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담즙분비와 담낭수축에 미치는 Caerulein 및 자율신경계약물의 영향

Other Titles
 Effects of caerulein and autonomic drugs on the bile flow and gallbladder contraction 
Authors
 민병준 
Issue Date
1975
Description
의학과/박사
Abstract
[한글] 일찌기 Ivy 및 O1dberg는 담낭수축 인자인 cholecystokinin(CCK)을 발견하였고 Harper 및 Raper는 취효소( 酵素)분비 자극 인자인 pancreozymin(PZ)을 발견하였다. 그후 Jorpes 및 Mutt는 다각도로 검토하여 CCK와 PZ은 화학적으로 동일 물질임을 입증하게되었다. 일방 Erspamer 등은 오스트라리아산 개구리 Hyla caerulea의 피부에서 추출된 caerulein이 수종(數種)동물의 담낭을 효과적으로 수축시킴을 지적하였다. 이와같은 caerulein의 담낭수축작용의 역가는 Vagne 등에 의하면 무마취하(撫摩醉下)의 개에서 CCK 보다 중량비로 47배 강하다고 하고 趙등은 토끼의 담낭절편 실험에서 중량비로 40배강하다고 보고하였다. Nakayama 등과 Yanaura 등은 atropine, nicotine, procaine 그리고 tetrodotoxin에 의하여 척출담낭(剔出膽囊)은 영향이 없다고 보고하고 趙등은 토끼의 담낭절편 실험에서 norepinephrine, isoproterenol, phentolamine, dibenzyline 및 propranolol등의 자율신경계 약물에 의하여 영향을 받지 않았다고 보고하였다. 洪은 adrenaline 흑은 acetylcholine의 정맥주사는 담낭담즙압(膽囊膽汁壓)에 영향이 없으나 hexamethonium을 정맥주사할 경우에는 십이지장내 염산관류 또는 식이성 (食餌性)으로 인한 담낭담즙압 상승이 경감(輕減) 흑은 방지됨을 관찰하였고 atropine은 영향이 없고, 도리어 총수담관(總輸膽管) 폐쇄동물에서는 담낭담즙압 상승 경향을 나타낸다고 보고하였다. 담낭기능에 대한 신경지배 특히 미주신경 (迷走神經)의 영향에 관하여 학자간의 의견이 구구하다. Johnson 및 Hoyden은 고양이의 우측 미주신경 절단이 담낭수축을 억제하는 것을 관찰 보고하였고 그후에도 많은 연구가 있었다. 이러한 관찰 보고를 토대로 caerulein, CCK-PZ, secretin 및 수종 자율신경계 약물이 토끼, 고양이 및 개의 담낭수축작용에 미치는 영향에 대하여 관찰하였다. 토끼, 고양이 및 개를 urethane 흑은 secobarbital로 마취하여 토끼에서 총수담관에 삽관하여 10분 간격으로 배출되는 담즙을 채취하고 고양이에서는 담낭루를 조성하여 담낭관을 결찰한 후 담낭루관을 직접 polygraph recorder(Grass Model 7)에 연결하여 그압의 변동슬 묘사하였다. 개에서는 담낭루를 조성하고 담낭관을 결찰하여 caerulein 흑은 CCK-PZ에 의한 담낭담즙압 변동을 기록하면서 수종 자율신경계 약물의 영향을 관찰하였다. 담즙(膽汁)의 cholate는 Irvin 등의 방법으로, cholesterol은 Frankel 등의 방법으로, bilirubin은 Hiller의 방법으로 측정하였다. 이상의 실험으로 다음과 같은 결과를 얻었다. 1. Caerulein과 cholecystokinin-pancreozymin은 토끼의 담낭을 현저히 수축시키고 그 수축효력은 caerulein이 월등히 강하였으나 secretin은 담낭에 별 영향을 미치지 않았다. 2. Caerulein의 고양이 담낭수축반응은 미주신경 절단으로 저하되었으나 acetylcholine 혹은 methacholine의 담낭수축반응은 오히려 증가되었다. 3. 미주신경을 절단한 고양이에서는 caerulein에 의한 담즙배출량 저하 및 담즙산 배출 억제반응을 초래하였다. 4. Dibenzyline을 전처치한 개에서는 caerulein과 cholecystokinin-pancreozymin의 담낭 수축반응이 현저히 억제되었으나 propranolol, atropine 및 hekamethonium 전처치예에서는 별 영향이 없었다·. 이상 실험 결과로 보아 caerulein은 cholecystokinin-pancreozymin과 같은, 그러나 훨씬 강한 담낭수축반응을 나타내고 그 수축반응은 미주신경 절단으로 갇약되나 atropine, hexamethonium 흑은 교감신경계(交感神經系)의 α 및 β 수용체(受容體) 차단제 전처치로는 영향을 받지 않았다. 다만 dibenzyline 전처치로 수축효과가 저지되었으며 이는 α-수용체 봉쇄작용(封鎖作用)과는 무관한 것으로 사료된다.
[영문] Since Ivy and O1dberg (1928) postulated a mechanism of gallbladder contraction and evacuation caused by cholecystokinin, pancreozymin was also identified and had similar function on gallbladder (Harper and Raper. 1943: Jorpes and Mutt, 1966, 1970). Recently caerulein, an active decapeptide, is isolated from methanol extracts of the skin of the Australian frog Hyla caerulea by Erspamer and co-workers (1967) and synthetized by Anastasi and co-workers (1967). It displays a number of striking pharmacological actions on the vascular and extravasculur smooth muscles and on exocrine glands. One of the most evident effects is the contraction of both isolated and in situ gallbladder of various animal species. Caerulein was 47 times as potent as cholecystckinin-pancreofymin (CCK-PZ) on weight basis inconscious dogs (Vagne and Grossman, 1968) and 40 times as potent as CCK-PZ in studies of gallbladder stripes of rabbits (Cho et at. 1974). Nakayama et al. (1972) and Yanaura et al.(1974) reported that the cholecystokinetic action of caerulein was net influenced by atropine, nicotine, procaine and tetrodotoxin in the isolated gallbladder. Cho et at. (1974) demonstrated that the isolated gallbladder stripes of rabbits was not influenced by norepinephrine, isoproterenol. phentolamine , dibenzyline and propranolol. Heng et al. (1956, 1960) reported that the intraveous injection of adrenaline or acetylcholine produced no changes in the biliary pressure, but the hexamethonium chloride produced a dropin the biliary pressure by itself and prevented the pressure response to either the irrigation with HCI or feeding even in the animal unanesthetized dogs occluded duct. On the other hand. atropine produced no decrease but rather an enhancement of the response to the irrigation of Thiry-Vella loop with HCI in the animals with occluded common ducts. It is controversial to the influencing of vagus nerve upon the gallbladder function. Johnson and Hoyden (1943) working on cats observed that the rate of emptying of the gallbladder was slower after section of the right vagus nerve. Recently many investigators working on cats, dogs, and rabbit observed that the rate of emptying of the gallbladder was slower after section of the vagus nerve(Snape, 1948: Lundman et al., 1964: Fagerberg et at., 1970). Present study was undertaken to observe the effects of caerulein, CCH-PZ secretin and various autonomic drugs upon the contraction of gallbladder in the rabbits, cats and dogs. Forty-five white rabbits of both sexes weighing 1.8kg in average, 15 cats weighing 4kg in average and 21 dogs weighing 9kg in average were anesthetized with urethane (1.4 gm/kg s, c.) or secobarbital (37mg/kg i.p. or i.v ), then the procedures were carried but with sterile technique as far as possible through midline incision on a supine position. In the rabbits, choledochostomy was made and collected the bile in 10 minutes intervals before and after cystic duct ligation. In the cats, cholecystostomy and cystic duct ligation were made and the cholecystostomy tube connected to a direct polygraph recorder (Grass Model 7) by saline filled rubber tube. On the other series the bile collected through the cholecystostomy tube in 30 minutes inter-vals. The gallbladder pressure and analyzed bile components observed comparatively before and after vagotomy using the caerulein. In the dogs the cholecystostomy and cystic duct ligation was performed same as the cats and recorded the gallbbadder contraction by the caerulein and cholecystokinin-pancreozymin which was certain affecting various autonomic drugs. The cholate was measured by the method of Irvin et at. (1944) , cholesterol by Frankel et al. (1963) and the bilirubin by Hiller (1957). Summary The actions of caerulein, cholecystokinin-pancreozymin (CCK-PZ) and various autonomic drugs on the gallbladder were investigated in experimental animals. The choleystokinetic potency and chanties of bile components were also observed. 1. The effects of caerulein and CCK-PZ were marked contraction of gallbladder in situ, and the caerulein was more Potent than CCK-PZ on the weight basis, but the secretin did not influenced on the gallbladder in situ. 2. The cholecystokinetic action of caerulein upon the vagotomized cat's gallbladder was decreased in potency, butt acetylcholine and methacholine increased. 3. In the vagotomized cat the gallbladder evacuation was decreased by the caerulein. 4. The intravenous injection of dibenzyline produced marked decrease of cholecystokinetic effect of caerulein and CCK-PZ but it's cholecystokinetic action was not reduced by prepranolol, atropine and hexamethonium. These results lead to the conclusion that the actions of caerulein are similar to those of CCK-PZ but always more potent than CCK-PZ. The cholecystokinetic activity was decreased after vagotomy, but net influenced by atropine, hexamethonium and alpha and beta adrenergic blocking agents. Dibenzyline prevented choleystokinetic activity of CCK-PZ and caerulein. It is considered that the preventing effect of dibenzyline may not be related with blocking effect of alph receptor.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/115777
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 박사
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