단백질 대사에 대한 몰핀의 이화 작용

Abstract

[한글]

몰핀이 1985년 포유동물의 조직에서 발견되고 생체내 합성이 증명되면서 내인성 몰핀도 내인성 아편계 펠타이드인 β-endorphin과 마찬가지로 외상이나 수술 후의 생체 항상성에 중요한 역할을 하는 것으로 여겨지고 있다. 생체 항상성에 있어 단백질 대사가 중요한 부분을 차지하고 있으나 현재까지 대사에 대한 몰핀의 영향은 주로 당대사에 집중되어 있을 뿐 단백질 대사에 미치는 영향은 거의 연구된 바가 없다. 본 연구에서는 몰핀 주입에 의한 아미노산의 대사변화와, 이에 관련된 각 홀몬의 변화를 알아봄으로써 몰핀에 의한 아미노산 대사 변화의 기전을 알아보고자 하였다.

실험동물로는 잡종개 11마리를 사용하여 한 군에서는 몰핀을 정맥내로 주입하고 다른 한 군에서는 뇌실내로 주입하여 각각 당과 leucine의 대사, insulin, cortisol, catecholamine 등의 홀몬을 측정하여 다음과 같은 결과를 얻었다.

1. 몰핀은 혈액에서 뇌척수액으로의 이동은 15% 정도 일어나나 뇌척수액에서 혈액으로의 이동은 없었다.

2. 몰핀 주입에 의한 당대사의 변화는 정맥내 주입시 보다 뇌실내 주입시에 더 급격한 변동을 보이며, 이때 간에서의 당 평형상태가 의의있게 증가하였다.

3. 몰핀의 뇌실내 주입시에 leucine 농도가 증가하며, 이때 간에서의 leucine 평형상태가 의의있게 증가하였다. 정맥내 주입시에는 leucine 농도는 감소하나 장관내 leucine 평형상태는 변동이 없었다.

4. 몰핀을 주입 후에 혈중 cortisol 및 catecholamine의 농도가 증가하며, 정맥내 주입시 보다 뇌실내 주입시 더 많이 증가하였다.

5. 몰핀의 정맥내 주입시에는 insulin 분비가 증가하는 반면, 뇌실내 주입시에는 혈당이 더 증가함에도 불구하고 insulin 분비는 억제되었다.

이상의 결과로 보아 몰핀은 교감신경계와 뇌하수체-부신축의 활성화로 인한 스트레스 홀몬의 증가와 더불어 insulin 분비 억제에 의해 단백질의 이화효과를 나타내며 이는 말초성이 아니라 중추성 효과에 의한 것으로 생각된다.

Catabolic effect of morphine on protein metabolism

Koo Young Jung

Department of Medical Science, The Graduate School, Yonsei University

(Directed by Professor Young Soo Ahn)

In 1985, morphine was isolated from several mammalian tissues, and its endogenous

synthetic pathway has been discovered to be the same in plants such as the poppy

(Papaver somniferum). Endogenous morphine is supposed to have a certain role in

homeostasis after trauma and severe illness as β-endorphin, an endogenous opioid

peptide, does. Protein metabolism is one of the key components in the homeostasis.

However, most studies about the effect of morphine on metabolism has been focused

on the glucose metabolism. The purpose of this study is to investigate the

mechanism of catabolic effect of morphine on the protein metabolism by analyzing

protein metabolism and the levels of catabolic hormones after exogenous morphine

administration.

Morphine was infused intravenousely to one group of mongrel dogs, and

intracerebroventricularly to another group. The glucose and leucine concentration

and splanchnic balance were analyzed in each dog, and insulin, cortisol, and

catecholamines were assayed. The following results were obtained.

1. About 15% of the infused morphine passed through the blood-brain-barrier from

plasma to cerebrospinal fluid, but there was no appreciable movement from

cerebrospinal fluid to plasma.

2. After intra cerebroventricular infusion of morphine, it was noticed that the

increase of glucose concentration was more prominant than after intravenous

infusion in the early phase. At the same time hepatic and splanchnic g1ucose

balance was significantly increased in intracerebroventricular infusion group.

3. Intracerebroventricular infusion of morphine increased the concentration of

plasma leucine with increasing the hepatic and splanchnic leucine balance. But

intravenous infusion decreased the plasma leucine concentration without any

significant chanties of hepatic and splanchnic leucine balance.

4. The increases of cortisol and catecholamines were more prominent after

intracerebroventricular infusion than intravenous infusion.

5. While the plasma insulin concentration was increased after intravenous

infusion of morphine, it was not increased after intracerebroventricular infusion

despite of higher blood glucose concentration.

These results suggest that morphine has catabolic effect on protein metabolism by

suppressing the secretion of insulin as well as by increasing the stress hormones

via activating the sympathetic nervous system and pituitary-adrenal axis. This

effect is supposed to be mediated by contract opioid system, not peripheral.

[영문]

In 1985, morphine was isolated from several mammalian tissues, and its endogenous synthetic pathway has been discovered to be the same in plants such as the poppy m(Papaver somniferum). Endogenous morphine is supposed to have a certain role in homeostasis after trauma and severe illness as β-endorphin, an endogenous opioid peptide, does. Protein metabolism is one of the key components in the homeostasis.

However, most studies about the effect of morphine on metabolism has been focused on the glucose metabolism. The purpose of this study is to investigate the mechanism of catabolic effect of morphine on the protein metabolism by analyzing protein metabolism and the levels of catabolic hormones after exogenous morphine administration.

Morphine was infused intravenousely to one group of mongrel dogs, and intracerebroventricularly to another group. The glucose and leucine concentration and splanchnic balance were analyzed in each dog, and insulin, cortisol, and catecholamines were assayed. The following results were obtained.

1. About 15% of the infused morphine passed through the blood-brain-barrier from plasma to cerebrospinal fluid, but there was no appreciable movement from cerebrospinal fluid to plasma.

2. After intra cerebroventricular infusion of morphine, it was noticed that the increase of glucose concentration was more prominant than after intravenous infusion in the early phase. At the same time hepatic and splanchnic g1ucose balance was significantly increased in intracerebroventricular infusion group.

3. Intracerebroventricular infusion of morphine increased the concentration of plasma leucine with increasing the hepatic and splanchnic leucine balance. But intravenous infusion decreased the plasma leucine concentration without any significant chanties of hepatic and splanchnic leucine balance.

4. The increases of cortisol and catecholamines were more prominent after intracerebroventricular infusion than intravenous infusion.

5. While the plasma insulin concentration was increased after intravenous infusion of morphine, it was not increased after intracerebroventricular infusion despite of higher blood glucose concentration.

These results suggest that morphine has catabolic effect on protein metabolism by suppressing the secretion of insulin as well as by increasing the stress hormones via activating the sympathetic nervous system and pituitary-adrenal axis. This

effect is supposed to be mediated by contract opioid system, not peripheral.