위운동에 대한 glucagon의 영향

Abstract

[한글]

위장 홀몬중 glucagon은 cholecystokinin, secretin, vasoactive intestinal polypeptide 및 gastric inhibitory polypeptide등과 같이 위운동을 억제시킨다고 알려져 있다.

Glucagon의 위운동 억제기전은 확실히 규명되어 있지 않으나 일찍부터 glucagon의 대사효과인 고혈당과는 무관하다고 생각하여 왔다. 현재 glucagon투여후 나타나는 혈중 catecholamine농도의 증가 또는 미주신경 전달억제등으로 위운동이 감소한다는 주장과 gastrin과의 길항작용에 기인한다는 보고등 기전에 대한 설명이 많으나 아직 확실치는 않다.

최근 glucagon의 대사성 효과가 주로 cyclic AMP에 의함을 주목하여 위운동에 대한 작용도 cyclic AMP가 중요한 역할을 할 것이라고 추측하나 아직 의견이 구구하다.

이번 실험에서는 토끼의 위절편을 사용하여 glucagon의 위평활근 이환효과를 검색하여 다음과 같은 결론을 얻었다.

1. Glucagon은 휴식기 위절편에서나 bethanechol유발 수축절편에서 모두 이완효과를 나타내었고 이때 pD^^2치는 각각 6.30±0.05, 6.25±0.06으로 비슷하였다.

2. Carbachol과 bethanechol은 용량에 비례하여 위절편의 긴장도를 증가시켰으며 이때 pD^^2치는 5.92±0.11 및 4.90±0.11이었고 glucagon 10**-6M 전처치로도 pD^^2치 및 최대효능치는 변동되지 않았다.

3. Glucagon전처치는 histamine외 최대효능치를 56% 감소시켰다.

4. Glucagon전처치로 pentagastrin 및 barium chloride에 의한 긴장도 증가는 억제되었다.

5. Glucagon이완효과는 phentolamine 또는 propranolol전처치로 봉쇄되지 않았다.

6. 위절편에서 bethanechol수축반응에 대한 glucagon의 pD^^2치는 6.25±0.06이었으나 theophylline 또는 papaverine을 전처치함으로 glucagon의 이완효과가 증대되었으며 이 상협작용은 papaverine전처치시에 더 강하게 나타났다.

7. 칼슘배제 고칼륨 영양액내에서 칼슘 재투여에 의한 위절편의 긴장도 증가는 glucagon전처치로 변동되지 않았다.

이상의 실험결과로 glucagon은 토끼 위평활근에 대해 휴식기뿐아니라 histamine 및 pentagastrin유발 수축작용을 억압하며 또한 theophylline 또는 papaverine과 상승효과를 나타냄으로 보아 glucagon의 위평활근 이완효과에는 Ca**++ influx 보다는 glucagon으로 인한 세포내 cyclic AMP증가가 관련된다고 생각한다.

[영문]

It has been known that glucagon inhibited the gastric contraction induced by hunger. Glucagon has been used clinically as a relaxant in gastroacopy, sigmoidoscopy and bronchoscopy.

While the metabolic effects of blucagon have been studied extensively, the mechanism of this spasmolytic affects of glucagon has not been well studies. The increase of blood catecholamine or the inhibition of vagal transmission by glucagon was suggested as possible mechanisms involved in the spasmolytic action. Alternatively, the glucagon induced increase of cyclic AMP was proposed as a major mechanism involved in the spasmolytic effect of glucagon.

Therefore, the present study has been carried out to investigate the mechanism of spasmolytic activity of glucagon employing the stomach strips in rabbits.

The obtained results are as follows:

1. Glucagon had relaxing effect on both resting tension and bethanechol-induced contraction of isolated stomach strips of rabbit in a dose dependent manner and the calculated pD^^2 values were 6.30±0.05 and 6.25±0.06 at resting state and bethanechol-induced contraction, respectively.

2. Addition of carbachol or bethanechol showed dose dependent increase in the tension of stomach strips and their pD^^2 values were 5.92±0.11 and 4.90±0.11, respectively. Pretreatment of glucagon 10**-6 M changed neither the calculated pD^^2 values nor the maximal efficacies of carbachol and bethanechol.

3. Pretreatment of the stomach strip wish glucagon showed 56% reduction in the maximal efficacy of histamine induced contraction without much change in the calculated pD^^2 values in isolated stomach strips.

4. Glucagon tended to inhibit the development of tension inducible with pentagastrin and barium chloride.

5. Relaxing effects of glucagon were not blocked by the pretreatment of stomach strips with phentolamine(10**-5 M) or propranolol(10**-5 M), or both.

6. The pD^^2 value of glucagon was increased to 6.43±0.10 and 6.76±0.13(p<0.05) by pretreatment of stomach strips with theophylline(3×10**-5 M) and papaverine(3×10**-6 M).

7. Pretreatment of the stomach stripe with glucagon did not inhibit the calcium induced contraction of rabbit stomach strip which was in the calcium free, high potassium depolarizing solution.

These results have demonstrated that glucagon relaxes stomach strips isolated from rabbit and antagonizes the contractile response inducible with histamine, pentagastrin and barium chloride. Further results obtained with theophylline and papaverine have suggested that the spasmolytic actions of glucagon on stomach strips may be mediated via increase of cyclic AMP levels.