Veterinary Education in Japan

Hideaki Karaki 대한수의학회 2001 대한수의학회 학술대회발표집 Vol.2001 No.-

Novel Macrolide Actin-inhibitors Isolated from Sea Sponges

Karaki, Hideaki,Ozaki, Hiroshi The Korean Society of Toxicology Korea Environment 2001 Toxicological Research Vol.17 No.-

Several marine toxins with macrolide structure have been found to act on actin. One of these toxins is mycalolide B isolated from the genus Mycale. This compound belongs to macrolide antibiotics and consists of tris-oxazole with strong cytotoxic activity ($IC_{50}$: 10-50 nM for growth of L1210 murine leukemia cells). This compound was found to be an actin-depolymerizing agent with the mode of action distinct from that of the known actin inhibitor, cytochalasin D. Tolytoxin, a macrolide isolated from cyano-bacteria with similar chemical structure to mycalolide B, seems to have similar effect. Another macrolide compound, aplyronine A, showed the effects similar to those of mycalolide B. Although bistheonellide A, a dimeric macrolide, did not show a severing effect, it de polymerized F-actin and sequestered G-actin by forming 1 : 2 complex with G-actins. Swinholide A has a structure and effects similar to those of bistheonel-lide A. In conclusion, mycalolide B, tolytoxin, aplyronine A, bistheonellide A and swinholide A are the members of "actin de polymerizing macrolide" the mechanism of which is different from that of cytochalasin D.halasin D.

세계수의학교육의 수준과 일본에서의 수의학교육 개선

당목영명,Karaki Hideaki 대한수의사회 2000 대한수의사회지 Vol.36 No.5

자궁평활근의 Carbachol 및 Oxytocin 수축에 있어서의 세포내 $Ca^{2+}$ 동원

김보경,정동수,김윤선,이윤호,용준환,이원창,이상목,Kim, Bo-Kyung,Chung, Dong-Su,Kim, Yoon-Sun,Lee, Yoon-Ho,Yong, Jun-Hwan,Lee, Won-Chang,Ozaki, Hiroshi,Karaki, Hideaki,Lee, Sang-Mog 대한약리학회 1996 대한약리학잡지 Vol.32 No.2

The properties of cytosolic $Ca^{2+}$ level$([Ca^{2+}]_i)$ movement of high KCl, carbachol and oxytocin were examined with myometrium isolated from non-pregnant rat(estrus cycle). High concentration of KCl$({\leq}23.3mM)$ induced rhythmic increases in $[Ca^{2+}]_i$ and muscle contraction. However, sustained $[Ca^{2+}]_i$ and contracion were obtained at higher KCl concentration $({\geq}30.3mM)$ The rhythmic and sustained contraction closely associated with changes in $[Ca^{2+}]_i$ induced by high KCl. Carbachol $(3{\sim}30{\mu}M$ generated rhythmic increases with tonic component in $[Ca^{2+}]_i$ and muscle contraction. Myometrial contraction stimulated by carbachol was also closely correlated with change in $[Ca^{2+}]_i$. And the $[Ca^{2+}]_i/contraction$ relationships were similar when muscle strips were stimulated by high KCl and carbachol. Maximal concentration of carbachol $(10{\mu}M)$ and oxytocin(100 nM) increased $[Ca^{2+}]_i$ and contraction which were slightly greater than that of high KCl in non-pregnant myometrium, respectively. However, the $[Ca^{2+}]_i$ and contraction were strongly inhibited by verapamil $(10{\mu}M)$, a 1-type $Ca^{2+}$ channel blocker, as in the case of high KCl. Additionally, although carbachol further increased $[Ca^{2+}]_i$ and contraction induced by high KCl, these changes also strongly inhibited by application of verapamil. These results suggest that uterotonic agents, carbachol and oxytocin, induced contraction by increase in $[Ca^{2+}]_i$ through $Ca^{2+}$ influx than by a regulation of $Ca^{2+}-sensitization$ in non-pregnant myometrium.

자궁평활근의 Carbachol 및 Oxytocin 수축에 있어서의 세포내 Ca²⁺ 동원

김보경(Bo-Kyung Kim),정동수(Dong-Su Chung),김윤선(Yoon-Sun Kim),이윤호(Yoon-Ho Lee),용준환(Jun-Hwan Yong),이원창(Won-Chang Lee),Hiroshi Ozaki,Hideaki Karaki,이상목(Sang-Mog Lee) 대한약리학회 1996 대한약리학잡지 Vol.32 No.2

The properties of cytosolic Ca²⁺ level([Ca²⁺]_i) movement of high KCl, carbachol and oxytocin were examined with myometrium isolated from non-pregnant rat(estrus cycle). High concentration of KCl≤23.3mM) induced rhythmic increases in [Ca²⁺]_i and muscle contraction. However, sustained [Ca²⁺]_i and contracion were obtained at higher KCl concentration (≥30.3mM) The rhythmic and sustained contraction closely associated with changes in [Ca²⁺]_i induced by high KCl. Carbachol (3 ~ 30μM generated rhythmic increases with tonic component in [Ca²⁺]_i and muscle contraction. Myometrial contraction stimulated by carbachol was also closely correlated with change in [Ca²⁺]_i. And the [Ca²⁺]_i/contraction relationships were similar when muscle strips were stimulated by high KCl and carbachol. Maximal concentration of carbachol (10μM) and oxytocin(100 nM) increased [Ca²⁺]_i and contraction which were slightly greater than that of high KCl in non-pregnant myometrium, respectively. However, the [Ca²⁺]_i and contraction were strongly inhibited by verapamil (10μM), a 1-type Ca²⁺ channel blocker, as in the case of high KCl. Additionally, although carbachol further increased [Ca²⁺]_i and contraction induced by high KCl, these changes also strongly inhibited by application of verapamil. These results suggest that uterotonic agents, carbachol and oxytocin, induced contraction by increase in [Ca²⁺]_i through Ca²⁺ influx than by a regulation of Ca²⁺-sensitization in non-pregnant myometrium.

GS354 and GS389: New Type of Calcium Channel Blockers

장기철,손동렬,정원석,정수연,이영수,김시환,노홍기,서정서,다까자와,가라끼,Chang, Ki-Churl,Sohn, Dong-Ryul,Chong, Won-Seog,Chung, Soo-Youn,Lee, Young-Soo,Kim, Si-Hwan,Noh, Hong-Kee,Suh, Joung-Seo,Takizawa, Satoko,Karaki, Hideaki The Korean Society of Pharmacology 1991 대한약리학잡지 Vol.27 No.1

GS354와 GS389의 세포내 칼슘{$[Ca^{2+}]_{1}:$ Fura-2의 형광으로 측정}과 근장력 변화에 대하여 백서의 흉부동맥을 사용하여 검토하였다. GS354와 GS389 모두 고농도의 포타슘과 노어에피네프린에 의한 수축을 억제시켰다. GS354의 헐관이완은 $[Ca^{2+}]_{1}$의 감소가 동반되었고 고농도의 포타슘에 의한 $[Ca^{2+}]_{1}$증가억제 현상도 칼슘통로 활성제인 Bay K8644에 의하여 길항되었다. 그러나 혈관이완 작용은 Bay K8644에 의해 억제 되지 않았다. 이러한 사실은 GS354는 칼슘통로를 차단하여 $[Ca^{2+}]_{1}$을 감소시키며 또한 수축기구에 대한 칼슘의 감수성을 낮추는 것을 암시하는 결과이다. 한편 GS389는 세포내 형광성을 증가시켰으나 이것은 Fura-2에 의한 형광이 아니라 내인성 피리딘 뉴클레오타이드에 의한 것으로서 나타났다. 이것은 미토콘드리아 기능을 억제하는 것을 의미하며 이러한 현상때문에 GS389에 대한 $[Ca^{2+}]_{1}$의 측정이 곤란하였으나 계속하여 Bay K8644를 첨가하여 본 결과 형광은 더욱 증가 되었으나 혈관이완은 역전되지 않았다. 이러한 사실은 GS389가 칼슘통로를 억제하며 아울러 수축기구에 대한 칼슘의 감수성을 낮추는 것을 암시하는 결과로 사료된다. The inhibitory effects of GS354 and GS389 on cytosolic $Ca^{2+}$ level ($[Ca^{2+}]_{1}$; measured with fura-2 fluorescence) and muscle tension in vascular smooth muscle of rat thoracic aorta were investigated. Both GS354 and GS389 inhibited the contractions induced by high $K^+$ or by norepinephrine. The vasodilator effect of GS354 was accompanied by a decrease in $[Ca^{2+}]_{1}$. The inhibitory effect on high $K^+-stimulated$ $[Ca^{2+}]_{1}$ was antagonized by a $Ca^{2+}$ channel activator, Bay K8644. However, the inhibitory effect on muscle tension was not antagonized by Bay K8644. These results suggest that GS354 inhibits $Ca^{2+}$ channels to decrease $[Ca^{2+}]_{1}$ and also decreases $Ca^{2+}$ sensitivity of contractile elements. The inhibitory effects of GS389 was accompanied by the increase in tissue fluorescence. This increment was not due to fura-2 fluorescence but to endogeneous pyridine nucleotides, suggesting that GS389 has an effect to inhibit mitochondrial function. Because of this interference, effects of GS389 on $[Ca^{2+}]_{1}$ was obscured. However, since sequential addition of Bay K8644 in the presence of GS389 further increased the fluorescence but not muscle tension, this compound seems to have the effects to inhibit $Ca^{2+}$ channels and to decrease $Ca^{2+}$ sensitivity of contractile elements.

GS354, GS389: 새로운 칼슘 길항제

장기철(Ki Churl Chang),손동렬(Dong-Ryul Sohn),정원석(Won Seog Chong),정수연(Soo Youn Chung),이영수(Young Soo Lee),김시환(Si Hwan Kim),노홍기(Hong Kee Noh),서정서(Joung Seo Suh),다까자와(Satoko Takizawa),가라끼(Hideaki Karaki) 대한약리학회 1991 대한약리학잡지 Vol.27 No.1

The inhibitory effects of GS354 and GS389 on cytosolic Ca²⁺ level ([Ca²⁺]₁; measured with fura-2 fluorescence) and muscle tension in vascular smooth muscle of rat thoracic aorta were investigated. Both GS354 and GS389 inhibited the contractions induced by high K⁺ or by norepinephrine. The vasodilator effect of GS354 was accompanied by a decrease in [Ca²⁺]₁. The inhibitory effect on high K⁺-stimulated [Ca²⁺]₁ was antagonized by a Ca²⁺ channel activator, Bay K8644. However, the inhibitory effect on muscle tension was not antagonized by Bay K8644. These results suggest that GS354 inhibits Ca²⁺ channels to decrease [Ca²⁺]₁ and also decreases Ca²⁺ sensitivity of contractile elements. The inhibitory effects of GS389 was accompanied by the increase in tissue fluorescence. This increment was not due to fura-2 fluorescence but to endogeneous pyridine nucleotides, suggesting that GS389 has an effect to inhibit mitochondrial function. Because of this interference, effects of GS389 on [Ca²⁺]₁ was obscured. However, since sequential addition of Bay K8644 in the presence of GS389 further increased the fluorescence but not muscle tension, this compound seems to have the effects to inhibit Ca²⁺ channels and to decrease Ca²⁺ sensitivity of contractile elements. GS354와 GS389의 세포내 칼슘{[Ca²⁺]₁: Fura-2의 형광으로 측정}과 근장력 변화에 대하여 백서의 흉부동맥을 사용하여 검토하였다. GS354와 GS389 모두 고농도의 포타슘과 노어에피네프린에 의한 수축을 억제시켰다. GS354의 헐관이완은 [Ca²⁺]₁의 감소가 동반되었고 고농도의 포타슘에 의한 [Ca²⁺]₁증가억제 현상도 칼슘통로 활성제인 Bay K8644에 의하여 길항되었다. 그러나 혈관이완 작용은 Bay K8644에 의해 억제 되지 않았다. 이러한 사실은 GS354는 칼슘통로를 차단하여 [Ca²⁺]₁을 감소시키며 또한 수축기구에 대한 칼슘의 감수성을 낮추는 것을 암시하는 결과이다. 한편 GS389는 세포내 형광성을 증가시켰으나 이것은 Fura-2에 의한 형광이 아니라 내인성 피리딘 뉴클레오타이드에 의한 것으로서 나타났다. 이것은 미토콘드리아 기능을 억제하는 것을 의미하며 이러한 현상때문에 GS389에 대한 [Ca²⁺]₁의 측정이 곤란하였으나 계속하여 Bay K8644를 첨가하여 본 결과 형광은 더욱 증가 되었으나 혈관이완은 역전되지 않았다. 이러한 사실은 GS389가 칼슘통로를 억제하며 아울러 수축기구에 대한 칼슘의 감수성을 낮추는 것을 암시하는 결과로 사료된다.