토끼 척출심방의 교감신경성 수용체에 관한 연구

Abstract

[한글]

교감신경성 반응은 표적장기의 세포막에 게재하는 α- 및 P-수용체의 활성에 의해 일어나며 그중 α-수용체 활성은 흥분을, β- 수용체 활성은 억압반응을 일으키나 심근에서는 β-수용체만 존재하면서 예외적으로 흥분반응을 나타낸다고 알려져 왔다.

그후 심근의 α-수용체의 존재에 관한 Wenzel 및 Su(1966)의 보고가 나오자 동물의 종류, 심장의 부위별로 그 존재를 확인하는 보고가 발표되었다. 그러나 주로 심근수축성 α-수용체에 대한 검색일 뿐 억압성 α-수용체에 대한 추구는 거의 없고 더구나 우심방 박동수에 관여하는 수용체의 존재여부는 보고된 바 없다.

한편 낮은 온도로 심근의 대사율을 변동시키면 α-수용체의 효과가 우세하여 진다는 주장도 있다. 그러므로 본 실험은 α-수용체의 반응을 잘 관찰할 수 있는 저온상태에서 시행하였으며, 자발적 수축운동을 나타내는 토끼의 우심방을 택하여 epinephrine 및 norepinephrine, 수종 α- 및 β-수용체 봉쇄약물을 적용, 상호 작용을 관찰하여 우심방의 α-수용체의 존재여부와 그 성상을 실험적으로 검토하고져 시행하였다.

실험결과를 요약하면 다음과 같다.

1. Epinephrine 혹은 norepinephrine에 의한 심방 박동수 증가효과는 α-수용체 봉쇄약물인 phentolamine 혹은 tolazoline 전처치로 항진되며, β-수용체 봉쇄약물인 acebutolol 전처치로 부분 봉쇄되나 α-수용체 봉쇄제를 동시 전처치하면 acebutolol의 억압효과가 경감되었다.

2. Epinephrine 혹은 norepinephrine에 의한 심근 수축력 증가효과도 심박동수에 대한효과와 유사한 양상으로 α-수용체 봉쇄약물 투여로 항진을 나타내며, acetutolol의 억압효과도 경감시켰다.

3. 영양액내 calcium농도를 증가시켜도 phentolamine의 효과는 변함없이 나타났다.

4. 저온 영양액내에서 자발운동이 억압된 심방은 norepinephrine 적용으로 심방운동이유발되고 acebutolol첨가로 심방운동의 점진적인 저하를, 계속 α-수용체 봉쇄약물의 첨가로 다시 심방운동의 항진을 나타냈다.

이상의 결과로 보아 저온 환경에서 토끼의 우심방에는 심방 수축운동뿐 아니라 박동운동을 억제하는 α-수용체가 존재한다고 인정하는 바이다.

[영문]

Adrenoceptors can be classified into two types, alpha or beta, according to their sensitivity to ahonists and antagnoists, and it has been known that the inotropic and chronotropic effects of catecholamines are primarily due to their effects on beta-adrenergic receptors. Wenzel and Su(1966), however, reported that the rat myocardium contained both alpha and beta receptors and Govier(1968) noted a similar suggestion in guinea pig atria. On the other hand, other authors reported contradictory experimental results that there is no evidence for the existance of alpha-adrenoceptors mediating positive inotropic effects in the ventricles of chicken (Benfey and Carolin,1971), of rat(Weston, 1671) and of dog(Kabela et at,, 1969).

Kunos and Szentivanyi (1968) suggested that availability of alpha- and beta-receptors can be changed by temperature and alpha-receptor is dominant at low temperature.

The present study wart undertaken to explore the presence and characteristics of alpha-adrenoceptor at low temperature (27℃) in right atria of rabbits where the existance of alpha-receptor is not demonstrated yet.

Adult rabbits of either sex, weighing approximately 2 kg were sacrificed by air embolism. The right atrium was carefully isolated and suspended in a muscle chamber containing 100ml of Tyrode solution. The solution was maintained at 27℃ and aerated with 95% O^^2 and 5% CO^^2. The atrium was attached to Grass force displacement transducer (FT. 03), and the rate and contractile force were recorded on a Grass model 7 Polygraph. After being attained a constant rate and contractility, experiment was begun.

The effects of alpha-blockers were observed on the rate and contratility, induced by epinephrine (E) and norepinephrine (NE) in the presence or absence of acebutolol. In case of silent atria at 27℃, NE was administered to initiate the atrial activity and then similar experimental protocols were performed.

The results obtained are summarized as follows:

1. Alpha-adrenergic: blockers, phentolamine or tolazoline(10**-4 M), potentiated the inotropic responses to E and NE at the concentration of 3×10**-6 M. The inotropic responses to E and NE were inhibited by beta-blocker acebutolol(10**-5 M), and this inhibition decreased by concomitant treatment of phentolamine or

tolazoline.

2. The chronotropic responses to E and NE were also potentiated and the inhibition decreased by concomitant treatment of phentolamine or tolaxoline.

3. Increase in calcium concentration to 5.1mM did not affect the effects of phentolamine (10**-4 M) on chronotropic and inotropic responses to NE(3×10**-6 M) and/or acebutolol(10**-5 M).

4. In silent atria sctivity initiated by NE(3×10**-6 M) reached plateay after 5 minutes. The NE-induced rate and contractility were depressed by acebutolol(10**-5 M), but the consecutive treatment of phentolamine, tolazoline or phenoxybenzamine(10**-6 M) cause no more depression and atrial activity was recovered slowly.

These results lead to a conclusion that in the right atrium of rabbit heart, there is an inhibitory alpha-adrenergic receptor on the rate and contractility and it is not affected by high concentration of external calcium.