담낭의 담즙배제기전에 관한 실험적 연구

Abstract

[한글]

Experimental Studies on the Mechanism of Gall Bladder Evacuation

Sa Suk Hong, M.D.

Department of Pharmacology and Toxicology

Yonsei University Medical College Seoul, Korea

Since Meltzer proposed a hypothesis on the mechanism of gall bladder contraction

and evacuation in 1917, much attention on the physiology of the gall bladder have

been attracted. Meltzer suggested, first, that inasmuch as the sphincter of Oddi

must relax when the gall bladder contracts if the bile is to be extruded into the

duodenum, the activities of these two parts of the biliary tract must be

co-ordinated and under the control of the law of contrary innervation. Second, of

this be true, magnesium sulfate applied to the sphincter might produce relaxation

there and at the same time contraction of the gall bladder : third, magnesium

sulfate might be injected into the duodenum for the treatment of jaundice and

biliary colic. However, subsequent studies by other investigators (Sosman et al.,

1925 : Berg and Jobling, 1927) failed to prove this hypothesis except for the last

suggestion which survived as a clinical interest of "gall bladder drainage".

Considering the conflicting reports on the relationship between the gall bladder

and the Odd's sphincter, it appears to be fruitful to determine whether or not the

contraction of the gall bladder may be associated with a relaxation of the

sphincter of the common duct. In a study of cross-circulation experiment, Ivy and

Oldberg (1927 : 1928) found that a certain substance may formed in the duodenum of

one dog and could influence the activity of the gall bladder of the other animal.

They maned this substance "cholecyetokinin" and prepared it from the mucosal

extracts of the duodenum. The intravenous injection of this substance was found to

duplicate the gall bladder contracting activity of a fat-containing meal. The

discovery of cholecystokinin brought a great advance on the physiology of gall

bladder thereafter. Sandblom, Voegtlin and Ivy (1935) reported that

cholecystokinin-containing extracts produce relaxation of the sphincter of Oddi on

the anesthetized dogs. However, in view of the fact that cholecystokinin causes

contraction of the intestinal muscle, further experiments would be meeded to

determine the activity of cholecystokinin on the sphincter of Oddi.

In the present experiments, a procedure has been devised to record continuously

the pressure in the biliary tracts of conscious dogs. Employing this procedure, the

releasing mechanism of cholecystokinin from the Thiry-Vells loops of duodenum has

been examined.

Summary and Conclusion

1. Dogs have been prepared with a Thiry-Vells loop of the duodenum and also with

a small tube inserted either into the common bile duct or into the gall bladder.

The resting biliary pressure in the conscious dogs placed in a stock was about 20

cm H^^2 O.

2. Irrigation of the Thiry-Vella loop with N/20 HCL regularly prodeced an

increase in the biliary pressure after a latent period 2-3 minutes. The biliary

pressure usually returned to the pre-irrigation level within 10 minutes and the

returning was faster if the loop was washed out with physiological saline.

3. The intravenous injection of cholecystokinin-containing

extract(histamine-free) duplicated the increase in the biliary pressure due to the

irrigation with HCl of the Thiry-Vella loops. However, the former produced the

pressure response without the latent period.

4. In most conscious dogs studied, the irrigation of the loop with milk, 5%

peptone, corn oil, protein hydrolysate, 5% solution of essential amino acids or

cleic acid increased the biliary pressure. On the other hand, the irrigation with

10% glucose or sucrose, 2% acetic acid or 2% sodium bicarbonate was without effect.

5. The intravenous injection of adrenaline or acetylcholine produced no changes

but amyl nitrite or nitroglycerine caused a decrease in the biliary pressure.

6. The psychic effects due to the taste and small of food resulted a transitory

increase in the biliary pressure.

7. The response to the irrigation with HCl of the Thiry-Vella loop in the aminals

with an occluded common duct was much greater and more prolonged than that in the

same or different animals with a patent duct. Opening of papilla in

choledocho-duodenal junction was observed when the biliary prossure increased in

the anesthetized dog with pentobarbital sodium.

8. The local administration of 2% procaine into the Thiry-Vella loop prevented

the biliary pressure response to the irragation with HCl but failed to prevent the

increase in biliary pressure following the intravenous injection of

cholecystokinin. The intravenous injection of porcaine was not able to prevent the

pressure response to the irrigation of the loop with HCl.

9. Hexanethonium chloride produced a drop in the biliary pressure by itself and

prevented the pressure response to either the irrigation with HCl or feeding even

in the animal with an occluded duct. However, it had no effects on the response to

the intravenous injection of cholecystokinin.

10. Atropine produced no decrease but rather an enhancement of the response to

the irrigation of the Thiry-Vella loop with HCl in the animals with occluded common

ducts.

11. The results obtained in anesthetized dogs with pentobarbital sodium were

qualitatively similar to those observed in the conscious animals. But the intensity

of the response in the former was much weaker than that in the latter.

12. These results lead to the conclusion that substance causing release of

cholecystokinin from the duodenum do so by causing stimulation of a

procaine-sensitive receptors which are connected to the cells producing

cholecystokinin by pathway which can be blocked by nexamethonium. It is considered

that the receptor and pathway are most likely nervous.

[영문]

Since Meltzer proposed a hypothesis on the mechanism of gall bladder contraction and evacuation in 1917, much attention on the physiology of the gall bladder have been attracted. Meltzer suggested, first, that inasmuch as the sphincter of Oddi must relax when the gall bladder contracts if the bile is to be extruded into the duodenum, the activities of these two parts of the biliary tract must be co-ordinated and under the control of the law of contrary innervation. Second, of this be true, magnesium sulfate applied to the sphincter might produce relaxation there and at the same time contraction of the gall bladder : third, magnesium sulfate might be injected into the duodenum for the treatment of jaundice and biliary colic. However, subsequent studies by other investigators (Sosman et al., 1925 : Berg and Jobling, 1927) failed to prove this hypothesis except for the last suggestion which survived as a clinical interest of "gall bladder drainage".

Considering the conflicting reports on the relationship between the gall bladder and the Odd's sphincter, it appears to be fruitful to determine whether or not the contraction of the gall bladder may be associated with a relaxation of the sphincter of the common duct. In a study of cross-circulation experiment, Ivy and Oldberg (1927 : 1928) found that a certain substance may formed in the duodenum of one dog and could influence the activity of the gall bladder of the other animal.

They maned this substance "cholecyetokinin" and prepared it from the mucosal extracts of the duodenum. The intravenous injection of this substance was found to duplicate the gall bladder contracting activity of a fat-containing meal. The discovery of cholecystokinin brought a great advance on the physiology of gall

bladder thereafter. Sandblom, Voegtlin and Ivy (1935) reported that cholecystokinin-containing extracts produce relaxation of the sphincter of Oddi on the anesthetized dogs. However, in view of the fact that cholecystokinin causes contraction of the intestinal muscle, further experiments would be meeded to

determine the activity of cholecystokinin on the sphincter of Oddi.

In the present experiments, a procedure has been devised to record continuously the pressure in the biliary tracts of conscious dogs. Employing this procedure, the releasing mechanism of cholecystokinin from the Thiry-Vells loops of duodenum has

been examined.

Summary and Conclusion

1. Dogs have been prepared with a Thiry-Vells loop of the duodenum and also with a small tube inserted either into the common bile duct or into the gall bladder.

The resting biliary pressure in the conscious dogs placed in a stock was about 20 cm H^^2 O.

2. Irrigation of the Thiry-Vella loop with N/20 HCL regularly prodeced an increase in the biliary pressure after a latent period 2-3 minutes. The biliary pressure usually returned to the pre-irrigation level within 10 minutes and the returning was faster if the loop was washed out with physiological saline.

3. The intravenous injection of cholecystokinin-containing

extract(histamine-free) duplicated the increase in the biliary pressure due to the irrigation with HCl of the Thiry-Vella loops. However, the former produced the pressure response without the latent period.

4. In most conscious dogs studied, the irrigation of the loop with milk, 5% peptone, corn oil, protein hydrolysate, 5% solution of essential amino acids or cleic acid increased the biliary pressure. On the other hand, the irrigation with 10% glucose or sucrose, 2% acetic acid or 2% sodium bicarbonate was without effect.

5. The intravenous injection of adrenaline or acetylcholine produced no changes but amyl nitrite or nitroglycerine caused a decrease in the biliary pressure.

6. The psychic effects due to the taste and small of food resulted a transitory increase in the biliary pressure.

7. The response to the irrigation with HCl of the Thiry-Vella loop in the aminals with an occluded common duct was much greater and more prolonged than that in the same or different animals with a patent duct. Opening of papilla in choledocho-duodenal junction was observed when the biliary prossure increased in

the anesthetized dog with pentobarbital sodium.

8. The local administration of 2% procaine into the Thiry-Vella loop prevented the biliary pressure response to the irragation with HCl but failed to prevent the increase in biliary pressure following the intravenous injection of cholecystokinin. The intravenous injection of porcaine was not able to prevent the

pressure response to the irrigation of the loop with HCl.

9. Hexanethonium chloride produced a drop in the biliary pressure by itself and prevented the pressure response to either the irrigation with HCl or feeding even in the animal with an occluded duct. However, it had no effects on the response to

the intravenous injection of cholecystokinin.

10. Atropine produced no decrease but rather an enhancement of the response to the irrigation of the Thiry-Vella loop with HCl in the animals with occluded common ducts.

11. The results obtained in anesthetized dogs with pentobarbital sodium were qualitatively similar to those observed in the conscious animals. But the intensity of the response in the former was much weaker than that in the latter.

12. These results lead to the conclusion that substance causing release of cholecystokinin from the duodenum do so by causing stimulation of a procaine-sensitive receptors which are connected to the cells producing cholecystokinin by pathway which can be blocked by nexamethonium. It is considered that the receptor and pathway are most likely nervous.