해명 회장 운동에 대한 아드레나린성 α-수용체에 관한 연구

고창만(Chang Mann Ko) 대한약리학회 1983 대한약리학잡지 Vol.19 No.1

Intestine is innervated by an interconnected plexus of both sympathetic and parasympathetic nerve fibers. Sympathetic influence causes inhibition of intestinal motility mediated by both α- and β-adrenergic receptors. The mechanism of intestinal relaxation by β-receptors has been extensively studied, but the function of α-receptors in intestinal motility is still unclear. Although it is suggested that catecholamine reduces acetylcholine release and this may play an important role in α-receptor mediated intestinal relaxation, there is no definite evidences about the mechanism and site of action of α-receptor mediated relaxation. In this experiment, therefore, the effect and site of action of α-receptor agonists were investigated in the guinea pig ileum using electrical field stimulation. The results are summarized as follows : 1) Electrical field stimulation elicited tonic contraction in isolated guinea pig ileum ana this contraction was completely inhibited by the pretreatment of tetrodotoxin or atropine. 2) Norepinephrine, epinephrine and dopamine inhibited the contraction induced by electrical field stimulation but methoxamine and phenylephrine had little effects. 3) Inhibitory effects of norepinephrine and dopamine was partially blocked by yohimbine and phentolamine pretreatment. But haloperidol and propranolol pretreatment cause no effects on the electrical field stimulation induced contraction. Inhibitory effect of dopamine was completely blocked by both haloperidol and yohimbine pretreatment. 4) Inhibitory effects of norepinephrine and dopamine were little affected by the pretreatment with hexamethonium. It is suggested that electrical field stimulation causes tonic contraction of guinea pig ileum by releasing acetylcholine from postganglionic fiber, and this release is blocked by presynaptic α-receptor activation.

The Pharmacological Studies on the Origin of Calcium ion in Myocardial Contraction

고창만,김경환,Ko, Chang-Mann,Kim, Kyung-Hwan The Korean Society of Pharmacology 1994 대한약리학잡지 Vol.30 No.1

Na-Ca 교환은 calcium 이온을, 세포 내외의 Na 이온 농도차에 의해서 형성되는 원동력의 방향에 따라, 세포내로(역방향 Na-Ca 교환), 혹은 세포밖으로(정방향 Na-Ca 교환) 이동시킨다. 그러므로 Na-Ca 교환은 심근 수축 운동의 조절 기전의 하나로 받아 들여지고 있다. 그러나, 세포내의 Na 이온 농도는 항상 세포외의 농도보다 낮으므로, 역방향 Na-Ca 교환의 존재와 아울러 이의 심근 수축에 있어서의 역할 가능성에 대해 많은 연구자들이 회의를 가지고 있는 것이 사실이다. 그러므로 본 연구는 흰쥐의 좌심방을 이용하여, 역방향 Na-Ca 교환의 존재 여부와 그 역할의 존재 가능성을 추구하여 보고자 하였다. 흰쥐의 좌심방은 전기장 자극(0.5msec, supramaximal voltage)으로 수축을 유발하고, 자극 빈도를 안정시 4Hz에서 0.4, 1, 8Hz로 변동시킬때 그 수축 장력에서 특징적인 역 사다리 효과(negative staircase effect)가 나타내었으나, 이때 $^{45}Ca$ 섭취는 저빈도로 갈수록, 또한 고빈도로 갈수록 증가되는 이원적인 증가를 나타내었다 자극 빈도를 4Hz 에서 0.4Hz로 변동시에는 수축 장력이 특징적인 삼단계 변환, 즉 급격히 증가하는 첫단계에 이어 급격하게 감소하는 이단계와 안정되어지는 삼단계로 나타났다. $^{45}Ca$ 섭취도 장력 변동과 같은 양상으로 처음 30초 동안에 현저하게 증가한 후 감소되었다. Na-Ca 억제 약물인 benzamil은 $10^{-5}M$에서부터 $3{\times}10^{-4}M$까지 용량에 비례하여 특히 초기의 장력증가를 봉쇄하였다. Bay K-8644$(3{\times}10^{-5}M)$ 처치는 자극 빈도 감소에 따른 수축력 증가를 현저하게 항진시켰으며, benzamil처치는 이때에도 억압을 나타내었다. Verapamil $3{\times}10^{-5}M$ 전처치시에는 4Hz 자극시의 수축 운동은 완전히 소실시켰으나, 0.4 혹은 1 Hz로 바꿈에 따라 수축 운동이 재현되었다. 이때 $^{45}Ca$ 섭취는 verapamil을 전처치하지 않은 경우보다 현저하게 항진되었다. 이상의 결과로 보아, 흰쥐의 좌심방에서 자극 빈도 감소후에는, 먼저 역방향 Na-Ca 교환에 의해 calcium이온이 세포내로 유입되어 수축운동의 항진이 유발되고, 이어 Na-Ca 교환이 정방향으로 변환되어 calcium이온을 세포밖으로 유출시킴에 따라 수축 운동이 감소된다고 생각한다. Na-Ca exchange transports calcium ion either into (reverse mode Na-Ca exchange) or out of the cell (forward mode Na-Ca exchange) according to the direction of driving force produced by the changes in ratio of intra- and extra-cellular Na concentrations. Thus, Na-Ca exchange is regarded as the regulator of myocardial contraction. However, the existence of reverse mode Na-Ca exchange and its role in myocardial contraction is still questioned. Present study was performed to identify the presence of reverse mode Na-Ca exchange and its possible involvement in the regulation of myocardial contraction in rat heart. Using the left atria of rat, contraction was induced by electrical field stimulation (EFS, 0.5 msec duration and supramaximal voltage). Changing of the stimulation frequencies from resting 4 Hz to 0.4, 1 or 8 Hz caused typical negative staircase effect in twitch tension, but $^{45}Ca$ uptake showed bimodal increase. When the stimulation frequency was abruptly changed from 4 Hz to 0.4 Hz the atrial twitch tension showed three phased-enhancement, that is, the initial rapid increase (the first phase) followed by rapid decrease (the second phase) and stabilization (the third phase). $^{45}Ca$ uptake was equivalent to tension, i.e. initial significant increase in first 30 second and then decrease. Benzamil treatment abolished the first phase of increase in a dose dependent manner from $10^{-5}\;to\;3{\times}10^{-4}M.$ Bay k 8644 $(3{\times}10^{-5}M)$ treatment enhanced the inotropy induced by frequency reduction and abolished the second and third phase decreases. Benzamil treatment also suppressed the contraction stimulated by Bay K 8644. Although the contraction at 4 Hz stimulation was completely abolished by verapamil $3{\times}10^{-5}\;M$ pretreatment, the contraction reappeared as soon as the stimulation frequency was changed into 0.4 or 1 Hz and interstingly,$^{45}Ca$ uptake were significantly higher than no treatment. From these results, it is concluded that reduction of stimulation frequency causes calcium influx by the reverse mode Na-Ca exchange, resulting in initial rapid increase of twitch tension. then it turns into forward mode exchange to efflux the calcium, resulting in decrease of the twitch tension in left atria of rat.

Studies on the Regulation of Calcium Activity in Myocardial Contraction

고창만,홍사석,Ko, Chang-Mann,Hong, Sa-Suk The Korean Society of Pharmacology 1990 대한약리학잡지 Vol.26 No.2

전기장 자극으로 수축을 유발한 흰쥐 좌심방에서, 자극 빈도 변경에 따른 수축 운동의 변동에 미치는, 여러 경로를 통한 수축 유발 calcium의 영향을 검색하므로, 각 경로가 심근 수축에 미치는 영향을 추구하였다. 흰쥐 좌심방은 자극 빈도를 급격하게 낮추므로, 특징적인 삼단계 변동을 나타내었다. 즉, 처음의 급격한 수축 장력증가와, 두번째 일시적인 빠른 장력감소, 이어서 세번째로 수축장력의 유지단계로 나타났으며, 이때 수축장력은 고빈도 자극시의 2배 정도가 되었다. Caffeine처치는 이와같은 자극빈도 하강에 따른 수축 장력의 증가를 현저하게 억압하였다. Verapamil은 고빈도 자극시 수축 운동을 완전히 소실시켰으나, 저빈도 자극으로 변경시에는 verapamil 존재하에서도 수축 운동이 소생되었다. 한편 ouabain처치나 영양액내 sodium 배제시에는 저빈도 자극으로 나타나는 특징적인 두번째 단계의 변동이 소실되었다. 이러한 결과로 보아, 심근막의 calcium통로는 세포내 유지에 필수불가결한 경로이며, 심근 수축 유발 calcium의 주된 기원은 근 소포체로 부터 유리되는 것으로 믿어진다. 또한 sodium-calcium교환은 세포내 sodium농도의 변동에 따라 수축 유발 calcium양 형성에 조절 인자로서의 기능을 갖는 것으로 추측된다. Influences of trigger calcium on myocardial contraction from several sources were investigated on the frequency reduction-induced changes of contraction in rat left atria driven by electrical field stimulation. Rat atria elicited characteristic three phase-changes according to frequency reduction: the first rapid rise in twitch tension, the second transient fast decrease in tension and the third maintenance of twitch tension at about 200% of resting tension during high frequency. Caffeine treatment enormously suppressed the frequency reduction-induced twitch tension increase. The atrial contraction during high frequency vanished after verapamil treatment. But, during low frequency, atrial contraction revived in the presence of verapamil. Ouabain treatment and sodium depletion in superfusing solution abolished the characteristic second phase with slow frequency. These results suggest that slow calcium channel is an indispensable calcium entry route and calcium release from sarcoplasmic reticulum is an major source for trigger calcium in cardiac contraction. And sodium-calcium exchange has a modulatory roles in the regualtion of trigger calcium according to the changes of intracellular sodium concentration.

심근 수축에 있어서 Calcium 이온의 기원에 관한 약리학적 연구

고창만(Chang Mann Ko),김경환(Kyung Hwan Kim) 대한약리학회 1994 대한약리학잡지 Vol.30 No.1

Na-Ca 교환은 calcium 이온을, 세포 내외의 Na 이온 농도차에 의해서 형성되는 원동력의 방향에 따라, 세포내로(역방향 Na-Ca 교환), 혹은 세포밖으로(정방향 Na-Ca 교환) 이동시킨다. 그러므로 Na-Ca 교환은 심근 수축 운동의 조절 기전의 하나로 받아 들여지고 있다. 그러나, 세포내의 Na 이온 농도는 항상 세포외의 농도보다 낮으므로, 역방향 Na-Ca 교환의 존재와 아울러 이의 심근 수축에 있어서의 역할 가능성에 대해 많은 연구자들이 회의를 가지고 있는 것이 사실이다. 그러므로 본 연구는 흰쥐의 좌심방을 이용하여, 역방향 Na-Ca 교환의 존재 여부와 그 역할의 존재 가능성을 추구하여 보고자 하였다. 흰쥐의 좌심방은 전기장 자극(0.5msec, supramaximal voltage)으로 수축을 유발하고, 자극 빈도를 안정시 4Hz에서 0.4, 1, 8Hz로 변동시킬때 그 수축 장력에서 특징적인 역 사다리 효과(negative staircase effect)가 나타내었으나, 이때 ⁴⁵Ca 섭취는 저빈도로 갈수록, 또한 고빈도로 갈수록 증가되는 이원적인 증가를 나타내었다 자극 빈도를 4Hz 에서 0.4Hz로 변동시에는 수축 장력이 특징적인 삼단계 변환, 즉 급격히 증가하는 첫단계에 이어 급격하게 감소하는 이단계와 안정되어지는 삼단계로 나타났다. ⁴⁵Ca 섭취도 장력 변동과 같은 양상으로 처음 30초 동안에 현저하게 증가한 후 감소되었다. Na-Ca 억제 약물인 benzamil은 10^-5M에서부터 3 × 10^-4M까지 용량에 비례하여 특히 초기의 장력증가를 봉쇄하였다. Bay K-8644(3 × 10^-5M) 처치는 자극 빈도 감소에 따른 수축력 증가를 현저하게 항진시켰으며, benzamil처치는 이때에도 억압을 나타내었다. Verapamil 3 × 10^-5M 전처치시에는 4Hz 자극시의 수축 운동은 완전히 소실시켰으나, 0.4 혹은 1 Hz로 바꿈에 따라 수축 운동이 재현되었다. 이때 ⁴⁵Ca 섭취는 verapamil을 전처치하지 않은 경우보다 현저하게 항진되었다. 이상의 결과로 보아, 흰쥐의 좌심방에서 자극 빈도 감소후에는, 먼저 역방향 Na-Ca 교환에 의해 calcium이온이 세포내로 유입되어 수축운동의 항진이 유발되고, 이어 Na-Ca 교환이 정방향으로 변환되어 calcium이온을 세포밖으로 유출시킴에 따라 수축 운동이 감소된다고 생각한다. Na-Ca exchange transports calcium ion either into (reverse mode Na-Ca exchange) or out of the cell (forward mode Na-Ca exchange) according to the direction of driving force produced by the changes in ratio of intra- and extra-cellular Na concentrations. Thus, Na-Ca exchange is regarded as the regulator of myocardial contraction. However, the existence of reverse mode Na-Ca exchange and its role in myocardial contraction is still questioned. Present study was performed to identify the presence of reverse mode Na-Ca exchange and its possible involvement in the regulation of myocardial contraction in rat heart. Using the left atria of rat, contraction was induced by electrical field stimulation (EFS, 0.5 msec duration and supramaximal voltage). Changing of the stimulation frequencies from resting 4 Hz to 0.4, 1 or 8 Hz caused typical negative staircase effect in twitch tension, but ⁴⁵Ca uptake showed bimodal increase. When the stimulation frequency was abruptly changed from 4 Hz to 0.4 Hz the atrial twitch tension showed three phased-enhancement, that is, the initial rapid increase (the first phase) followed by rapid decrease (the second phase) and stabilization (the third phase). ⁴⁵Ca uptake was equivalent to tension, i.e. initial significant increase in first 30 second and then decrease. Benzamil treatment abolished the first phase of increase in a dose dependent manner from 10^-5 to 3 × 10^-4M. Bay k 8644 (3 × 10^-5M) treatment enhanced the inotropy induced by frequency reduction and abolished the second and third phase decreases. Benzamil treatment also suppressed the contraction stimulated by Bay K 8644. Although the contraction at 4 Hz stimulation was completely abolished by verapamil 3 × 10^-5 M pretreatment, the contraction reappeared as soon as the stimulation frequency was changed into 0.4 or 1 Hz and interstingly,⁴⁵Ca uptake were significantly higher than no treatment. From these results, it is concluded that reduction of stimulation frequency causes calcium influx by the reverse mode Na-Ca exchange, resulting in initial rapid increase of twitch tension. then it turns into forward mode exchange to efflux the calcium, resulting in decrease of the twitch tension in left atria of rat.

해명 회장 운동에 대한 아드레나린성 ${\alpha}$-수용체에 관한 연구

고창만,Ko, Chang-Mann 대한약리학회 1983 대한약리학잡지 Vol.19 No.1

Intestine is innervated by an interconnected plexus of both sympathetic and parasympathetic nerve fibers. Sympathetic influence causes inhibition of intestinal motility mediated by both ${\alpha}-\;and\;{\beta}-adrenergic$ receptors. The mechanism of intestinal relaxation by ${\beta}-receptors$ has been extensively studied, but the function of ${\alpha}-receptors$ in intestinal motility is still unclear. Although it is suggested that catecholamine reduces acetylcholine release and this may play an important role in ${\alpha}-receptor$ mediated intestinal relaxation, there is no definite evidences about the mechanism and site of action of ${\alpha}-receptor$ mediated relaxation. In this experiment, therefore, the effect and site of action of ${\alpha}-receptor$ agonists were investigated in the guinea pig ileum using electrical field stimulation. The results are summarized as follows : 1) Electrical field stimulation elicited tonic contraction in isolated guinea pig ileum ana this contraction was completely inhibited by the pretreatment of tetrodotoxin or atropine. 2) Norepinephrine, epinephrine and dopamine inhibited the contraction induced by electrical field stimulation but methoxamine and phenylephrine had little effects. 3) Inhibitory effects of norepinephrine and dopamine was partially blocked by yohimbine and phentolamine pretreatment. But haloperidol and propranolol pretreatment cause no effects on the electrical field stimulation induced contraction. Inhibitory effect of dopamine was completely blocked by both haloperidol and yohimbine pretreatment. 4) Inhibitory effects of norepinephrine and dopamine were little affected by the pretreatment with hexamethonium. It is suggested that electrical field stimulation causes tonic contraction of guinea pig ileum by releasing acetylcholine from postganglionic fiber, and this release is blocked by presynaptic ${\alpha}-receptor$ activation.

고양이에서 체표냉각에 따른 심혈관계 변동에 관한 연구

안영수(Young Soo Ahn),고창만(Chang Mann Ko),이우주(Woo Choo Lee) 대한약리학회 1983 대한약리학잡지 Vol.19 No.1

Hypothermia is an essential preparatory procedure for cardiac surgery, which lows the metabolic rate and myocardial oxygen demand. However, hypothermia itself is a stress enough to change the tonus of sympathoadrenal system, especially the cardiovascular responses to the catecholamines. It is reported that the positive chronotropic and inotropic response of catecholamines is exaggerated during hypothermia because of decreased norepinephrine uptake at the junctional cleft or decreased catecholamine metabolism. On the other hand, there are evidences of diminished catecholamines responses in low temperature ana further, interconversion of adrenergic receptors is also suggested. Present investigation was planned to observe the cardiovascular changes and its responses to catecholamines during surface hypothermia in cat. Healthy mongrel cats, weighing 2 ~ 3 kg, anesthetized with secobarbital(30 mg/kg), were permitted to hypothermia by external cooling technic. Esophageal temperature, ECG (lead II), heart rate, left ventricular pressure with dP/dt, carotid artery pressure and left ventricular contractile force were monitored with Polygragh (Model 7, Grass), and the respiration was maintained with artificial respirator (V 5 KG, Narco). Followings are summarized results. 1) Surface cooling caused progressive decrease of body temperature and reached l8.8 ± 0.8˚C and 16.9 ± 0.6˚C in 120 and 150 min respectively, after immersion into ice water, and ventricular fibrillation was developed at 20.4 ± 0.65˚C. 2) Heart rate, blood pressure and myocardial contractility were decreased after initial increase as the body temperature falls. 3) Systolic and diastolicdd P/dt of left ventricular pressure were decreased and that the decrement of diastolic dP/dt was more marked. 4) On ECG, ST depression, Twave inversion and prolongation of PR interval were prominent in hypothermia, and moreover, the prolongation of PR interval was marked just prior to the development of ventricular fibrillation. 5) The cardiovascular responses to catecholamines, especially to isoproterenol, were suppressed under hypothermia.

The Role of Central Adrenergic Activity in Stress-induced Ulcerogenesis

김동구,고창만,경춘호,홍사석,Kim, Dong-Goo,Ko, Chang-Mann,Kyung, Choon-Ho,Hong, Sa-Suk The Korean Society of Pharmacology 1987 대한약리학잡지 Vol.23 No.2

The role of central adrenergic activity in the genesis of stress ulcers was investigated by intracerebroventricular (i.c.v.) administration of catecholamines and clonidine in pylorus-ligated rats restrained for 4 hours at a temperature of $4^{\circ}C$. 1. The stress-induced ulceration was markedly decreased by the i.c.v. administration of norepinephrine, epinephrine, dopamine or low dose of clonidine. 2. After an i.c.v. administration of norepinephrine or epinephrine, the volume of gastric juice, and both acid and pepsin secretion were markedly decreased. 3. Dopamine or a low dose of clonidne decreased the volume of gastric juice and acid secretion but did not affect pepsin secretion. 4. Isoproterenol caused a decrease in the volume of gastric juice and acid secretion, however, the ulcerogenesis was similar to that of the control. 5. Gastric function as well as ulcerogenesis was little affected by a high dose of clonidine. From the above results, it is suggested that central adrenergic activation inhibits cold-restraint induced ulcerogenesis via adrenergic alpha and dopaminergic receptors, and that this effect may be mediated by a decrease in gastric acid secretion. It is also suggested that other factors may be involved in this antiulcerogenic effect. 스트레스로 인한 위궤양형성에 중추성 교감신경의 영향여부를 추구하기 위하여 norepinephrine, epinephrine, dopamine, isoproterenol 및 clonidine을 흰쥐의 뇌실내로 투여 하고 한냉 환경 $(4^{\circ}C)$에서 4시간 구속방치하여 위 분비기능의 변동과 궤양 발생 정도를 검색하여 다음과 같은 결과를 얻었다. 1. Norepinephrine, epinephrine, dopamine및 소량의 clonidine 처치로 궤양 발생이 현저하게 감소하였다. 2. Norepinephrine또는 epinephrine 처치군에서는 위액분비, 산분비 및 펩신 분비의 감소와 궤양 발생 감소가 초래되었다. 3. Dopamine혹은 소량의 clonidine 처치군에서는 궤양 발생의 감소와 위액분비 및 산분비 감소가 초래되었으나 펩신 분비는 변동 없었다. 4. Isoproterenol처치군에서는 궤양 발생과 펩신 분비는 대조군과 차이 없고, 위액분비 및 산분비의 감소만 나타났다. 5. 대량의 clonidine 투여군에서는 궤양발생, 산분비 및 펩신분비 모두 변동없이 약간의 위액분비 감소가 나타났다 이상의 결과로 보아 중추성 교감신경자극은 궤양 형성을 억압하는 작용이 있고, 이에는 교감신경성 ${\alpha}$-수용체 및 도파민성 수용체가 관여된다고 믿어지며, 이 효과는 위액분비 감소 및 산 분비 감소작용과 아울러 또 다른 요인이 관여한다고 추측된다.

흰쥐 심근의 역 사다리 효과에 있어서 생후 연령에 따른 $Na^+\;-Ca^{2+}$ 교환의 역할에 관한 연구

이해용,김순진,고창만,Lee, Hae-Yong,Kim, Soon-Jin,Ko, Chang-Mann 대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.6

Recent reports revealed that the $Na^+-Ca^{2+}$ exchangers and feet structures of sarcoplasmic reticulum(SR) are located in close vicinity in the specific compartment. Therefore, we investigated the possibility that the $Na^+-Ca^{2+}$ exchanger may decrease the tension development by transporting the $Ca^{2+}$ out of the cell right after it released from SR, on the basis of this anatomical proximity. We exammined the negative force-frequency relationship of the developed tension in the electrically field stimulated left atria of postnatal developing rat(1, 3 day, 1 week and 4 week old after birth). Cyclopiazonic $acid(3{\times}10^{-5}\;M)$ treatment decreased the developed tension further according to postnatal age. $Monensin(3{\times}10^{-6}\;M)$ treatment did not increase the maximal tension in 4 week-old rat, preserving negative staircase, while the negative staircase in the younger rat were flattened. $Ca^{2+}$ depletion in the buffer elicited more suppression of the maximal tension according to the frequency in all groups except the 4 week-old group. The % decrease of the maximal developed tension of 4 week-old group at 1 Hz to that of 0.1 Hz after $Na^+$ and $Ca^{2+}$ depletion was only a half of those of the yonger groups. Taken together, it is concluded that the $Na^+-Ca^{2+}$ exchange transports more $Ca^{2+}$ released from SR out of the cell in proportion to the frequency, and this is responsible for the negative staircase effect of the rat heart.

스트레스성 궤양발생에 대한 중추 아드레날린성 활성도의 역할

김동구(Dong-Goo Kim),고창만(Chang Mann Ko),경춘호(Choon Ho Kyung),홍사석(Sa Suk Hong) 대한약리학회 1987 대한약리학잡지 Vol.23 No.2

스트레스로 인한 위궤양형성에 중추성 교감신경의 영향여부를 추구하기 위하여 norepinephrine, epinephrine, dopamine, isoproterenol 및 clonidine을 흰쥐의 뇌실내로 투여 하고 한냉 환경 (4˚C)에서 4시간 구속방치하여 위 분비기능의 변동과 궤양 발생 정도를 검색하여 다음과 같은 결과를 얻었다. 1. Norepinephrine, epinephrine, dopamine및 소량의 clonidine 처치로 궤양 발생이 현저하게 감소하였다. 2. Norepinephrine또는 epinephrine 처치군에서는 위액분비, 산분비 및 펩신 분비의 감소와 궤양 발생 감소가 초래되었다. 3. Dopamine혹은 소량의 clonidine 처치군에서는 궤양 발생의 감소와 위액분비 및 산분비 감소가 초래되었으나 펩신 분비는 변동 없었다. 4. Isoproterenol처치군에서는 궤양 발생과 펩신 분비는 대조군과 차이 없고, 위액분비 및 산분비의 감소만 나타났다. 5. 대량의 clonidine 투여군에서는 궤양발생, 산분비 및 펩신분비 모두 변동없이 약간의 위액분비 감소가 나타났다 이상의 결과로 보아 중추성 교감신경자극은 궤양 형성을 억압하는 작용이 있고, 이에는 교감신경성 α-수용체 및 도파민성 수용체가 관여된다고 믿어지며, 이 효과는 위액분비 감소 및 산 분비 감소작용과 아울러 또 다른 요인이 관여한다고 추측된다. The role of central adrenergic activity in the genesis of stress ulcers was investigated by intracerebroventricular (i.c.v.) administration of catecholamines and clonidine in pylorus-ligated rats restrained for 4 hours at a temperature of 4˚C. 1. The stress-induced ulceration was markedly decreased by the i.c.v. administration of norepinephrine, epinephrine, dopamine or low dose of clonidine. 2. After an i.c.v. administration of norepinephrine or epinephrine, the volume of gastric juice, and both acid and pepsin secretion were markedly decreased. 3. Dopamine or a low dose of clonidne decreased the volume of gastric juice and acid secretion but did not affect pepsin secretion. 4. Isoproterenol caused a decrease in the volume of gastric juice and acid secretion, however, the ulcerogenesis was similar to that of the control. 5. Gastric function as well as ulcerogenesis was little affected by a high dose of clonidine. From the above results, it is suggested that central adrenergic activation inhibits cold-restraint induced ulcerogenesis via adrenergic alpha and dopaminergic receptors, and that this effect may be mediated by a decrease in gastric acid secretion. It is also suggested that other factors may be involved in this antiulcerogenic effect.

뇌실내 Calcitonin 투여로 인한 위산분비 억제에 대한 뇌내 신경전달체의 역할

장우익(Woo Ick Jang),이동기(Dong Ki Lee),권상옥(Sang Ok Kwon),고창만(Chang Mann Ko),현재헌(Jae Hun Hyun),김상태(Sang Tae Kim),이상인(Sang In Lee),최흥재(Heung Jai Choi),김경환(Kyung Hwan Kim) 대한내과학회 1991 대한내과학회지 Vol.40 No.5

N/A Peptides that are common to the brain and gut are thought to play intermediary roles as neurotransmitters or neuromodulators in the regulation of gut function. Calcitonin is a polypeptide hormone of 32 amino acid residues. Recently, much evidence has been accumulated to suggest that calcitonin may inhibit gastric acid secretion by a central action, but the neurohumoral pathways mediating the antisecretory effects of calcitonin in rats are not well elucidated. In the present study, using a gastric perfusion technique, the effects of ICV administration of calcitonin on gastric acid secretion stimulated by baclofen were investigated in rats. We also investigated whether the serotonergic system is involved in calcitonin's effect of gastric acid secretion. The results obtained were as follows: 1) ICV administration of baclofen stimulated gastric acid secretion in a dose-dependent manner. Central administration of baclofen was approximately 200-400 times more sensitive than subcutaneous administration. 2) Baclofen-induced gastric acid secretion was partially suppressed by bilateral vagotomy. 3) Gastric acid secretion stimulated by baclofen was markedly suppressed by ICV administration of calcitonin. 4) Depletion of brain serotonin with the neurotoxin 5, 7-dihydroxytryptamine did not influence calcitonin-induced gestric acid suppression. In this study it was demonstrated that centrally- administered calcitonin suppresses baclofen-induced gastric acid secretion. Also. it is suggested that the serotonergic system is not involved in calcitonin-induced gastric acid suppression.