Isoproterenol 의 장기비대 작용에 관한 연구

홍사석 ( S. S. Hong ),심치윤 ( C. Y. Shim ),강정호 ( J. H. Kang ) 대한내과학회 1964 대한내과학회지 Vol.7 No.5

L - Asparaginase 의 취독성에 대한 실험적 검토

홍사석 ( S. S. Hong ),김원준 ( W. J. Kim ),김경환 ( K. H. Kim ),김혜경 ( H. K. Kim ),김정숙 ( C. S. Kim ),김대현 ( D. H. Kim ),이용우 ( Y. W. Lee ) 대한내과학회 1973 대한내과학회지 Vol.16 No.8

Toxic effect of L-asparaginase(NSC 109229, Merck Sharp & Dohme) on pancreas after single repeated administration was studied in rabbits and rats. Rectal temperature was slightly elevated in rabbits at one hour after intravenous administration of L-asparagi

담즙분비와 Cyclic nucleotides간의 상호관계에 관한 연구

이향우,김원준,홍사석,조석준,홍사오,임중기,Lee, H.W.,Kim, W.J.,Hong, S.S.,Cho, S.J.,Hong, S.U.,Lim, C.K. 대한약리학회 1982 대한약리학잡지 Vol.18 No.1

Bile formation is a complex process comprised of three separate physiologic mechanism operating at two anatomical sites. At present time, it was known that at least two processes are responsible for total canalicular secretion at the bile canaliculus. One of the processes is bile salt-dependent secretion (BSDS) hypothesis that the active transport of bile salts from plasma to bile provided a primary stimulus for bile formation: the osmotic effect of actively transported bile acid was responsible for the movement of water and ions into bile. The other process is bile salt-independent secretion (ESIS), which is unrelated to bile salt secretion at the canaliculus and which may involve the active transport of sodium. The third process for bile formation involves the biliary ductal epithelium. Secretin-stimulated bile characteristically contained bicarbonate in high concentration. Therefor, it was suggested that secretin stimulated water and bicarbonate secretion from the biliary ductules. One the other hand, it was found that a large amounts of cAMP was present in canine bile but no apparent relationship between bile salt secretion and cAMP content in dog bile. However, bile flow studies in human have demonstrated that secretin and glucagon increase bile cAMP secretion as does secretin in baboons. Secretin increases baboon bile duct mucosal cAMP levels in addition to bile CAMP levels suggesting that in that species secretin-stimulated bile flow may be cAMP mediated. It has been postulated that glucagon and theophylline which increase the bile salt-independent secretion in dogs might act through an increased in liver cAMP content. In a few studies, the possible role of cAMP on bile formation has teen tested by administration of an exogenous derivative of cAMP, dibutyryl cAMP. In the rat, DB cAMP did not modify bile flow, but injection of DB cAMP in the dog promoted an increase in the bile salt-independent secretion. Because of these contradictory results, this study was carried out to examine the relationship between cyclic nucleotides and bile flow due to various bile salts as well as secretin or theophylline. Experiments were performed in rabbits with anesthesia produced by the injection of seconal(30 mg/kg). Rabbits had the cystic duct ligated and the proximal end of the divided common duct cannulated with an appropriately sized polyethylene catheter. A similar catheter was placed into the inferior vena cava for administration of drugs. Bile was collected for determination of cyclic nucleotides and total cholate in 15 min. intervals for a few hours. The results are summerized as followings. 1) Administrations of taurocholic acid or chenodeoxycholic acid increased significantly the concentrations of cAMP and cGMP in bile of rabbits. 2) Concentration of cAMP in bile during the continuous infusion of ursodeoxycholic acid, was remarkedly increased in accordance with the increase of bile flow, while on the contrary concentration of cGMP in bile was decreased significantly. 3) Dehydrocholic acid and deoxycholic acid significantly increased bile flow, total cholate output and cyclic nucleotides in bile. 4) Only cAMP concentration in bile was significantly increased from control value by secretin, while theophylline increased cAMP as well as cGMP in rabbit bile. 5) In addition, the administration of secretin to taurocholic acid-stimulated bile flow increased cAMP while theophylline produced the increases of cAMP and cGMP in bile. 6) The administration of insulin to taurocholic acid-stimulated bile flow decreased cAMP concentration, while on the contrary cGMP was remarkedly increased in rabbit bile.

Cholecystokinin-pancreozymin의 식도절편 수축반응에 미치는 phenoxybenzamine의 영향

조태순(T.S. Cho),김원진(W.J. Kim),홍사석(S.S. Hong) 대한약리학회 1980 대한약리학잡지 Vol.16 No.1

In this study, the effects of phenoxybenzamine and related drugs on the action of CCK-PZ and caerulein were examined in isolated gall bladder of guinea pig and higher esophagus strip of fowl. The strips were placed in a bath containing Locke-Ringer solution maintained at 38˚C. Oxygen was continuously bubbled through the solution. The contractile response was measured isometrically by a force displacement transducer connected to polygraph. In isolated gall bladder preparation caerulein produced contractile response of CCK-PZ type, but the relative potency on a weight basis was 30 times stronger than CCK-PZ. The response of caerulein or CCK-PZ was not blocked by cholinergic blocking agent and both alpha and beta adrenergic blockades, however, the response of caerulein or CCK-PZ was exceptionally blocked by phenoxybenzamine. In isolated esophagus strip CCK-PZ with high concentration produced marked contraction which was not modified by atropine and other blocking agents, whereas the response was blocked by phenoxybenzamine. These results lead to the conclusion that phenoxybenzamine inherently inhibits the contractile response of CCK-PZ and caerulein on esophagus and other smooth muscle.

흰쥐의 위산(胃酸)분비에 대한 고장(高張)포도당용액의 영향

김혜영,조태순,홍사석,Kim, H.Y.,Cho, T.S.,Hong, S.S. 대한약리학회 1976 대한약리학잡지 Vol.12 No.1

Using modified technique of Schmidt et al, as described previously (Korean J. Pharmacol 9 : 17, 1973), the stomach of female rats were perfused with physiological saline under urethane anesthesia. The acid-secretory response of the perfused stomach to i.v. hypertonic glucose (50%), casein hydrolysate (20%) or saline (6%) solution were studied with or without histamine or methacholine stimulation. A significant decrease of acid secretion from the rat stomach was induced by i.v. hypertonic glucose or saline solution. The histamine-stimulated acid secretion was also decreased by simultaneous administration of the hypertonic glucose or saline. However, methacholine-stimulated acid response was not affected by the hypertonic glucose. Intravenous infusion of 20% casein hydrolysate solution resulted in an increase in acid output from the stomach under histamine stimuli. These results lead to the conclusion that the inhibitory responses of acid secretion due to i.v. hypertonic glucose solution are brought through the effect of histaminergic, not cholnergic mechanism(s) in the gastric secretion.

산조인의 중추신경 및 심혈관계에 대한 약리작용

안영수,김경환,조태순,김원준,홍사석,Ahn, Y.S.,Kim, K.H.,Cho, T.S.,Kim, W.J.,Hong, S.S. 대한약리학회 1982 대한약리학잡지 Vol.18 No.1

Zizyphus seed(Zizyphus vulgaris Lamark var. Spinosus Bunge) has long been used as hypnotics and sedatives in oriental medicine, and it is reported that the Zizyphus seed elicited a variety of pharmacologic actions besides CNS depression. Present study was undertaken to investigate the effects of Zizyphus seed on the central nervous system and on the blood pressure. The effect of Zizyphus seed on the central nervous system was measured by the influence of thiopental sleeping time and by inhibition of chemical convulsion (strychnine and pentylenetetrazol induced). Blood pressure changes by Zizyphus extract and its mode of action were investigated. The ground Zizyphus seed was extracted with hexane and methanol, consecutively and the supernatants were discarded. The precipitate was re-extracted with distilled water and the supernatant was evaporated to a dark-brownish sticky liquid, which was used as Zizyphus seed extract in this study after dissolving in saline prior to experiment. The results are as follows. 1) Zizyphus seed extract caused marked prolongation of the thiopental sleeping time in mice. 2) The chemical convulsion by strychnine and pentylenetetrazol, and the mortality by them in chicks were not affected by pretreatment of Zizyphus seed extract. 3) Zizyphus seed extract produced transient fall of blood pressure in the cat, and this hypotentive effect was blocked partially by atropine but not affected by bilateral vagotomy and/or hexamethonium, nor propranolol and, chlorpheniramine and/or cimetidine. With the above results, it may be suggested that the water extract of Zizyphus seeds contains components producing CNS depression and hypotension. Furthermore it is felt that the cholinergic effect, but not the adrenergic or histaminergic, is partly responsible for the hypotensive effect of Zizyphus seed extract.

흰쥐의 위(胃).십이지장(十二指腸) 동시관류표본(同時灌流標本)에 대(對)한 Caerulein의 작용(作用)

조태순(Cho, T.S.),신창진(Shin, C.J.),이병학(Lee, B.H.),홍사석(Hong, S.S.) 대한약리학회 1973 대한약리학잡지 Vol.9 No.2

Modifying the technique described by Schmidt, et al. (1972) the duodenum and stomach of female rats were perfused separately and contiunously with saline solution under urethane anesthesia. Secretory response of caerulein (Prof. V. Erspamer, F.I. 6934 Caerulein, Farmitalia, Italia), a gastrin or CCK-PZ like peptide, on acid, pepsin, bicarbonate and amylase were studied with and without simultaneous administration of secretin, CCK-PZ or other agents known secretory suppressives. A significant increase of acid, pepsin and amylase output was induced by intravenous infusion of caerulein. The response of acid secretion by caerulein in doses of 140 ng/100g/hr was equivalent to the response of histamine in the doses of 280μg/100g/hr and on a weight basis the potency of caerulein was approximately 2,000 times greater than histamine in rats. Acid secretory response of caerulein in the doses of 140 ng/100 g/hr was inhibited by simultaneous infusion of secretin in the doses of 0.2 u/ 100 g/hr, and the acid response was partly inhibited by concomitant infusion of histamine in the doses of 280μg/100g/hr, but the response was enhanced by infusion of CCK-PZ in the doses of 0.2 u/100 g/hr. The secretory response of both aicd and enzymes were inhibited following administration of atropine in doses of 0.2 mg/100 g, but the response were not affected by hexamethonium in doses of 0.5 mg/100 g. In summary, it is concluded that caerolein is every effective in an increase of acid, pepsin and amylase secretion in rats through, possibly in part, the muscarinic and/or histaminic mechanism(s).

토끼 담낭절편에 대한 Caerulein의 작용

조태순(Cho, T.S.),이우주(Lee, W.C.),홍사석(Hong, S.S.) 대한약리학회 1974 대한약리학잡지 Vol.10 No.1

The isolated rabbit gall bladder strips were prepared according to the technique described by Amer and Becvar (1969). The strips were placed in a bath containing 100 ml of Locke-Ringer solution maintained at 38˚C. Oxygen was continuously bubbled through the solution. The tension of the muscle strip was initially adjusted to 0.7g. The contractile response was measured isometrically by a force-displacement transducer connected to a polygraph. The effect of a number of autonomic drugs were studied for their interaction with caerulein (Prof. V. Erspamer, F.I. 6934 Caerulein, Farmitalia, Italia), a gastrin or CCK.PZ like peptide, on isolated rabbit gall bladder strips. In this preparation caerulein produced contractions of CCK-PZ type, but the relative potency on a weight basis was 40 times that of CCK-PZ. The response of caerulein was not modified by either cholinergic or alpha or beta adrenergic blockade. However, the response of caerulein and of barium on the strips were prevented by papaverine or aminophylline. Isoproterenol, papaverine or aminophylline alone relaxed the preparation whereas caerulein, CCK-PZ, acetylcholine, serotonin, histamine or barium chloride contracted the preparation. In summary, it is concluded that caerulein on the gall bladder strip seems to act independently of the autonomic nervous system and mediated via mechanisms apparently similar to those involved in the action of barium chloride.

한국산(韓國産) 사독(蛇毒)에 관(關)한 실험적(實驗的) 연구(硏究)

김원준(Kim, W.J.),안영수(Ahn, Y.S.),김주덕(Kim, J.D.),김세환(Kim, S.W),홍사석(Hong, S.S.) 대한약리학회 1976 대한약리학잡지 Vol.12 No.2

Agkistrodon halys (Crotalidae) is the only species of poisonous snakes in Korea, and is divided into three subspecies; Agkistrodon bromhoffii brevicaudus, Agkistrodon calaginosus and Agkistrodon saxatilis. With the three venoms, the pharmacological actions on the cardiovascular system and intestine as well as some toxicological characteristics were studied. In addition, the precipitin test in an agar gel medium was employed for immunological comparison of the venoms and the sera of envenomed patients. The results obtained were as follows: Lyophilized venoms contained solids of 211 ~ 273mg/ml, and LD50 to mice were 1.73 and 0.86 mg/kg in venoms of Agkistrodon bromhoffii brevicaudus obtained on July and October respectively, and 0.40 and 0.32 mg/kg in Agkistrodon calaginosus and the venoms of Agkistrodon saxatilis obtained on October was 2.29 mg/kg. Isoelectric focusing of lyophilized snake venoms showed 19 to 22 protein fractions and 2 to 3 isoamylase fractions. Acute irreversible hypotension was caused by the intravenous injection of large doses of venoms in rabbits and cats, but at the small doses, acute hypotension followed by slow recovery. Little changes of cardiac movements by the venom injection despite of marked hypotension were showed except bradycardia and arrhythmia prior the death. Also no changes on the isolated rabbit atria by the snake venoms were noted. The hypotensive effect of the snake venoms was prevented by the bilateral vagotomy or atropine pretreatment (1 mg/kg), but they did not affect when already the hypotension has undergone. In the isolated rabbit duodenum, small doses of venom increased the phasic movement, while large doses decreased after spastic contraction. With the injection of venoms in dog, strong contraction of gall-bladder was caused and it was not blocked by the pretreatment with phenoxybenzamine (10 mg/kg) or atropine (1.4 mg/kg). In the venoms of Agkistrodon bromhoffii brevicaudus and Agkistrodon calaginosus, at least 5 antigenic components were detected, and four of them were shared in common with each other. Polyvalent antivenin (Wyeth Lab. USA) had three common precipitating antibodies with the venom of Agkistrodon bromhoffii brevicaudus and Akistrodon calaginosus. In the serum of envenomed patients, no precipitating antibodies were seen to the venoms and little changes in serum protein, GOT and GPT were observed. In conclusion, the snake venoms obtained in Korea were highly toxic and caused chiefly the vascular collapse leading to death. This vascular collapse was resulted largely by cholinergic effects, and not cardiotoxin of venoms. In human, it is likely that precipitating antibodies to venom were not produced by an envenomed incidence to poisonous snakes.

저온환경 적응에 있어서의 갑상선 Hormone의 변동

이향우(H.W. Lee),김원준(W.J. Kim),홍사석(S.S. Hong),김호석(H.S. Kim),홍사오(S.U. Hong) 대한약리학회 1981 대한약리학잡지 Vol.17 No.2

The importance of thyroid hormones for the survival of rats in the cold is along-established fact. Hypothyroid animals are unable to survive in a cold environment. It was also reported that acute exposure of rats, guinea pigs and rabbits to cold produced an increased secretion of TSH and thereby thyroid hormone secretion within 10 to 30 min, but this increase of thyroid activity disappeared quite rapidly during warming. However, in human study no significant difference was found in the concentration of T₄, TSH and cortisol between summer and winter. But plasma T₃ concentration was increased significantly in winter in 56 adult men. On the other hand, it has been also known that catecholamines are important in the maintenance of body temperature of rat exposured to cold. Abundant evidences suggest that the sympathetic nervous system is involved in the activation of nonshivering thermogenesis and that thyroid hormone metabolism and secretion are influenced by catecholamines and consequently by the activity of the sympatheticadrenal system. Many of the metabolic effects of catecholamines are associated with an increase in the level of cAMP mediated through activation of adenylate cyclase which converts ATP to cAMP. Other studies have shown that thyroid hormones affect the amount of adenylate cyclase present in the adipose tissue. On the other hand. it was also reported that a particulate cAMP phosphodiesterase activity in fat cells was modulated by the action of thyroid hormones. The objective of the present study was to determine the interaction between thyroid activity and cyclic nucleotides during acute exposure to cold. Albino rats weighing around 200 g were used as the experimental animal. The room temperature group was kept at 25˚C and the cold-exposured group was kept at 4˚C for 1 week or 2 weeks. Each group was subdivided into three subgroups; control, KI, and MTU group. At the end of experiment the animals were etherized and blood was taken from abdominal aorta for T₄, T₃ and cyclic nucleotides. The determinations of T₃, T₄ and cyclic nucleotides were carried out with a radioimmunoassay(RIA) method. The results were summerized as followings. 1) A significant increase of thyroid weight was observed in rats exposured to cold for 2 weeks. Furthermore, in rats administered MTU while to exposure to cold the thyroid weight was also increased significantly. 2) After 2 weeks T₃ concentration in the plasma of cold-exposured rats was significantly increased in KI group and MTU group as well as in control group. On the contrary, after 2 weeks of cold exposure T₄ level was decreased in control group. 3) In the case of cyclic nucleotides, plasma cAMP was increased in the control group after 1 or 2 weeks of cold exposure. However, cAMP level in plasma was rather significantly decreased in KI group and MTU group as well as in control group.