Camostat 투여 흰쥐 이자 외분비선의 분비자극물질에 대한 반응성

Abstract

[한글]

고농도의 cholecystokinin(CCK)에 지속적으로 노출될 경우 이자외분비선의 성장, 효소단백함량 증가 등에 관하여는 잘 알려져 있으나, 이자 외분비선의 분비반응 변동, 특히 CCK나 caerulein, carbachol등의 분비자극물질로 자극했을 때의 반응성에 관하여는 논란이 많다.

본 실험에서는 내인성 CCK의 혈중농도를 증가시킨다고 알려진 camostat을 4일 또는 10일간 지속적으로 투여한 후 이자 조직을 적출, 분산 선세포(dispersed acini)를 분리하여 생체외에서 CCK 및 carbachol에 대한 amylase 유리 반응을 관찰하여 camostat 투여가 이

자 외분비선의 분비양상 및 분비자극물질에 대한 반응성에 어떤 영향을 미치는지 밝히고자 하였다. 실험결과를 요약하면 다음과 같다.

1. 최대효과를 나타내는 CCK의 농도는 대조군에 비해 Camostat 투여군이 높았으나 carbachol의 최대유효농도는 대조군과 camostat 투여군사이에 차이가 없었다.

2. 각 농도의 분비자극물질에 의한 효소유리반응을 최대반응에 대한 백분율로 나타낸 농도-반응 곡선에서 CCK 반응은 Camostat 투여로 오른쪽으로 이동하였지만 carbachol 반응은 별 차이가 없었다.

3. 각 농도에서의 효소유리반응을 직접 비교한 결과 CCK 10**-9 M 이상, carbachol 10**-6 M 이상 고농도의 분비자극물질에 대한 분비반응이 Camostat 투여군에서 높았으며 Camostat le일간 투여군에서 특히 높게 나타났다.

4. 조직내 amylase 활성치와 최대 amylase 유리 반응은 역상관 관계를 나타내었다.

이상의 결과로 보아 이자 외분비선에 대한 지속적인 내인성 CCK 자극은 외분비 효소 분비에 있어 분비자극물질, 특히 고농도의 CCK에 대한 반응성 을 항진시킨다고 생각된다.

Exocrine secretory responsiveness of dispersed pancreatic acini to secretagogues in

camostat-treated rats

Chul Kim

Department of Medical Science The Graduate School, Yonsei University

(Directed by Professor Kyung Hwan Kim)

It is well known that chronic stimulation with CCK gives rise to growth of

exocrine pancreas and to increased content of enzyme proteins in pancreas. However,

little is known about changes of the secretory function of exocrine pancreas which

has been chronically stimulated with CCK, especially about the responsiveness to

secretagogues such as CCK, caerulein and carbachol.

The present study was performed to investigate the effect of camostat on

secretory profiles and the responsiveness to secretagogues of exocrine pancreas by

observing in vitro amylase release stimulated by cholecystokinin-octapeptide(CCK-8)

and carbachol in dispersed isolated pancreatic acini from camostat-treated rats for

4 or 10 days.

The results summarized as follows:

1. The maximal effective concentraion of CCK-8 in amylase release in the

camostat-treated group was greater than control group, but that of carbachol was

not different between groups.

2. Analysis of the stimulated amylase release as the percentage of the maximal

response revealed that camostat treatment caused right-shift of the dose-response

curve of CCK-8. Camostat did net cause significant changes in the dose-response

curve of carbachol.

3. There were considerable increases in the amylase release in the

camostat-treated group, compared to the control when acini were stimulated with

CCK-8 10**-9 M and carbaochol 10**-6 M, and higher concentrations.

4. There was a reverse correlation between the tissue content and the maximal

release (percent of the total content) of amylase.

These results suggest that chronic exposure of exocrine pancreas to increased

endogenous CCK can enhance the responsiveness of exocrine enzyme secretion to

secretagogues, especially at higher concentrations of CCK and carbachol.

[영문]

It is well known that chronic stimulation with CCK gives rise to growth of exocrine pancreas and to increased content of enzyme proteins in pancreas. However, little is known about changes of the secretory function of exocrine pancreas which has been chronically stimulated with CCK, especially about the responsiveness to secretagogues such as CCK, caerulein and carbachol.

The present study was performed to investigate the effect of camostat on secretory profiles and the responsiveness to secretagogues of exocrine pancreas by observing in vitro amylase release stimulated by cholecystokinin-octapeptide(CCK-8)

and carbachol in dispersed isolated pancreatic acini from camostat-treated rats for 4 or 10 days.

The results summarized as follows:

1. The maximal effective concentraion of CCK-8 in amylase release in the camostat-treated group was greater than control group, but that of carbachol was not different between groups.

2. Analysis of the stimulated amylase release as the percentage of the maximal response revealed that camostat treatment caused right-shift of the dose-response curve of CCK-8. Camostat did net cause significant changes in the dose-response curve of carbachol.

3. There were considerable increases in the amylase release in the camostat-treated group, compared to the control when acini were stimulated with CCK-8 10**-9 M and carbaochol 10**-6 M, and higher concentrations.

4. There was a reverse correlation between the tissue content and the maximal release (percent of the total content) of amylase.

These results suggest that chronic exposure of exocrine pancreas to increased endogenous CCK can enhance the responsiveness of exocrine enzyme secretion to secretagogues, especially at higher concentrations of CCK and carbachol.