Synthesis of Higenamine and its Cardiovascular Effects in Rabbit: Evidence for ${\beta}-Adrenoceptor$ agonist

장기철,임정규,박찬웅,Chang, Ki-Churl,Lim, Jung-Kyoo,Park, Chan-Woong The Korean Society of Pharmacology 1986 대한약리학잡지 Vol.22 No.2

최근에 미나라아제비과 (Ranunculaceae)에 속하는 부자(Aconiti tuber)로부터 강심작용을 나타내는 성분을 분리하여 Higenamine이라 명명하였고 그 작용기전을 밝히려는 시도가 활발히 진행되고 있다. 그러나 생약제로 부터 얻을 수 있는 Higenamine은 극히 미량이고 그 과정 또한 복잡하다. 따라서 본 연구에서는 유효성분을 대량 얻기 위한 방법으로서 전합성(total Synthesis)을 시도하였으며 IR, UV, NMR 및 elemental 분석등을 통하여 합성된 물질을 확인하였으며 가토에 대하여 in vivo에서 혈압, 심박동수, 호흡 및 말초저항에 미치는 영향과 아울러 in vitro에서 심근수축 증강작용(positive inotropic action) 및 심박속도 증강작용(positivechronotropic action)을 관찰 분석하여 다음과 같은 결론을 얻었다. 1) Higenamine은 $1-10\;{\mu}g/kg/min$ 정맥주사시 수축기 및 이완기혈압 모두를 용량 의존적으로 하강시켰고 후자가 전자보다 더욱 현저하였으며 호흡은 촉진되었고 말초 혈류량은 증가되었으나 심박동수는 영향이 없었다. 2) 혈압에 대한 Higenamine의 작용은 propranolol 전처치에 의하여 억제되었다. 3) Higenamine의 catechol핵과 커다란 아미노기는 베타 수용체기 대하여 전자는 활성을 후자는 친화력과 관계있을 것으로 추정하였다. 이상의 결과 Higenamine은 adrenergic ${\beta}$-수용체에 작용하여 그 작용을 발휘하는 것으로 사료 되었다. Higenamine, dl-1-( 4-hydroxybenzyl)-6, 7-dihydroxy-1 ,2, 3 ,4-tetrahydroisoquinoline has been synthesized and evaluated for hemodynamic actions using rabbits under pentobarbital anesthesia. Concentration-related fall of mean blood pressure was observed, where diastolic blood presure was significantly lowered at 10 ug/kg/min or above (p<.05), while the systolic blood pressure was slightly increased or unaffected, thereby, causing increment of pulse pressure. No significant change was occured in heart rate, however, carotid artery blood flow was significantly (p<.05) increased. These actions were inhibited with pretreatment of 0.3 mg/kg of propranolol, beta-adrenoceptor antagonist, 5 minutes before infusion of higenamine indicating that higenamine compete with propranolol for the so-called beta adrenergic receptor. As comparison, the same procedure was applied to isoproterenol as well, where typical antagonism of propranolol against isoproterenol was shown. From these findings the vasodilating and diastolic blood pressure lowing effects could be explained in terms of cardiac beta stimulating action, however, dopamine receptor activation could not be excluded because no significant changes observed in chronotropism.

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.

The Effect of Higenamine upon the Interval-Strength Relationship in Isolated Rabbit Heart

장기철,Chang, Ki-Churl The Korean Society of Pharmacology 1983 대한약리학잡지 Vol.19 No.2

현재 사용되고 있는 강심제로는 디지탈리스 배당체가 유일한 약물이지란 그 안전역이 대단히 좁아서 보다 안전한 강심제의 개발이 요구되고 있다. 최근 강심작용이 현저할 뿐 아니라 안전역이 비교적 넓을 것으로 인정되는 higenamine이 개발되어 그 작용기전을 밝히려는 시도가 많이 있었다. 본 연구에서는 higenamine의 강심작용 기전을 규명하기 위한 연구의 일환으로 수축빈도-수축력 상관관계(interval-strength relationship)에 있어서 1) Rested-state수축력 2) Positive inotropic effect of activation(PIEA) 3) Negative inotropic effect of activation(NIEA)에 대한 higenamine의 영향을 $Ca^{++}$및 epinephrine과 비교 분석하였다. 실험결과 칼슘은 PIEA를 증가시키기 보다는 오히려 NIEA의 소멸을 촉진함으로써 강심작용을 나타내며 epinephrine 및 higenamine은 PIEA를 증가시키고 NIEA에는 거의 영향을 미치지 않았다. The effect of higenamine upon the interval-strength relationship was kinetically analyzed, and compared them with epinephrine and calcium ion. The followings are result obtained : 1) Polyphasic patterns were seen by all agents applied on the interval-force curve of rabbit atrial muscle. 2) Higenamine, unlike calcium ion, increased the amount of PIEA produced per beat dose-dependently and scarcely affected the disappearance of NIEA. 3) Higenamine appeared to similar pattern with epinephrine in augmenting the PIEA, not affecting the NIEA. 4) Calcium ion slightly influenced the PIEA, rather hastened the disappearance of NIEA. From these result the positive inotropic action of higenamine was attributed solely to increment of PIEA.

Possible Role of Nitric Oxide in Prevention of Atherosclerosis: Photo-induced adequate nitric oxide (PIANO)-mediated relaxation involves cyclic GMP increment

장기철,정원석,박병욱,이승엽,고학준,Chang, Ki-Churl,Chong, Won-Seog,Park, Byung-Wook,Lee, Seung-Youb,Ko, Hak-Joon The Korean Society of Pharmacology 1994 대한약리학잡지 Vol.30 No.3

본 연구의 목적은 광 유도에 의한 nitric oxide (PIANO)유리가 혈관이완에 대해 cyclic GMP (cGMP)가 관여하는 지의 여부와 아울러 ${\alpha}$-수용체를 통한 수축에 PIANO가 어떻게 작용하는 지를 파악하고자 하였다. In vitro 실험에서 흰쥐의 대동맥을 준 최고농도의 phenylephrine (PE)으로 수축시킨 후 nitric oxide 생성을 변화시키는 약물이나 광민감성 (photosensitizing) 약물에 대한 반응을 등장력 변화로 기록하였다. PIANO에 의한 혈관이완은 광노출 강도와 기간 및 광민감성 약물농도에 비례하여 증가하였고 cGMP의 증가를 수반하였다. PE에 의해 증대되는 phosphatidylinositide(PI) 전환은 PIANO에 의해 억제되었다. 이상의 결과는 cGMP의 증가로 인해 PIANO에 의한 혈관이완이 일어나며 ${\alpha}$-아드레날성 수용체 자극에 의한 PI 전환의 억제현상은 cGMP 증가의 결과로 생각할 수 있다. 결론적으로 PIANO에 의한 혈관이완은 cGMP의 증가로 인함을 확인할 수 있었다. Our purpose was to know whether photo-induced adequate nitric oxide (PIANO)-mediated relaxation of rat aorta is involved in cyclic GMP increment as well as inhibition of phosphatidylinositide hydrolysis due to phenylephrine (PE). Isometric tension was measured in vitro in response to either agents that modulate NO production or release NO by photolysis of photosensitizing agents in rat aorta that had been contracted with PE submaximally. PIANO-mediated relaxation was accompanied by increment of cyclic GMP, which was dependent on the intensity and duration of light exposure and concentration of photosensitizers. Phosphatidylinositide (PI) turnover augmented by PE was significantly inhibited by PIANO. These findings indiate that cGMP increment is responsible for PIANO-mediated relaxation and which may account for the inhibition of PI turnover due to ${\alpha}-adrenergic$ receptor stimulation.

Calcium Channel Blocking and Phosphodiesterase Inhibitory Action of GS386, a Dihydroisoquinoline Derivative, in Isolated Rat Trachea

장기철,이회영,강영진,구의본,Chang, Ki-Churl,Lee, Hoi-Young,Kang, Young-Jin,Koo, Eui-Bon The Korean Society of Pharmacology 1996 대한약리학잡지 Vol.32 No.3

최근 본 연구실에서는 GS 386인 1-(4'-methoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline이 적출된 토끼의 심방세포에서 $Ca^{++}$ 채널의 운동성 변화없이 $Ca^{++}$ 채널이 열릴 가능성을 줄임으로써 $Ca^{++}$ 전류의 증폭을 억제한다고 보고하였다. 이번 연구에서는 적출된 쥐의 기관지를 사용하여 GS 386의 작용기전에 대해 연구하였다. GS386은 carbachol $(0.3{\mu}M)$과 높은 농도의 $K^+$ (65.4mM)에 의해 수축된 쥐의 기관지를 용량-의존적으로 이완시켰으며 이때 $IC_{50}$는 5.24와 $5.67\;{\mu}M$이었다. verapamil은 carbachol에 의한 수축시 보다 높은 농도의 $K^+$에 의해 수축된 조직에 더욱 효과적으로 억제하였다. $Ca^{++}$이 없는 상태에서 $Ca^{++}$에 의한 수축은 GS386에 의해 억제되었다. 더욱이 높은 농도의 GS386$(100\;{\mu}M)$은 verapamil과는 다르게 carbachol뿐만 아니라 caffeine에 의한 위상성 수축을 억제 시키므로 GS386은 세포질내로 들어가 sarcoplasmic retuculum과 같은 근육 내부에 2차적인 영향을 나타내었다. 더군다나GS386은 verapamil에 의해 영향을 받지않는 (verapamil-insensitive component)이완을 보였고 쥐 기관지의 평활근에서 cAMP의 양을 증가 시켰다. 이러한 결과는 GS386의 작용기전이 $Ca^{++}$ 길항적인 작용 뿐만 아니라 posphodiesterase억제작용에 기인한다는 사실을 제시한다. Recently we reported that GS 386, 1-(4'-methoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline, inhibited amplitude of the $Ca^{2+}$ current by reducing the probability of $Ca^{2+}$ channel opening without changing channel kinetics in isolated rabbit atrial myocyte. In the present study, further investigation of the mechanism of action of GS 386 was performed using isolated rat trachealis. GS 386 concentration-dependently relaxed rat trachealis contracted by carbachol $(0.3{\mu}M)$ and high $K^+$(65.4 mM) with $IC_{50}$ 5.24 and 5.67 ${\mu}M$, respectively. Verapamil inhibited more effectively the high $K^+-contracted$ tissues than those with carbachol in the rat trachealis muscle. In $Ca^{2+}-free$ media, $Ca^{2+}-induced$ contraction was inhibited by GS 386. Furthermore, high concentration of GS 386 $(100{\mu}M)$ but not verapamil, attenuated a phasic contraction induced not only by carbachol but also caffeine, indicating that GS386 can enter into the cytoplasm where it may exert secondary actions on internal sites of the muscle, such as sarcoplasmic reticulum. Moreover, GS 386 showed verapamil-resistant component of relaxation and increased cAMP levels in rat trachal smooth muscle. These results suggest that the mechanism of action of GS 386 attributes to not only $Ca^{2+}$ antagonistic action but also weak phosphodiesterase inhibitory action.

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.

동맥경화 예방과 치료를 위한 연구시도: Nitric Oxide의 역활 -광 유도 nitric oxide(PIANO)의 혈관이완에 따른 cyclic GMP의 증가

장기철(Ki Churl Chang),정원석(Won Seog Chong),박병욱(Byung Wook Park),이승엽(Seung Youb Lee),고학준(Hak Joon Ko) 대한약리학회 1994 대한약리학잡지 Vol.30 No.3

본 연구의 목적은 광 유도에 의한 nitric oxide (PIANO)유리가 혈관이완에 대해 cyclic GMP (cGMP)가 관여하는 지의 여부와 아울러 α-수용체를 통한 수축에 PIANO가 어떻게 작용하는 지를 파악하고자 하였다. In vitro 실험에서 흰쥐의 대동맥을 준 최고농도의 phenylephrine (PE)으로 수축시킨 후 nitric oxide 생성을 변화시키는 약물이나 광민감성 (photosensitizing) 약물에 대한 반응을 등장력 변화로 기록하였다. PIANO에 의한 혈관이완은 광노출 강도와 기간 및 광민감성 약물농도에 비례하여 증가하였고 cGMP의 증가를 수반하였다. PE에 의해 증대되는 phosphatidylinositide(PI) 전환은 PIANO에 의해 억제되었다. 이상의 결과는 cGMP의 증가로 인해 PIANO에 의한 혈관이완이 일어나며 α-아드레날성 수용체 자극에 의한 PI 전환의 억제현상은 cGMP 증가의 결과로 생각할 수 있다. 결론적으로 PIANO에 의한 혈관이완은 cGMP의 증가로 인함을 확인할 수 있었다. Our purpose was to know whether photo-induced adequate nitric oxide (PIANO)-mediated relaxation of rat aorta is involved in cyclic GMP increment as well as inhibition of phosphatidylinositide hydrolysis due to phenylephrine (PE). Isometric tension was measured in vitro in response to either agents that modulate NO production or release NO by photolysis of photosensitizing agents in rat aorta that had been contracted with PE submaximally. PIANO-mediated relaxation was accompanied by increment of cyclic GMP, which was dependent on the intensity and duration of light exposure and concentration of photosensitizers. Phosphatidylinositide (PI) turnover augmented by PE was significantly inhibited by PIANO. These findings indiate that cGMP increment is responsible for PIANO-mediated relaxation and which may account for the inhibition of PI turnover due to α-adrenergic receptor stimulation.

관상동맥이완과 혈소판응집에 대한 GS283 과 GS386 의 약리작용기전에 관한 연구

장기철(Ki Churl Chang),이회영(Hoi Young Lee),이균우(Goun Woo Lee),구의본(Eui Bon Koo),강영진(Young Jin Kang),이영수(Young Soo Lee) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.3

Trimetoquinol (TMQ) and its analogs are known to have thromboxane A₂ antagonistic action. We also reported that GS389, chemically similar to TMQ, has competitive antagonistic action in rat aorta and human platelets. In the present study, we investigated the pharmacological characteristics of GS283 and GS386, analogs of GS389, using vascular smooth muscle, human platelets and rat brain homogenates. In isolated pig coronary artery (PCA), both of GS283 and GS386 relaxed U46619-contracted rings in concentration dependent manner. Pretreatment with several concentrations of GS283 and GS386 shifted the dose-response curves to the right, and reduced of maximum contration dose-dependently. Furthermore, GS283 and GS386 strongly inhibited Ca^(2+)-induced contraction in the PCA. In human platelets, U46619- and A23187-induced platelet aggregation was inhibited by GS283 and GS386, concentration-dependently. Anti-platelet aggregation was related to the compound`s ability to inhibit ATP release at each stimulation. In rat brain homogenates, receptor-binding assay resulted that both GS283 and GS386 have a relative affinity to α-adrenergic receptor. Taken together, we concluded that the mechamism of action of GS283 and GS386 is not related with in TXA₂ receptor but concerned with calcium antagonistic action and α-blocking action.

Higenamine의 합성 및 가토의 심혈관계에 미치는 영향 : 베타-아드레날린성 효능 약물

장기철(Ki-Churl Chang),임정규(Jung-Kyoo Lim),박찬웅(Chan-Woong Park) 대한약리학회 1986 대한약리학잡지 Vol.22 No.2

최근에 미나라아제비과 (Ranunculaceae)에 속하는 부자(Aconiti tuber)로부터 강심작용을 나타내는 성분을 분리하여 Higenamine이라 명명하였고 그 작용기전을 밝히려는 시도가 활발히 진행되고 있다. 그러나 생약제로 부터 얻을 수 있는 Higenamine은 극히 미량이고 그 과정 또한 복잡하다. 따라서 본 연구에서는 유효성분을 대량 얻기 위한 방법으로서 전합성(total Synthesis)을 시도하였으며 IR, UV, NMR 및 elemental 분석등을 통하여 합성된 물질을 확인하였으며 가토에 대하여 in vivo에서 혈압, 심박동수, 호흡 및 말초저항에 미치는 영향과 아울러 in vitro에서 심근수축 증강작용(positive inotropic action) 및 심박속도 증강작용(positivechronotropic action)을 관찰 분석하여 다음과 같은 결론을 얻었다. 1) Higenamine은 1-10μg/kg/min 정맥주사시 수축기 및 이완기혈압 모두를 용량 의존적으로 하강시켰고 후자가 전자보다 더욱 현저하였으며 호흡은 촉진되었고 말초 혈류량은 증가되었으나 심박동수는 영향이 없었다. 2) 혈압에 대한 Higenamine의 작용은 propranolol 전처치에 의하여 억제되었다. 3) Higenamine의 catechol핵과 커다란 아미노기는 베타 수용체기 대하여 전자는 활성을 후자는 친화력과 관계있을 것으로 추정하였다. 이상의 결과 Higenamine은 adrenergic β-수용체에 작용하여 그 작용을 발휘하는 것으로 사료 되었다. Higenamine, dl-1-( 4-hydroxybenzyl)-6, 7-dihydroxy-1 ,2, 3 ,4-tetrahydroisoquinoline has been synthesized and evaluated for hemodynamic actions using rabbits under pentobarbital anesthesia. Concentration-related fall of mean blood pressure was observed, where diastolic blood presure was significantly lowered at 10 ug/kg/min or above (p<.05), while the systolic blood pressure was slightly increased or unaffected, thereby, causing increment of pulse pressure. No significant change was occured in heart rate, however, carotid artery blood flow was significantly (p<.05) increased. These actions were inhibited with pretreatment of 0.3 mg/kg of propranolol, beta-adrenoceptor antagonist, 5 minutes before infusion of higenamine indicating that higenamine compete with propranolol for the so-called beta adrenergic receptor. As comparison, the same procedure was applied to isoproterenol as well, where typical antagonism of propranolol against isoproterenol was shown. From these findings the vasodilating and diastolic blood pressure lowing effects could be explained in terms of cardiac beta stimulating action, however, dopamine receptor activation could not be excluded because no significant changes observed in chronotropism.

가토의 근위와 원위대장 평활근의 운동성 비교

김주헌,장기철,윤효인,Kim, Joo-heon,Chang, Ki-churl,Yun, Hyo-in 대한수의학회 1987 大韓獸醫學會誌 Vol.27 No.1

To validate the comparision of proximal and distal large intestinal motility, the amplitude and frequency of spontaneous motility, the effect of acetylcholine, the effect of atropine on the response of acetylcholine, the effect of histamine and the effect of pyrilamine and cimetidine on the response of histamine were investigated in rabbit. The results were summarized as follows: 1. The amplitude of spontaneous motility was more powerful on the proximal large intestine than that of the distal large intestine, but the frequency of spontaneous motility was similar on the both proximal and distal large intestine in rabbit. 2. Acetylcholine caused the contraction of proximal and distal large intestine, and the contractile response were increased between the concentration of acetylcholne $10^{-9}$ and $5{\times}10^{-6}M$ and $10^{-7}$ and $10^{-4}M$ on the proximal and distal large intestine, respectively, with dose-dependent manner in rabbit. 3. The contractile response induced by acetylcholine was completely blocked by the post-treatment with cholinergic receptor blocker, atropine $10^{-6}M$. 4. Histamine caused the contraction of proximal and distal large intestine and the contractile response were increased between the concentration of histamine $10^{-9}$ and $5{\times}10^{-5}M$ and $10^{-5}$ and $10^{-3}M$ on the proximal and distal large intestine, respectively, with dose-depend ent manner in rabbit. 5. The contractile response induced by histamine was completely blocked by the pretreatment with $H_1$-receptor blocker, pyrilamine $10^{-6}M$, but not blocked by the pretreatment with $H_2$-receptor blocker, cimetidine $10^{-6}M$.