Abstract
The effects of external $Ca^{2+}$ ana the inhibition of Na-pump on vanadate-induced contraction in isolated human and rat uterine smooth muscle were studied and the following results were observed. 1) Vanadate induced contraction in rat uterine muscle and showed maximal contraction at concentration of $5{\times}10^{-4}$M, and the contractile response to vanadate was more sensitive in human than rat uterine muscle. 2) Vanadate-induced contraction was not completely inhibited by $Ca^{2+}$ removal from PSS and the response to $Ca^{2+}$ removal was more sensitive in human than rat uterine muscle. 3) Vanadate-induced contraction decreased with increasing concentration of verapamil, but even in the presence of $3{\times}10^{-5}M$ verapamil which inhibited 100 K-induced contraction completely. about 40% of maximal contraction remained, and its amplitude was similar to that of contraction in $Ca^{2+}$-free solution. 4) Vanadate-induced contraction was increased by the inhibition of Na-pump and this increase also could be observed in the presence of $3{\times}10^{-5}M$ verapamil. 5) After pretreatment with $Ca^{2+}$-free PSS containing ouabain Vanadate-induced contraction was not increased, but the contractile response of these tissues to the addition of external $Ca^{2+}$ was remarkably increased in the presence of vanadate. 6) $3{\times}10^{-5}$M verapamil inhibited vanadate-induced $Ca^{45}$ influx completely, but after pretreatment with ouabain vanadate could induce remarkable $Ca^{45}$ influx even in the presence of verapmil. 7) With increasing the time of pretreatment with ouabain or $K^+$-free solution, the degree of increase in contraction by vanadate was more remarkable. 8) $10^{-4}M$ papaverine stowed a considerable inhibition of the increase in the vanadate-induced contraction by pretreatment with ouabain. 9) Acetylcholine-induced contraction increased with lengthening the duration of Na-pump inhibition even in the presence of verapamil. Considering above results it seems that the uterine muscle of human is more sensitive to vanadate than that of rat, and both internal and external $Ca^{2+}$ is utilized in vanadate·induced contraction. In the case of Na-pump inhibition several smooth muscle contracting agents seems to induce $Ca^{2+}$ influx which is not inhibited by verapamil. This $Ca^{2+}$ influx seems to be inhibited by papaverine and to be associated with membrane potential, although its precise characteristics is not certain.
Vanadate의 수축에 이용되는 $Ca^{2+}$의 동원 경로와 Na-Pump억제가 vanadate의 수축에 어떤 영향을 미치는 지를 밝히기 위해 본 실험을 시행하여 다음과 같은 곁과를 얻었다. 1) 흰쥐의 자궁근에서는 vanadate는 수축을 일으켜 $5{\times}10^{-4}M$에서 최대수축을 나타내었으며 사람의 자궁근이 흰쥐의 자중근에 비해 vanadate에 더 민감한 반응을 보였다. 2) Vanadate에 의한 수축은 $Ca^{2+}$제거에 의해 완전히 억제되지 않았고 사람의 자궁근이 외부 $Ca^{2+}$의 농도변화에 더 민감한 반응을 보였다. 3) Vanadate에 의한 수축은 verapamil농도를 증가시킴에 따 억제되었으며 100k에 극한 수축을 완전 억제시키는$3{\times}10^{-5}M$ verapamil 존재하에서도 최대수의 40%정도가 남아있었고, 이 크기는 $Ca^{2+}$없는 용액에서의 수축의 크기와 유사하였다. 4) Na-pump억제시 vanadate의 수축은 증가하였고 이 현상은 $3{\times}10^{-5}M$ verapamil 존재하에서도 나타났다. 5) $Ca^{2+}$없는 ouabain용액에서 전처치후에 vanadate에 의한 수축은 증가하지 않았으나 외부내 $Ca^{2+}$을 부가할 나타나는 반음은 대조군에 비해 현저히 증가하였다. 6) Verapamil 존재시 vanadate에 의한 $Ca^{45}$유입은 완전히 억제되었으나 ouabain으로 처리한 후는 verapamil 존재하에서도 vanadate가 현저히 $Ca^{45}$유입을 일으켰다. 7) Ouabain이나 K 없는 용액으로 치리시간이 증가함에 따라 vanadate에 의한 수축의 증가정도는 더욱 더 현저하였다. 8) Ouabain 전처치시 증가된 vanadate에 의한 수축은 $10^{-4}M$ papaverine에 의해 현저히 억제되었다. 9) Acetylcholine에 의한 수축은 verapamil 존재하에서도 Na-pump억제 시간이 증가함에 따라 증가하였다. 이상의 결과로 볼 때 vanadate에 대해 사람의 자궁근이 흰쥐의 자궁근에 비해 더 민감한 반응을 보이고 vanadate에 의한 수축에는 외부와 내부 $Ca^{2+}$이 모두 이용되며 Na-pump 억제시 여러가지 근수축물질이 verapamil에 의해 억제되지 않는 $Ca^{2+}$유입을 일으키며 이 유입경로의 성질은 확실히 알 수 없으나 Papaverine에 의해 억제되며 막전위의 변화와 관련이 있는 것으로 생각된다.
(Department of Physiology, College of Medicine, Pusan National University)
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