed through $K^{+}$ channel opening in cell membrane inhibits the pressor action induced norepinephrine ; angiotensin II ; and carotid artery occlusion.usion.

• YAKHAK HOEJI
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• v.43 no.5
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• pp.674-681
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• 1999

This study was performed to investigate the effects of renal denervation and cromakalim, a K+ Channel opener, on central diuretic action of glibenclamide, an ATP-dependent K+ Channel blocker, in dog. Diuretic action of glibenclamide administered into the vein was weakened markedly by renal denervation and pretreatment of of cromakalim. Above results suggest that central diuretic action of glibenclamide is mediated by renal nerves and K+ Channel localized in kidney.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.159-159
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• 1993

개의 관상동맥평활근세포를 이용하여 $K^{＋}$channel openers인 cromakalim과 pinacidil의 이완반응을 관찰하고, 이러한 이완반응의 세포내 기전에 대하여 검토하고자 하였다. Collagenase로 소화시켜 구한 평활근 세포들은 frypan blue 배출 검사 및 전자현미경학적으로 검사시 건전하고 생존해 있었다. 분산평활근세포들은 phenylephrine(PE)의 용량에 의존하여 수축하였고, EC$_{50}$는 2.3$\times$$10^{－12}$M이었다. PE에 의한 수축반응은 $K^{＋}$channel openers인 cromakalim 및 pinacidil의 용량에 의존하여 억제되었고 이때의 EC$_{50}$치는 각각 1,2$\times$$10^{－10}$M 및 6.B$\times$$10^{－10}$M이었다. 비교실험으로서 근절편의 장력을 측정하여 수축을 검정한 실험에서는 cromakalim의 이완반응의 ECEC$_{50}$치는 1.94$\times$$10^{－7}$ M로 근세포실험에 비하여 감수성이 훨씬 약하였다.훨씬 약하였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.44-44
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• 1992

최근 $K^{＋}$ channel openers인 cromakalim과 Pinacidil이 새로운 종류의 혈관확장제로서 항고혈압 치료제로 소개되었다. 그러나 이들 약물의 이완 효과와 새포내 작용기전은 분명치 않다. 따라서 본 연구에서는 개의 관상 동맥에서 얻은 평활근 세포에서 $K^{＋}$ channel openers에 의한 이완의 세포내 기전을 규명하고자 시도하였다 혈관 평할근 세포(dispersed smooth muscle cells)를 collagenase를 이용한 효소소화(enzymatic digestion)에 의해 분리하고, saponin을 이용하여 permeabilize되게 하였다. frypan blue exclusion과 전자 현미경적 관찰에 의하여 세포의 viability를 확인하였다. Dispersed intact cells은 phenylephrine (PE)에 의하여 용량의존 수축반응을 보였고 ED$_{50}$는 2.3 $\times$ $10^{-12}$ M이었다. 이러한 PE에 의한 수축반응은 cromakalim과 pinacidil (ED$_{50}$, 1.2 $\times$ $10^{-12}$ M)의 용량에 의존하여 억제되었다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.36-36
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• 1992

기니픽심장에서 유두근을 적출하여 valve 쪽은 silver wire에 연결하여 수축력을 측정하고 mural end는 sylgard floor에 pin으로 고정하여 1Hz로 자극하였다. 이때 사용된 영양액은 Tyrode Ringer로 bath내 은도는 36$^{\circ}C$이고 97% 0$_2$, 3% $CO_2$로 포화시켜 사용하였다. 수축력이 일정해진 후 막전위는 conventional electrode를 이용해서 기록하고, 세포내 $Na^{＋}$ 이온 활성도( $a_{Na}$ $^{i}$ )는 $Na^{＋}$ 선택적 전극을 이용해서 기록하였다. 적출 기니픽 심근에서 pinacidil, cromakalim, RP49356 둥의 $K^{＋}$ channel opener는 활동전위 기간(APD)과 수축력 감소을 일으켰고, pinacidil과 cromakalim에 의한 APD 감소는 glibenclamide (10 $\mu$M)에 의해 거의 억제되었다. Pinacidil, RP49356 및 cromakalim에 의한 수축력 감소시 세포내 $Na^{＋}$ 이온농도( $a_{Na}$ $^{i}$ )의 감소가 나타났으며 glibenclamide(10 $\mu$M)에 의한 APD의 감소는 거의 차단되었으나 $a_{Na}$ $^{i}$ 감소는 일부 나타났으며 이때 수축력의 감소도 나타났다.

• Biomolecules & Therapeutics
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• v.8 no.1
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• pp.44-52
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• 2000

SKP-450 which is $K^{+}$ channel opener, When given into duodenum, exhibited the decline of urine flow accompanied with the decrease of glomerular filtration rates (GFR), renal plasma flow (RPF), N $a^{+}$ and $K^{+}$ excreated in the urine ( $E_{Na}$ , $E_{K}$) and the increase of $K^{+}$N $a^{+}$ratios, and then appeared the significant fall of mean arterial pressure (MAP) and unchanged of reabsorption rates of N $a^{+}$, $K^{+}$ in renal tubules ( $R_{Na}$ , $R_{K}$). SKP- 450 injected into the vein elicited the decline of urine flow along with the reduction of $E_{Na}$ , $E_{K}$, and the increase of $R_{Na}$ , $R_{K}$ and $K^{+}$M $a^{+}$ ratios. SKP-450 administered into a renal artery produced diuretic action along with the increase of $E_{Na}$ , $E_{K}$ and the decrease of $R_{Na}$ , $R_{K}$ in experimental kidney, whereas produced the same aspect to intravenous SKP-450 in the control kidney. Above results suggest that SKP-450 possess both diuretic action in the kidney and central antidiuretic action in dog.tic action in dog.tion in dog.